Combine PDF

1) In human at the end of meiosis I how many chromosomes and how many chromatids are
present per cell? 23 46
2) In human at the end of meiosis II how many chromosomes and how many chromatids are
present per cell? 23 23
3) At what stage of meiosis does segregation of alleles take place? Explain! In meiosis 2
4) Where and when does homologous recombination take place in sexually reproducing
organisms? What is its observable morphological appearance? In nucleus when prophase
in chromosomes
5) Describe the Meselson and Stahl experiment. What does it prove? Prove the DNA semi-
conservative replication. The E coil was grown for several generations in N15 condition.
When they are all contains N15 nitrogen we replicate it in N14 condition. Than they
observed the newly established DNA’s strand posses different nitrogen element
6) What does semiconservative replication mean?
7) Describe the Hershey-Chase experiment. What was demonstrated by the experiment?

The inheritance substance of virus is DNA not proteins
8) Which DNA bases are pyrimidines and which are purines? Adenine Urine Guanine are
purines
9) Describe the role of telomerase in telomere formation. It is an enzyme that can extend the
telomeres of chromosomes
10) The thymine found in DNA is replaced in RNA by the closely related pyrimidine
______Adenine____.
11) According to Chargaff's rules, the amount of guanine in double-stranded DNA molecule
equals that of _____________, and the amount of thymine is the same as that of
_____________.
12) DNA strands are said to be _________ because the phosphate linkages in the backbones
run in opposite directions.
13) The chemical bonds in DNA, by which the sugar components of adjacent nucleotides are
linked through the phosphate groups, are called ____phosphediester________.
14) What are the three essential attributes that a biological molecule would need to be a
useful genetic material?
15) If a DNA has a guanine content of 23% and an adenine content of 27%, what is the
content of the other two bases?
16) Why were 32P and 35S ideal radioactive tracers in the experiments performed by
Hershey and Chase? Would 14C and 3H be suitable radioactive isotopes for these
experiments? Because phosphorus group exist in DNA but no amino acids.
17) Describe some of the key differences between and RNA and DNA. Sugar deoxyribose
and sugar ribose. Different functions. AUCG and ATCG
18) When Avery and his colleagues obtained a semi-purified DNA preparation from S-type
cells, they treated this material with proteases, , and DNase before assaying for
transforming activity. What was the purpose and result of these experiments?
19) Chromosomes that pair in meiosis and have the same genetic loci and structure are said to
be _______homozygous_________.
20) X and Y chromosomes are called sex chromosomes to distinguish them from the other
pairs of chromosomes, which are called ____autosome____________.
21) The pairing of homologous chromosomes during meiosis is known as

____synapses___________.
22) Differentiate between the behavior of chromosomes in metaphase of mitosis and meiosis
I.
23) How did the Meselson-Stahl experiment proved semiconservative replication of DNA?
24) What was the ratio of the different DNA molecules after 1, 2 and 3 rounds of replication
on 14N medium in the Meselson Stahl experiment?
25) Replication of which DNA molecules can be described by the θ (theta model) Describe
the experiment proving this model. Replication proceeds around the circle in both
direction from the origin. Replication is bidirectional. Found in E coli.
26) What do you mean by rolling circle replication. Illustrate your answer with a drawing.
Replication is initiated by a break in one of the nucleotide strands. DNA synthesis begins
at the 3' end of the broken strand; the inner strand is used as a template. The 5' end of the
broken strand is displaced. It takes place in some viruses and in the F factor of E. coli.
27) How many replicons are there on a eukaryotic chromosome and on a bacterial
chromosome? Explain.
28) Name at least 5 proteins, which are needed to carry out DNA replication. Describe their
function, as well. DNA polymerase which catalyzes the joining of deoxyribonucleoside
5′-triphosphates (dNTPs) to form the growing DNA chain. DNA Helicase, Helicase
separates the two strands of DNA at the Replication Fork behind the topoisomerase. DNA
Ligase. Re-anneals the semi-conservative strands and joins Okazaki Fragments of the
lagging strand. Topoisomerase. Relaxes the DNA from its super-coiled nature. Primase.
Provides a starting point of RNA (or DNA) for DNA polymerase to begin synthesis of the
new DNA strand.
29) Name the two strands that are being synthesized at the replication fork. How are they
synthesized and in which direction? Leading strand and lagging strand. 3 to 5
30) Which enzyme is indispensable for the initiation of DNA synthesis? What is the chemical
nature of its product? Primase. Primer
31) DNA polymerases engaged in replication possess an important second activity. What is
the name and significance of this activity?
32) Describe the function of gyrase, helicase, primase and DNA ligase enzymes.
33) DNA polymerases are utilized in the methods of molecular biology. Describe at least 3
important methods that use these enzymes.
34) Which enzymes can specifically cleave DNA molecules? Give the name and significance
of these enzymes. Restriction enzymes 1 to 5 type. It cleaves the DNA strand in specific
nucleotide sequences.
35) How can you amplify a single DNA molecule billionfold? What is the name of this
method and what are the main steps in it?
36) Can you use polymerase chain reaction to amplify a gene if you do not have any
information about its nucleotide sequence? Explain!
37) What is the function of the 3’-to-5’ exonuclease activity associated with the DNA
polymerase, and what are the consequences for the cell if this function is inactivated by
mutation?
38) What chemical groups are joined by DNA ligase? By DNA polymerase? Phosphodiester
triphosphate.
39) What is meant by the statement that the replication fork is asymmetrical?
40) An asteroid probe brings back a bacterial species that has DNA as its genetic material.
You perform a Meselson Stahl experimentand show that, after one round of replication in
14
N medium , half of the daughter DNA duplexes have 15N in both strands whereas the
other half have 14N in both strands. Interpret these data.
41) The double strand break model is the latest one explaining molecular mechanism of
recombination. What experimental results led to this model, involving heteroduplex
formation between the participating DNA molecules?
42) Which is the main protein of general recombination? Describe its activity.
43) Characterize site-specific recombination and mention at least one concrete example.
1) Because many eukaryotic genes contain ________intron____________ that are present in
the primary transcripts but removed from the mature mRNA, the cDNA sequence is not
identical with the genomic DNA.
2) What are enhancers, how are they positioned related to the regulated genes and how do
they act? They are a segment of DNA that can bind to trans-acting factor proteins. They
can positioned in the upstream or downstream of DNA. Gene transcription will be
strengthened.
3) What is the role of amino acyl-tRNA synthetases in the process of translation? It will
bind the correct amino acids to tRNA
4) Why is it important that excision of introns be precise to the level of a single

nucleotide?Mutation of the corresponding bases in the DNA can result in mis-splicing,
either failure to remove an intron or removal of an exon along with the adjacent intron
5) How can you explain the contradiction that humans have about 25.000 genes and 100.000
different proteins? The alternative splicing. From one gene, several proteins can be
constructed depending on which introns are spliced. Structure of proteins. Proteins may
fold (to what we call primary, secondary, tertiary and quaternary structures) differently in
different environment
In prokaryotic cells one gene (cistron) determines one protein (polypeptide). Is this also true
and characteristic for eukaryotic cells? No. We have approximately 25000genes but we have
100000proteins.
6) How does the possibility of alternative splicing affect the generality of the statement that
one gene encodes one polypeptide chain? One gene faces a lot of protein.
7) How does cDNA differ from the eukaryotic genomic coding sequence? Because they
came from the retrotransportation from mRNA, so they lack of introns.
8) Please describe the exon shuffle model. Exon shuffle is a mechanism for the formation of
new genes. It is process through which two or more exons from different gene can be
brought together or the same exon can be duplicated.
9) ___RNA polymerase__3___________ transcribes all tRNA genes and the 5S component

of rRNA.
10) RNA polymerase _______2___________ is responsible for transcribing all protein-

coding genes.
11) In eukaryotes, RNA polymerase _________1_________ is used exclusively in producing

the transcript that becomes processed into ribosomal RNA.
12) The site of RNA polymerase binding to the DNA template is called the
_____promoter__________.
13) RNA splicing takes place in nuclear particles, composed of protein and several
specialized small RNA molecules, known as ______snRNP____________.
14) The 3' termini of eukaryotic mRNA molecules are usually modified by the addition of a
_____poly A tail_________________.
15) The model of protein evolution through the combination of different exons is called the
______exon shuffle_______________ model.
16) In eukaryotes, transcription and RNA processing takes place in the

____nucleus____________ whereas translation takes place in the
____cytoplasm____________.
17) Below are two amino acids, alanine and glycine. Draw the dipeptide to show the peptide
bond that would be formed in translation.
18)
19) Electron microscopy of heteroduplex formation between mRNA and its DNA coding
strand is shown below.
a. Which strand is mRNA?
b. How many introns are present?
20) What factors should one consider in expressing eukaryotic genes in prokaryotic cells?
21) Many eukaryotic genes are _______housekeeping______________ genes that encode

essential metabolic enzymes or cellular components and are expressed constitutively at
relatively low levels in all cells.
22) A regulatory base sequence in eukaryotic cells that increases the rate of transcription of
nearby genes regardless of orientation is called a(n) _____enhancer_______________.
23) _______________________ refers to heritable changes in gene expression that are not
due to changes in the DNA sequence itself, but to something "in addition to" the DNA
sequence, usually either chemical modification of the bases, or protein factors bound with
the DNA.
24) In eukaryotes, some enhancers are located many kilobases away from the genes they
regulate. By what means can these remote enhancers stimulate transcription of the genes?
Because of the folding of the chromatid, the enhancer still have a big chance to approach
the genes.
25) Because many eukaryotic genes contain ________intron____________ that are present in
the primary transcribed but removed from the mature mRNA, the cDNA sequence is not
identical with the genomic DNA.
26) The type of gene expression which is constant and independent of on/off regulatory
control is called _______uninducible______________________ gene expression.
27) Please describe the structural differences that exist between eukaryotic and prokaryotic
mRNA molecules! Eukaryotic has 5’cap and poly A tail.
28) What is the biological role of the chromatin remodelling complex in the regulation of
gene expression in eukaryotic cells?
29) Please explain the essence of epigenetic gene regulation! We use modification on DNA
without changing their sequences. Like DNA methylation, miRNA
30) What is the most frequent chemical DNA modification in eukaryotes? What is the
functional consequence of this modification? DNA methylation. It causes genomic
imprinting, X-chromosome inactivation
31) In the human genome there are ~ 23.000 genes. In a human, however, roughly 100 000
different proteins can be detected. What is the explanation for this contradiction?
32) What is the molecular mechanism of RNA interference? When a double-stranded RNA
homologous to the endogenous mRNA coding region is introduced into a cell, the mRNA
is degraded and the gene expression is silenced
33) Describe the major structural differences exist between prokaryotic and eukaryotic genes?
34) What are the cis-regulatory sequences that are involved in the regulation of eukaryotic
genes? promotor, enhancers. They are non-coding proteins
35) What are the trans-regulatory factors that are involved in the regulation of eukaryotic
genes?
36) Why is it possible, that silencers or enhancers could be located very far from the actual
genes that are regulated by these sequences?
37) Please describe how the pre-mRNA is converted into mRNA in eukaryotes! By RNA
splicing. After splicing the introns were removed.
38) Why transcription and RNA processing are coupled processes? What is the advantage of
coupling these processes? To greatly increase the speed and specificity of RNA
processing. Otherwise many mistake will happen if the reaction is not coupled
39) Please characterize the general structure and function of spliceosomes! It is composed of
five small nuclear RNAs (snRNA), U1 U2 U4 U5 U6 and a range of associated protein
factors. When these small RNAs are combined with the protein factors, they make an
RNA-protein complex called snRNP. They splice the introns away from the pre mRNA.
40) Compare eukaryotic and prokaryotic ribosomes with respect to

a. sedimentation coefficient. The eukaryotic sediment faster than prokaryotic
b. subunit structure
c. antibiotic resistance
41) What do you mean by a charged tRNA? What is the name of the enzyme, responsible for
its synthesis? aminoacyl tRNA synthetase. It means the tRNA to which its cognated
amino acid is chemically bond. E
42) Describe the most important events of translation initiation in prokaryotes. The two
ribosomes (50s and 30s) attached to the mRNA. The charged tRNA. GTP as the energy
source.
43) Describe the most important events of translation initiation in eukaryotes.
44) Name the 3 most important binding sites of the ribosome. What are their functions? E P A
site. E site is the leaving of tRNA. P site is the poly peptide formed. A site is the
attachment of the newly arrived tRNA.
45) What are the most important steps of the elongation during translation? (1) positioning
the correct aminoacyl-tRNA in the A site of the ribosome, (2) forming the peptide bond
and (3) shifting the mRNA by one codon relative to the ribosome
46) Where does the ribosome begin its “scanning” work, and what is the ribosome searching
for?
47) Compare eukaryotic and prokaryotic mRNAs with respect to the number of cistrons in it.
48) Is it possible to translate an mRNA in a bacterial cell if it lacks the Shine-Dalgarno

sequence? Explain.
49) What will recognize the STOP codons in translation? What is its chemical nature? In
prokayrotics the RF1 2 3 in eukaryotic the eRF1 2 both GTP related
50) Describe an experiment, which led to the recognition of the meaning of a codon.
51) What are the most important characteristics of the genetic code? To transcript and
translate the DNA and RNA into proteins.
52) Give an example of a genetic system that does not use the standard genetic code: prion
protein
53) How could you explain some side-effects of translation inhibitor antibacterial antibiotics
during treatment?
54) What is coupling of transcription and translation? Where does it take place?
55) What is the significance of wobble in codon-anticodon base pairing? our bodies have a
limited amount of tRNAs and wobble allows for broad specificity, wobble base pairs have
been shown to facilitate many biological functions
56) A nucleotide is inserted into the coding region of an mRNA. What are the consequences
of this event?
57) .……aminoacyl………………….. ……tRNA…… …synthatases…………binds the

amino acid to its corresponding (cognate) tRNA.
58) ……wobble…………………….is the name of the special feature of codon-anticodon

base pairing that accounts for the observation that certain bases at the 5’ end of an
anticodon can pair with any of two or more bases at the 3’ end of the codon therefore the
cells contain less than 61 different tRNA molecules.
59) What are transposable elements? Are they able to leave the cell? Alike the pseudogenes.
They are a DNA sequence, which can change its position within a genome, sometimes
creating or reversing mutations and altering the cell's genetic identity and genome size.
60) Describe the mechanism of transposition for retrotransposons. Mention at least one
example of it. Transposition are catalyzed by several transposase. Non-specifically bind
to any target site in DNA, staggered cut at the target site producing sticky ends, cuts out
the DNA transposon and ligates it into the target site. e.g. helitron. Retroransposons will
first transcript itself into RNA and reverse transcribe to DNA, and insert into any
fragment of DNA
61) There are two basic mechanisms for DNA mediated transposition. One of them does not
increase the copy number/ cell, the other one does. Name these mechanisms.
62) LINE-1 sequences constitute about 1/6 of the human genome. Describe at least 3 features
of this genetic element.
63) Alu sequences constitute about 10% of the human genome. Describe 3 important features
of this genetic element.
64) What is the consequence of the recombination between two direct repeats and two
inverted repeats, respectively?
65) What kind of DNA rearrangements can be caused by the recombination between different
copies of a transposon?
66) You see 4 different crossover events on the picture above. Name these events and
describe their outcomes.
67) Transposable elements can cause mutation by two basic mechanisms. Name these
mechanisms.
1) Which phase of the cell cycle is optimal for studying chromosomes? Metaphase
2) What is the role of colchicine in chromosome investigations? It is a mitosis- inhibition

drug. So that we can investigate the chromosome.
3) What is the role of phytohemagglutinin in chromosome investigations? Induce mitosis
4) Define the term: haploid. Only single set of chromosome.
5) Define the term: diploid. Two sets of chromosome.
6) Which human cells are haploid? Gametes.
7) Which human cells are diploid? Nearly every cell in human body.
8) What is the chromosome number of a human gamete? 23
9) How many chromosomes are in a human zygote? 46
10) Define the term: aneuploid. Aneuploidy is the presence of an abnormal number of
chromosomes in a cell
11) What does it mean: triploid? There cops of each chromosome
12) What is the name of the chromosome complement which is described in the karyotype as
92,XXYY? Tetraploid
13) What is ideogram? A stylized karyogram. The chromosomes are lined up along their
centrosomes dividing short arm and long arm.
14) What is karyogram? A diagram or photograph of the chromosomes of a cell, arranged in

homologous pairs and in a numbered sequence
15) What is a karyotype? the chromosomes of a cell, usually displayed as a systematized

arrangement of chromosome pairs in descending order of size
16) Describe the female and the male human karyotypes with the international symbols. 46,
XX. 46, XY
17) Is a person viable with the karyotype 69,XXX? No they died within few days.
18) Define the term monosomy. What does it mean? A chromosome having no homologue,
especially an unpaired X chromosome.
19) Name a monosomy syndrome in humans. Turner syndrome
20) Define the term disomy. Does it mean a chromosome aberration in humans or not?
21) Which is the best known human trisomy syndrome? Downs syndrome, PATAU
syndrome, Edwards syndrome
22) 47,XX,+21. This karyotype refers to ………downs syndrome…………

23) What is the difference between trisomy and triploidy?
24) Describe the karyotype of a Down syndromic female baby. 47,XX,+21
25) Describe the karyotype of a Down syndromic male baby.
26) Which chromosomal abnormality is the basis of Patau syndrome? 13 chromosome

trisomy
27) Which numerical chromosome abnormality is the cause of Edwards syndrome? 18
28) Name three important symptoms (signs) of Down syndrome. Flat face, growth failure,
short and broad hands.
29) What are the life expectations of 47,XY,+13 and 47,XX,+18 babies. 13 ten years. 18 first
year
30) Describe the standard karyotype of a healthy human female. 46,XX
31) Describe the standard karyotype of a healthy human male.
32) What is indicated by the 47,XXX karyotype? Is this person healthy or not? Healthy
33) How many Barr bodies can be seen in the cell nuclei of a 47,XXX person? 2
34) Are there any Barr bodies in the cell nuclei of Klinefelter syndromic patients? Yes one.
35) “Dosage compensation”. What does it mean in genetics? Why is it necessary? To

compensate that male has only one X sex chromosome. X inactivation
36) Do all the cell nuclei of a healthy female express exactly the same genetic information?
Explain. No
37) On which chromosome is the primary sex determinant gene located? Y sry
38) Is it possible that someone shows female phenotype with 46,XY chromosomes?
If yes, how? If not, why not? Yes, by mutation of SRY, the indifferent gonads fail to
differentiate into testes in an XY (genetically male) fetus.
39) Is it possible for someone to have male phenotype with 46,XX chromosome set?
If yes, how? If not, why not? Yes, is caused by unequal crossing over between X and Y
chromosomes during meiosis in the father, and results in the X chromosome containing
the SRY gene
40) Give three important and characteristic symptoms of the Turner syndrome, including the
chromosome complement of Turner syndromic patients. 45, X, short stature, broad chest.
41) Give three examples of structural chromosome aberrations. Deletions, duplications,

translocation.
42) Give three examples of diseases based on structural chromosome aberrations.
43) In which disease can you see Philadelphia chromosome and what is its role in the
development of that disease? chronic myelogenous leukemia, the 9 and 22 chromosome
exchanges their long arm.
44) Robertsonian translocation. Give an example of that aberration. An entire chromosome

has attached to another at the centromere - in humans these only occur with chromosomes
13, 14, 15, 21, and 22
45) Why is it important to make a precise chromosomal diagnosis of Down syndrome in a

newborn infant?
46) Is the probability of recurrence of Down syndrome the same in each family in which that
chromosomal abnormality occurred?
47) A child was born with symptoms of Down syndrome. The attached karyogram belongs to
the mother of this child. What are her chances of having another child suffering from
Down syndrome? Explain.
48) What is meant by "dosage compensation"?
49) Chromosomes are often classified according to the relative position of the centromere.
Name and describe the different classes of human chromosomes.
metacentric, submetacentric, acrocentric, telocentric.
50) Below a karyogram is shown. Give the karyotype of the person and the symptoms
associated to this karyotype. What is the theoretical probability that this person has a
child with Klinefelter syndrome? No symptoms, this person is healthy. Sometimes
learning problems. 1/4
51) What does the Lyon hypothesis say about the inactivation of sex chromosomes?
認為有些異型合子的雌性老鼠之所以會有斑駁的毛色，是因為其中一個X染色體失
去了活性，且毛色基因就位在此染色體上
52) Describe the genetic background of Prader-Willi (chromosome number 15 from father is
imprinted, or both of the chromosome 15 comes from mother）syndrome and Angelman
syndrome. (chromosome 15 from mother part long arm is imprinted, or both of the
chromosome 15 comes from father)
53) The frequency of 47,XXY karyotype was found 4/7,500 in spontaneous abortions and
44/85,000 live births. Does that aneuploidy influence viability? Explain.
54) Why are humans so tolerant of aberrant numbers of sex chromosomes? There are many
repetitive genes in human body. Y染色體基因很少。X是因為inactivation
55) List at least four types of abnormalities in chromosome structure:

A. .............................................
B. ..............................................
C. ..............................................
D. ..............................................
56) In genetics clinic you are counseling pregnant women who inquire about their risk of
having a Down-syndrome fetus. What are their risk and why?
A. a 23-year-old mother of a previous trisomy 21 child.
B. a 41-year old mother of a previous trisomy 21 child.
C. a carrier of a 14;21Robertsonian translocation.
D. a woman whose husband is a carrier of 14;21 Robertsonian translocation.
57) How can a person with a 46,XX karyotype differentiate as a phenotypic male? Give a
possible explanation! It is caused by unequal crossing over between X and Y in meiosis 1
in the father.
58) Carefully study the attached karyogram. Describe the karyotype, name the syndrome and
the main symptoms of it.
59) In certain cell types, the ___barr body_____ in females can be observed microscopically
as a densely staining heterochromatic body in the nucleus of interphase cells.
60) An arrangement of metaphase chromosomes according to their length and centromere

placement is called a ___karyotype____.
61) The fusion of the centromere region of two nonhomologous acrocentric chromosomes is
called a ___Robertsonian translocation ____.
62) The inversion, in which the centromere is not included in the inverted region, is known as
a ____parocentric_________ inversion.
63) When the inversion does include the centromere it is called a ___pericentric_ inversion.
64) One of the consequences of X-chromosome inactivation is that a normal female is a

_______mosaic_________ for X-linked genes.
65) What is the Philadelphia chromosome?
66) Some XY individuals phenotypically look like females and some XX individuals like
males. What chromosomal abnormality could account for this?
67) On the figure below you see the karyogram of a person. Describe the karyotype and the
health status associated to this karyotype.
68) On the figure below you see the karyogram of a person. Describe the karyotype and the
health status associated to this karyotype.
69) See the karyogram below. Give the karyotype. Name the syndrome and describe the
characteristic phenotypes.
70) See the following karyogram. Give the karyotype, name the syndrome and describe its
main symptoms.
71) What is the role of phytohemagglutinin (PHA) and colchicine in making of chromosome
spreads?
1) Describe fragile-X syndrome? What is the genetic basis of the syndrome?
Fragile-X is a genetic syndrome that is the most widespread single-gene cause
of autism and inherited cause of mental retardation among boys.
Fragile X syndrome is associated with the expansion of the CGG trinucleotide repeat.
2) Assuming equal number of boys and girls in the population, what is the probability
that a couple will have seven girls? If they already have six girls, what is the
probability that the seventh child will be male? The probability of having a girl or a
boy is equal (1/2) since the events are mutually exclusive.
Therefore the probability of having 7 girls is – ( ½ )^7 = 1/128
The probability of having a boy is independent of the sex of previous births, therefore the
chance is ½
3) A phenotypically normal couple has a normal daughter and a son with hemophilia.
What are the genotypes of the parents? What is the probability that the daughter
is heterozygous? Remember: hemophilia is a recessive X-linked disease.
Healthy male doesn’t have the recessive allele
Father: XAY
Since their son is affected, and he inherits the Y from his father, the mother must be
heterozygote
Mother: XAXa
Son: XaY
Daughter: XAX- - 50% chance that the child is heterozygote (the healthy allele is from the
father, yet she may inherit any of the 2 alleles the mother carries)
4) Consider a fully heterozygous flowering plant with normal blue flowers and round
seeds. This plant when crossed with one that has red flowers and oval seeds,
result in the following progeny:
a) 91 blue, round
b) 94 red, round
c) 93 blue, oval
d) 92 red, oval
Write up the cross! What is the recombination frequency? Are the genes linked?
Assumption: B – blue color, b – red color, R – round shape, r – oval shape.
Cross: BbRr X bbrr (blue and round X red and oval)
a) BbRr
b) bbRr
c) Bbrr
d) bbrr
Since there is approximately an equal amount of each phenotype, the genes are not
linked – there is an independent segregation of alleles, 50% frequency of recombinant
gamets.
5) The inheritance of hemophilia in a family is shown in the pedigree. What is the

probability that III/5 is carrier? What is the probability that her 5th child will be
affected?
Ch7 Transmission genetics 1/34

Remember: hemophilia is a recessive X-linked disease.
I1 – XAXa, I2 – XAY
II3 – XAXa, II4 – XAY
III5 has a 50% chance to be a carrier since her mother is carrier.
The probablety of an affected child is ½ * ¼ = 1/8 (1/2 chance that the mother is a carrier,
¼ that their child will be affected – with the help of a punnett square)
6) In the pedigree shown here, the shaded symbols represent persons affected with
hemophilia.
If the woman identified as II/2 has two more children, what is the probability that
neither will be affected?
Genotype of II2 - XAXa

Accroding to punnett square the probabelty that a child won’t be affected is 3/4, the
probability that both children won’t be affected is 3/4* 3/4= 9/16
7) Two normally pigmented persons of the Caucasian race have a child with
albinism. What is the probability that the parents have another child with albinism?
What is the probability that they have children that are carrier of the albino allele?
Remember: Albinism is an autosomal recessive allele.
The probability of having a child with albinism is ¼.
The probability that a child will be a carrier is ½.
8) In the pedigree shown here, the shaded symbols represent persons affected with
hemophilia.
What is the probability, that the first child of the mating II-4 x II-5 will be affected?
There is a chance of 50% that II-4 is a carrier, according to punnett saure of the desired
cross there is a chance of 25% that a child will be affected, overall (1/2*1/4) a chance of
1/8 that their first child will be affected

9) Several testcrosses have revealed the rate of recombination for the following
genes:
k-m 0.30
k-l 0.8
l-m 0.50
What is the order of the three genes?
The frequency of crossing over is proportional to the distance of the genes on a given
chromosome.
0.3 0.5
K L
M
0.8
10) Explain the term: recessive epistasis. Give a human example.

Epistasis is when one gene masks on the expression of another gene; recessive
epistasis is when the recessive homozygosity masks the expression (phenotype) of
another gene whether it is dominant or recessive.
Example: the gene that causes albinism will mask the gene that is responsible for the
color of the person's hair.
11) Explain the meaning of the term: linkage group.

Linkage group is a group of genes that are located close to each other on the same
chromosome and tend to be transmitted together.
12) In a Mendelian cross the 9:7 ratio of progenies in F2 is characteristic of

complementary genes
13) Disregarding crossing over, which increases the degree of genetic variability,
estimate the probability that all your chromosomes have come to you from your
father's mother and from your mother's mother. Provided this was the case, would
you be male or female?
The chance that I’ve received my mother’s mother chromosomes are ½ and the chance
I’ve received my father’s mother chromosomes is also ½ , over all a chance of ¼ .
In this case I would be a female.
(Explanation: let’s assume my father’s mother had the chromosomes XAXA, and my
mother’s mother had XBXB, my mother’s father had XCY.
This would mean that my father has XAY and my mother has XBXC, we are interested in a
case where a child has XA (father’s mother) and XB (mother’s mother), there is a chance
of ½ for each, and it will be a female.. draw it..)
14) In the human pedigree shown here, the female indicated by the solid circle has a
form of deafness determined by an autosomal recessive allele. What is the
probability that her phenotypically normal brother (indicated by the open square)
is heterozygous for the gene?

With the help of a punnett square we can see that the probability is 2/3
A a
Since it is given that her brother is not deaf we
A AA Aa
will examine only 3 cases in which the A allele is
A Aa aa
present.
Only two of these cases are heterozygot -> 2/3
15) What gametes and at what ratio are produced by an individual of genotype AaBb
if the two loci are (a) on different chromosomes or (b) if A and B are on the same
chromosome and their distance is 10 centimorgan?
If the genes are on different chromosomes, the ratio of the parental gametes will be equal
to the recombinant gametes (50%-50% parental-recombinant).
Gametes and their ratios: AB (25%) parental , Ab (25%) recombinant , aB (25%)
recombinant, ab (25%) parental.
If A and B are on the same chromosome and their distance is 10 cM, it means that we
will have 10% recombinants (because the frequency of crossing over is proportional to
the distance of the genes on the chromosome), and 90% parental.
Gametes and their ratios: AB (45%) parental, Ab (5%) recombinant, aB (5%)
recombinant, ab (45%) parental.
16) Huntington disease is a rare degenerative human disease determined by a

dominant allele, H. The disorder is usually manifested after the age of forty. A
young woman learns that her father has developed the disease. What is the
probability that a child of the young woman carries the H allele?
The father has at least one dominant allele (H-), we can assume that his wife is healthy
(hh), their daughter can be heterozygote to the disease (Hh) or healthy (hh), that means
that she has ½ probability of having the disease. Assuming she will marry a healthy male
their child has ½ probability of being a heterozygote. Over all ½ * ½ = ¼
17) Knowledge of the AB0 genotypes of a certain couple leads us to say that if they
have many children, the ratios of the children's blood types will be expected to
approximate 25% type B, 25% type AB, and 50% type A. Give the genotypes of
the couple.
IA IO
IA IA IA IA IO
IB IA IB IB IO
18) Instead of the expected 9:3:3:1 ratios in an F2 generation from true-breeding

parents one sees a 9:7 ratio. How can you explain? What does this suggest about
the metabolic requirements for phenotype expression in this case?
This ration is a variation of the 9:[3:3:1] ratio. We can observe a complementary gene
activity, which means that a certain phenotype can be seen only if two active alleles are
present A-B-, otherwise the genes won’t be active.
The genotype -aa or –bb blocks the metabolic pathway:
‫ גם אם רק איזור‬,‫ הסימן לא חייב להופיע יחד‬,‫ נוכחים‬bb ‫ או‬aa ‫)הסימן האדום מתאר מצב בו הגנוטיפ‬
(‫ עדין הפיגמנט הכחול לא יתקבל‬Bbaa-‫אחד נחסם כמו ב‬

19) If two parents who are both blood type A and have normal vision produce a son
who is color blind and is type 0, what is the probability that their next child will be
a female who has normal vision and is type 0?
If both parents have blood type A and they have a child who is O blood type, we can
conclude that the parents are both heterozygous for blood type IAIO. The chance that
they will have a child with O blood type is 1/4.
Color blindness is a recessive X-linked disease.
If both parents have a normal vision, it means that the father has a healthy X
chromosome and that the mother is a carrier of the disease. The chance that the next
child will be a female AND have a normal vision:
XA Xa The chance that the next child will be a female AND have
A A A A a normal vision is 1/2.
X X X X X
In general, the chance that the next child will be a female that
Y XA Y Xa Y have normal vision AND blood type O is 1/4 x 1/2 = 1/8.
20) On the pedigree II/2 is affected by a recessive trait. What is the genotype of II/2?
What is the probability that II/3 is a heterozygous “carrier” of the “a” allele?
A person is affected by a recessive trait only when his genotype is aa (II-2) which
means that the parent’s genotype must be heterozygoe, both are Aa.
We can see that II-3 is healthy so he must have an A allele, the probability of him
being a heterozygote is 2/3.
A a
A AA Aa
a Aa aa
21) The pedigree below is for a rare autosomal recessive trait with complete
penetrance. What is the probability that at least one of IV-1, IV-2 and IV-4 is a
carrier?

Penetrance is the proportion of individuals in the population that carry a specific variation
of a certain gene and actually exhibit the associated trait of that genotype.
When we have a recessive trait with complete penetrance, it means that every individual
who is homozygous to that trait will exhibit the phenotype associated with the genotype.
In this case, we know that IV/3 is affected, which means she has a homozygous
recessive genotype, and because both parents are NOT AFFECTED they are carriers of
this trait.
The chance that at least one of IV/1, IV/2 and IV/4 is a carrier is 2/9
The formula for picking an individual when order has no importance: nCr x p^r x q^(n-r),
where n is the total number of individuals within the group, r is the number of individuals
we want to pick, p is the probability of picking a carrier ("success") and q is the probability
of picking a non carrier ("failure"). In this case: n=3, r=1, p=2/3, q=1/3 (we exclude the aa
possibility because we already know that non of IV/1, IV/2 and IV/4 are sick).
22) In four-child families, what proportion of them has at least one boy?
The same formula as in the previous question: nCr x p^r x q^(n-r).
We want to pick AT LEAST one child to be a boy, that means that we can pick either 1, 2,
3, or 4 out of four children. The easiest way to calculate the probability of picking at least
one is using the complement event: what is the probability that all children will be girls
(which means we pick 0 boys out of four).
The parameters: n=4, r=0, p=q=1/2 (the chance of having a boy or a girl is 1/2).
The chance that all 4 children will be girls: 1/16
The chance that at least one child will be a boy: 1-1/16 = 15/16.
23) The allele H is required for the completion of A and B antigens. In its absence, the
allele h cannot direct the formation of A and B antigens. The h allele, when
homozygous is thus epistatic to the AB0 locus and can cause a person to be
seemingly blood type 0 regardless of the presence of the A and B alleles. Give
the blood types expected among the offspring in the following mating, as well as
the ratio in which they occur:
IAIBHh x IAIBHh
IAH IBH IAh IB h

IAH IAIAHH IAIBHH IAIAHh IAIBHh
IBH IAIBHH IBIBHH IAIBHh IBIBHh
IAh IAIAHh IAIBHh IAIAhh IAIBhh
IBh IAIBHh IBIBHh IAIBhh IBIBhh
All blood types are present – AB,O,A,B the ratios are 6:4:3:3
24) Define the term “epistasis”.
Epistasis is when one gene masks on the expression of another gene; recessive
epistasis is when
25) Mice with a single X chromosome and no Y chromosome (an X0 chromosome

constitution) are fertile females. If at least one X chromosome is required for
viability, what sex ratio is expected among surviving progeny from the mating of
an X0 female and an XY male?
2 female mice
1 male mouse
26) Describe the term penetrance.

% of people with the predisposing genotype who are actually affected at least to some
degree.
27) Define the term “pleiotropy”. Give an example.

A single gene controlling or influencing multiple (and possibly unrelated) phenotypic
traits.
Example:The human disease PKU (phenylketonuria). This disease can cause mental
retardation and reduced hair and skin pigmentation, and can be caused by any of a large
number of mutations in a single gene that codes for an enzyme (phenylalanine
hydroxylase) that converts the amino acid phenylalanine to tyrosine, another amino acid.
28) Analyze the attached pedigree and indicate the mode of inheritance of the trait
shown. List at least three traits with medical significance which follows the same
pattern.
 no pedigree 
29) In Drosophila, the eye-color mutation scarlet (st) and the bristle mutation
spineless (ss) are located in chromosome 3 at a distance of 14 map units. What
phenotypes, and in what proportions, would you expect in the progeny from the
mating of st+ ss+ / st ss females and st ss / st ss males?
st+ and ss+ symbolizes the strong and dominant allele.
st+ ss+ st ss
X
st ss st ss
for simplification female phenotype is AaBb and the male’s is aabb.
AB aB Ab ab
ab AaBb aaBb Aabb aabb
The marked gametes are recombinant. The distance in map units is proportional to the rate
of recombination. Each recombinant product has 7% frequency (over all 2 recombinant
gametes – 14%).
Observed phenotypes: Normal eye color and normal spine?
Mutation scarlet and normal spine
Normal eye color and bristle mutation spineless
Mutation scarlet and mutation spineless
30) The next pedigree shows inheritance of phenylketonuria in a certain family. If
persons III/1 and III/2 mate, what is the probability that their offspring will be
affected? Assume that II/1 and II/5 are homozygous for the normal allele.
Remember: PKU is autosomal recessive

Since II-3 is affected and her parents are healthy, both of them are heterozygotes (Aa).
The chance that II-2 and II-4 are heterozygotes are 2/3 each.
We know that II-1 and II-5 are AA.

In this case (considering II-2 and II-4 are hetero) the chance that III-1 and III-2 are
heterozygote is ½ .
In case both III-1 and III-2 are carriers, the chance that their child will be affected is ¼
Over all: 2/3 * 2/3 * ½ * ½ * ¼ = 1/36
31) Assuming independent assortment, how many different gametes can be formed
by an organism that is heterozygous for n genes?
In independent assortment, an organism can form two different gametes for each gene. If
the organism has n genes, it can form 2n gametes.
32) In the accompanying pedigree the shaded symbols represent persons affected
with hemophilia, a blood-clotting disorder.
What is the probability that from the marriage of II/4 and II/5 the first child will be
healthy?
Remember: hemophilia is a recessive X-linked disease.

The chance that II-4 is a carrier is ½ , in case she is there is a chance of ¾ that their child
will be healthy, overall: ½ * ¾ = 3/8
33) Certain recessive genes cause profound hereditary deafness, and individuals
homozygous for such genes are occasionally found in high frequencies among
extended families in small isolated communities. The mutations originate in
individuals several generations in the past, and become homozygous through
marriages among relatives. A deaf man and a deaf woman from two different
communities, each having deaf parents, had three children, all of whom had
normal hearing. How would you explain this?
This can be explained by Complementary gene activity. Let’s say that aa causes
deafness, yet in the special situation of bb, the hearing won’t be impaired. The parents
must have been aaBb and aaBb and the children are aabb.
Recessive epistasis??
34) The following pedigree shows the inheritance of hypophosphatemic rickets in a

family. How is the trait inherited?

The disease is X-linked dominant
35) In the fruit fly the allele for purple eye color p is recessive to its allele for red p+.
The allele for vestigial wings vg is recessive to the wild type allele for normal wing
vg+. The two genes are autosomally linked. Females from a purple stock are
crossed to males from a vestigial stock. The F1 flies are all wild (red eyes normal
wings). F1 females are testcrossed with the following results:
Purple, normal wing 210

Wild 40
Red, Vestigial 215
Purple, vestigial 35
Write up the testcross. Calculate the frequency of recombination.

We know that the females have purple eyes, yet we have no information about their
wings: __pp, the males have vestigial wings yet we have no information about their eyes:
vgvg__. The only way the offspring in F1 are wild types is if the females are vg+vg+pp and
the males are vgvgp+p+. The offspring’s genotype is: vg+vgp+p.
Test cross: vg+vgp+p X vgvgpp
vg+p+ vg+p vgp+ vgp
+ + + +
vgp vg vgp p vg vgpp vgvgp p vgvgpp
Recombinant gametes are the ones that have the lowest number of offspring, according to
the information we got, wild type has 40 offspring and purple, vestigial have 35 overall 75
offspring out off 500: 75/500*100 = 15% recombinant (7.5% for each type of recombinant
gamete).
36) Assuming equal number of boys and girls in the population, what is the probability
that a couple will have seven girls? If they already have six girls, what is the
probability that the seventh child will be male?
See question number 2
37) At what stage of meiosis does segregation of alleles take place? Explain!
In meiosis, segregation of alleles takes place during anaphase I because during this
phase, the homologous chromosomes separate, so that each gamete is equally likely to
contain either member of the pair of alleles.
38) Define the term expressivity.

It is the severity of of expression of the phenotype (disease) among individuals with the
same disease-causing genotype.

39) The shape of radish may be long (SHSH), round (SKSK), and oval (SHSK). The
phenotype of the parental generation was oval and long. What is the phenotypic
ratio in the F2 generation resulting from the cross of the individuals in F1?
P: SHSK X SHSH
F1 - 1:1 SHSH , SHSK
SH SK
H H H
S S S SHSK
H H H
S S S SHSK
F2: ?‫צריך לפרט על כל שלושת המקרים‬
We have 3 possible crosses, 1st cross is identical to the parental cross – 50% long, 50%
oval.
2nd cross: SHSH X SHSH, 100% long
3rd cross: SHSK X SHSK, 25% long, 50% oval, 25% round.
SH SK
SH SHSH SHSK
K H K
S S S SKSK
40) The allele pair CGCG determine the dark green coloration of the cotyledon of field
bean. The heterozygous CGCY genotype causes a light green coloration; the CYCY
genotype causes a yellow color, and is lethal for the plant because of the absence
of chlorophylls. The phenotype of the parental generation was dark green and
light green. What is the phenotypic ratio in the F2 generation resulting from the
cross of the individuals in F1?
P: CGCG X CGCY
F1:
CG CY
G G G
C C C CGCY
G G G
C C C CGCY
F2:
We have 3 possible crosses, 1st cross is identical to the parental cross – 50% dark green,
50% light green.
2nd cross: CGCG X CGCG, 100% dark green
3rd cross: CGCY X CGCY, 25% dark green, 50% light green, 25% yellow – not viable.
CG CY
G G G
C C C CGCY
Y G Y
C C C CYCY
41) A yellow pigmented line at the top of the hair causes the specific fur colour
„agouti” in rodents. The following phenotypes are caused by multiplex series of
alleles in rabbits: genotypes EDED and EDe cause black fur colour, EDE causes
black fur with agouti patches, EE and Ee are agouties, and ee is reddish yellow.
What is the expected phenotypic and genotypic ratio in the F1 and F2 generation
resulting from the cross EDED Ee?
F1:
ED ED
D
E E E EDE
D
e E e EDe
Genotypic ratio: 1:1, phenotypic ratio: 50% black fur with agouti patches, 50% black fur
F2:
3 possible crosses.

1st cross: EDE X EDE: 25% black fur (EDED), 50% black fur with agouti patches (EDE), 25%
agouti (EE)
2nd cross EDe X EDe: 75% black fur (25 % EDED/ 50 % EDe), 25% radish yellow (ee)
3rd cross EDE X EDe: 50% black fur (25% EDED / 25% EDe), 25% black fur with agouti patches
(EDE), 25% agouti (Ee).
42) A yellow pigmented line at the top of the hair causes the specific fur colour
„agouti” in rodents. The following phenotypes are caused by multiplex series of
alleles in rabbits: genotypes EDED and EDe cause black fur colour, EDE causes
black fur with agouti patches, EE and Ee are agouties, and ee is reddish yellow.
What is the expected phenotypic and genotypic ratio in the F1 and F2 generation
resulting from the cross EDe ee ?
F1:
ED e
E EDe ee
E EDe ee
Genotypic ratio: 1:1, phenotypic ratio: 50% black fur with agouti patches, 50% radish
yellow
F2:
3 possible crosses.
1st cross: EDe X EDe: 75% black fur (25 % EDED/ 50 % EDe), 25% radish yellow (ee)
2nd cross ee X ee: 100% radish yellow (ee)
3rd cross EDeX ee: 50% black fur (EDe), 50% radish yellow (ee).
43) The normal nails and legs of pigs are determined by a recessive (m) allele, the
vestigial form by a dominant (M) allele. The white color of the hair is caused by a
dominant (B) allele, the black by a recessive (b) allele. A white female with
vestigial legs was crossed with a black male with normal legs. The resulting
phenotypic ratio among the offspring was: 26 white with vestigial legs. What was
the possible genotype of the female?
The mother has to be BBMM and the father is bbmm and
F1: has to be BbMm when crossed with a recessive father.
dominant (B) allele, the black by a recessive (b) allele. A white female with
vestigial legs was crossed with a black male with normal legs. The resulting
phenotypic ratio among the offspring was: 8 white with vestigial legs and 1 white
with normal legs. What was the genotype of the female?
BBMm
dominant (B) allele, the black by a recessive (b) allele. A white female and male
with vestigial legs were crossed. The resulting phenotypic ratio among the
offspring was 8 white with normal legs, 7 black with vestigial legs, 25 white with
vestigial legs, 3 black with normal legs.
Test cross was made with each of the black offspring with vestigial legs. What is
the expected phenotypic ratio in the resulting generation?
2 test crosses: bbMM X bbmm = 100% black with vestigial legs,

bbMm X bbmm = 50% black with vestigial legs, 50% black with normal legs.
Overall: 3:1
dominant (B) allele, the black by a recessive (b) allele. A white female and male
with vestigial legs were crossed. The resulting phenotypic ratio among the
offspring was 8 white with normal legs, 7 black with vestigial legs, 25 white with
vestigial legs, 3 black with normal legs.
What is the expected phenotypic ratio in the resulting generation, if we performed
test cross of white mother with vestigial legs?
Possible genotypes: BBMM, BbMM, BBMm, BbMm. Each possible genotype is crossed
with bbmm:
1) BBMM X bbmm = BbMm – 100% white with vestigial legs
2) BbMM X bbmm = 50% BbMm - white with vestigial legs , 50% bbMm -black with
vestigial legs
3) BBMm X bbmm =50% BbMm - white with vestigial legs , 50% Bbmm - white with
normal legs
4) BbMm X bbmm = 25% of each: white, vestigial; white, normal; black, vestigial; black,
normal.
Overall: 9:3:3:1 – white,vestigial : white normal : black vestigial : black normal
47) The dominant K allele determines the curvy, the homozygous recessive allele pair
(kk) the normal tail of mice. Homozygous phenotype AA causes grey, agouti hair,
the heterozygous ASA is yellow, and the homozygous ASAS is lethal. Performing a
cross between yellow mice with heterozygous curvy tails, what phenotypic ratios
are expected among the offspring?
P: ASAKk X ASAKk
F1:
ASK ASk AK Ak
S
A K ASASKK ASASKk ASAKK ASAKk
S
A k ASASKk ASASkk ASAKk ASAkk
AK ASAKK ASAKk AAKK AAKk
Ak ASAKk ASAkk AAKk AAkk
AAK- : 3 agouti hair, curvy tail

AAkk :1 agouti hair, normal tail
ASAS-- : lethal (4)
ASAK- : 6 yellow, curvy tail
ASAkk :2 yellow, normal tail
the heterozygous ASA is yellow, the homozygous ASAS is lethal.
Performing a cross between yellow mice with heterozygous curvy tails, at what
ratio will the offspring with ASAKk genotype be produced?
According to the above punnett square: 4/12 ->1/3
the heterozygous ASA is yellow, the homozygous ASAS is lethal. Performing a

cross between yellow mice with heterozygous curvy tails, what phenotypes and
genotypes of the progenies will survive and at what ratio, if we make the random
mating between yellow offspring from F1?
As we can see in the table from question 2 there are 3 kinds of yellow offspring: ASAKK,
ASAKk, ASAkk
6 kinds of crosses: ASAKK X ASAKK, ASAKk X ASAKk, ASAkk X ASAkk, ASAKk X
ASAKK, ASAKk X ASAkk, ASAKK X ASAkk
??‫לפרט על כל ששת הקרוסים‬
50) According to a gardener’s observations the leaves of some bean plants are fuzzy
and of others are bald. He crossed some of the plants and examined the
progenies.
cross parents progenies
fuzzy Bald
1 fuzzy × bald 82 79
2 fuzzy × fuzzy 102 0
3 bald × bald 0 156
4 fuzzy × bald 92 0
5 fuzzy × fuzzy 153 51

a) What kind of inheritance is it?
b) What are the genotypes of the parents in each crosses?
Fuzzy is dominant (A) over bald (a)

1. Aa X aa
2. AA X AA(Aa X AA)
3. aa X aa
4. AA X aa
5. Aa X Aa
51) Two phenotypes can be observed among the individuals of a bird species:
individuals carrying tuft on their heads (tufted) and individuals that have not got
any tuft (plain). Crossing of the different individuals results in the following
phenotypic ratios:
cross parents progenies
plain tufted
1 plain × plain 105 0
2 plain × tufted 82 78
3 tufted × tufted 31 63
a) What kind of inheritance is it?

b) What are the genotypes of the parents in the different crosses?
Tufted is dominant (T) over plain (t)
1. tt X tt
2. tt X Tt
3. Tt X Tt
52) The silver colouration of the feather of chickens is X-linked (called Z-linked in
chickens; Y = W) and determined by a dominant S allele. The recessive s allele
causes yellow colouration. What were the phenotypic and genotypic ratios in a
cross between a yellow male and a silver female?
ZsW X ZSZ-
Male: ZSW, ZsW(??)
Female: ZSZs, ZsZs(??)
53) Suppose that the ability to roll one’s tongue (dominant) is linked to a rare form of
dwarfism, which is also dominant. If the parents are heterozygous for both alleles,
with the two dominants on one chromosome and the two recessives on the
homologous one, what would be the phenotypic ratio of the offspring? (Assume
no crossing-over.)
Possible gamets: AB, ab
Possible zygotes: AABB, AaBb, aabb
3:1 (roll tongue, dwarfism : can’t roll tongue, normal height)
54) In tomatoes, round fruit shape is dominant over elongate and smooth fruit skin is
dominant over “fuzzy”. Individuals heterozygous for fruit shape and skin type,
when test-crossed, gave the following results:
Smooth, round: 26
Smooth, elongate: 218
Fuzzy, round: 232
Fuzzy, elongate: 24
Are the genes linked? If your answer is yes what alleles are located on the same
chromosome? What is the distance between the two genes in cM?
Since the phenotypes are not evenly distributed, no independent segregation of alleles,
the genes are linked.
P: RrSs X rrss
Parental gametes: rrSs (218), Rrss (232)
Location: Rs/rS
Distance is proportional to the frequency of recombinant gametes: 24+26 = 50
50/(218+232+24+26) = 10% the distance is 10cM.
55) In Drosophila, flies homozygous dominant for grey body and normal wings were
crossed with flies that were homozygous recessive for black body and small
wings. The F1 progeny were test-crossed, with these results:
Grey, normal wings: 410
Grey, small wings: 95
Black, normal wings: 105
Black, small wings: 390
Are the genes linked? If your answer is yes what alleles are located on the same
chromosome? What is the distance between the two genes in cM?
Since the phenotypes are not evenly distributed, no independent segregation of alleles,
the genes are linked.
P: GgWw X ggww

Parental gametes: GgWw (410), ggww(390)
Location: GW/gw
Distance is proportional to the frequency of recombinant gametes: 105+95 = 200
200/(410+95+105+390) = 20% the distance is 20cM.
56) Wild phenotype fruit fly females were crossed with males having purple eyes and
wild type body colour. The phenotypic ratios in the progenies are:
females males
wild eye, black body 15 16
purple eye, black body 17 18
wild eye, wild body 46 48
purple eye, wild body 47 48

a) What were the genotypes of the parents?
b) How these ratios can be explained?
Parents: EeBb X eeBb
The genes are linked, first two are the products of recombinant gametes
57) The alternative forms of a gene are called ___alleles___ of the gene.
58) A genetic cross in which the hybrid organisms are crossed with one of the
parental genotypes is called a __backcrossing___.
59) The various forms of a given gene are called ____allele______.
60) An individual having the same allele of a given gene on homologous

chromosomes is said to be __homozygote_____.
61) In formation of gametes, the paired hereditary determinants

_____segregate_____ in such a way that each gamete is equally likely to contain
either member of the pair.
62) The probability of realization of one or the other of two mutually exclusive events
is the ____sum____ of their separate probabilities.
63) The probability of two independent events, being realized simultaneously, is given
by the ___product___ of their separate probabilities.
64) The ___penetrance____ of a genetic disorder means the proportion of individuals

with the at-risk genotype who actually express the trait.
65) The term __siblings??__ refers to a group of offspring from the same parents.
66) Mating a heterozygous individual with a recessive homozygote is called a

___testcross___.

67) Phenylketonuria (PKU) is a recessive human condition resulting from inability to
convert phenylalanin into tyrosine. Two normal parents have a child with PKU.
a) What is the probability that the parents will have another child that is a carrier
of the recessive allele?
b) What is the probability that out of five children the couple will have three that
are normal and two that have PKU?
Parents: Aa X Aa
The chance of having a child who is a carrier is ¾
The formula for picking an individual when order has no importance: nCr x p^r x q^(n-
r), where n is the total number of individuals within the group, r is the number of
individuals we want to pick, p is the probability of picking a carrier ("success") and q is
the probability of picking a non carrier ("failure"). In this case: n=5, r=3, p= ¾ , q= ¼
5C3 * ¾ ^ 3 * ¼ ^2 = 26%
68) The pedigree in the accompanying illustration shows the inheritance of albinism, a
homozygous recessive condition resulting in a total lack of pigment. Specify the
following genotypes using A and a to indicate dominant and recessive alleles,
respectively. Solid figures represent albino individuals.
a) A-1: Aa
A-2: Aa
b) B-1:Aa
c) B-2: aa
d) C-3: Aa/AA
e) C-4: aa
f) D-5: aa
69) Albinism is a total lack of skin pigment due to a recessive gene. What is the
probability of a couple having an albino child if:
a) She is albino, he is normally pigmented but his father was albino.
b) Both are normally pigmented as are their parents, but both have albino
siblings.
c) He's albino, but she has no albinism in her family history.

a) since he’s father was albino, he must be a carrier – 50% that their child will be
albino
b) Both of their parent are carriers since they have albino children. The chance that
the couple is a carrier is 2/3 each, in case both of them are carriers, there is a ¼
chance that their child will be albino. Overall: 2/3*2/3*1/4 = 1/9
c) she is probably AA , there is no chance their child will be albino
70) Instead of the expected 9:3:3:1 ratios in an F2 generation from true-breeding

parents, one sees a 9:7 ratio. What does this deviation indicate?
This ration is a variation of the 9:[3:3:1] ratio. We can observe a complementary gene
activity, which means that a certain phenotype can be seen only if two active alleles are
present A-B-, otherwise the genes won’t be active.
The genotype -aa or –bb blocks the metabolic pathway
71) In the cross AABB aabb, F2 progeny is produced in a phenotypic ratio of 9:3:4.
What does this deviation from the expected 9:3:3:1 indicate?
This ration is a variation of the 9:3:[3:1] ratio. We can observe a recessive epistasis
activity. The recessive homozygote masks the expression (phenotype) of another gene
whether it is dominant or recessive.
72) In the cross Aa Bb Cc Dd Aa Bb Cc Dd, in which all genes undergo

independent assortment, what proportion of offspring are expected to be
homozygous for dominant alleles of genes A, B and C and heterozygous for gene
D?
1/256
73) The ability to roll the tongue is a dominant trait. In the pedigree below, solid
symbols represent "rollers" and open symbols "non-rollers". Using R and r for
dominant and recessive alleles, respectively, give the likely genotype of:
a) A-1: Rr
b) A-2: Rr
c) B-1: rr
d) B-3: R-
e) B-4: rr
f) C-1: rr
g) C-9: ?????? – ‫איך הוא חולה אם ההורים בריאים‬

74) Use P and p for purple and red and S and s for sweet and non-sweet. If two corn
plants PpSs are crossed, what fraction of the offspring will be
a) Purple : 3/4
b) Non-sweet: 3/16
c) Red and non-sweet: 1/16
d) Red and sweet: 3/16
e) Purple and sweet: 9/16
75) A spontaneous deletion in 15q11 results in Prader-Willi syndrome or Angelman

syndrome. How can the same chromosomal abnormality cause two so different
phenotypes?
Complementary gene action?
76) Separation of the alleles of a single gene into different gametes is called: Meiosis
II?, segregation of alleles?.
77) In cocker spaniels, black color (B) is dominant over red (b), and solid color (S) is
dominant over spotted (s). If the genes are unlinked and the offspring of BBss and
bbSS individuals are mated with each other, what fraction of their offspring will be
black and spotted? Please give your answer here:
Each dog can provide only one type of gamete: Bs and bS therefore there is only one
kind of offspring: BbSs – Black, solid. None of the offspring will be spotted.
78) The blue sclera allele has 90 percent penetrance for producing blue sclera, 60
percent penetrance for fragile bones, and 40 percent penetrance for deafness. If
these probabilities of penetrance are independent, __21.6*_ percent of individuals
with the blue sclera allele will have deafness, blue sclera, and fragile bones.
**since we want all phenotypes, we multiple the chances: 0.9*0.6*0.4 = 0.216
79) In the garden peas used in Mendel’s experiments, the spherical seed character
(SS) is completely dominant over the wrinkled seed character (ss). If the
characters for height were incompletely dominant, such that TT was tall, Tt was
intermediate, and tt was short, what will be the expected result of test crossing the
offspring of a homozygous spherical-seeded, short plant to a wrinkled-seeded, tall
(ssTT) plant?
SStt X ssTT,
Each can provide only one type of gamete: St and sT therefore there is only one kind of
offspring: SsTt – Sphrical intermediate
80) It has been found that at a certain locus of the human genome, 200 different
alleles exist in the population. Each person has at most __2__ alleles.
81) In Netherlands dwarf rabbits, a gene showing intermediate inheritance produces

three phenotypes. Rabbits that are homozygous for one allele are small rabbits;
individuals homozygous for the other allele are deformed and die; heterozygous
individuals are dwarf. If two dwarf rabbits are mated, what proportion of their
offspring should be dwarf? Please present the Punett table used to answer the
question!
½ are dwarfs, ¼ dies and ¼ are small – 1/3‫ גמדים ו‬2/3‫האם להתייחס ביחסים למי שמת? או ש‬
?‫קטנים‬

A A
A AA Aa
a Aa Aa
82) If the same allele has two or more phenotypic effects, it is said to be
Pleiotropy
83) A mutation at a single locus causes a change in many different characters. This
an example of a(n) __ pleiotropic __ effect.
84) A dominant allele K is necessary for normal hearing. A dominant allele M on a

different locus results in deafness no matter which other alleles are present. If a
kkMm individual is crossed with a Kkmm individual, ___50__ percent of the
offspring will be deaf. Please show the Punett table used to answer the question!
kM km
Km KkMm Kkmm
85) When in a dihybrid cross black, straight-winged Drosophyla is crossed to a

double-recessive brown, curly-winged fly, the frequency at which black curly-
winged and brown straight-winged flies are seen in the progeny is called the _
recombination __ fraction.
86) A human male’s genotype is Hemizygous for a trait showing sex linkage.
87) A(n) __ Heritable __ trait is one that can be passed from one generation to
another.
88) The diagram shows a pedigree. In generation II, female number 5 marries a man
and has three children. Based on these results, one can conclude that the mother
is carrier for the trait, and the treat shows x-linked
inheritance.
89) A(n) _character_ is an observable feature, such as flower color; a(n) __trait__ is a
particular form of a character, such as a white flower.
90) A cross between two parents that differs by a single trait is a(n) _ monohybrid _
cross.
91) When a cross is made and a trait disappears in the F1 generation, only to
reappear in the F2, the trait is probably _ recessive trait _.

92) The physical appearance of a character is the _phenotype_, whereas the genetic
constitution is the _genotype_.
93) A(n) _gene__ is a portion of DNA that resides at a particular locus or site on a
chromosome and encodes a particular function.
94) The region of the chromosome occupied by a gene is called the _locus_.
95) A cross between two heterozygous parents that differs by two independent traits
is a(n) _ Dihybrid _ cross.
96) To determine the overall probability of independent events, one should _ multiply _
the probabilities of the individual events.
97) To determine the probability of an event that can occur in two or more different
ways, one should _sum_ the individual probabilities.
98) Mendel’s laws of inheritance can be applied to human genetics through the study
of _ Pedigree _.
99) One particular allele of a gene may be defined as dominant, because it is present
in most individuals and gives rise to an expected trait, or phenotype.
100) When the expression of one gene depends on the expression of another
gene, the genes demonstrate _ Epistasis/complementary _.
101) Geneticists make use of __recombinant_ frequencies to create genetic maps

that show the arrangement of genes on a chromosome.
102) A female that is heterozygous for a recessive sex-linked character is a carrier.
103) Draw a sample pedigree with three generations in which the maternal
grandmother and paternal grandfather of a girl are carriers of a rare recessive
autosomal trait. (a) What is the probability that the father in the second generation
will be a carrier of this trait? (b) What is the probability that the grandchild with
these grandparents would have the disease? Please explain your answer!
1 2 3 4
I 1
1
II 1 2
III 1
We know that I1, I3 are carriers: Aa, since it’s a rare disease and I2, I3 are not affected we
can assume that their genotype is AA.
The probability that II-1,II-2 will be carriers is ½ (AaXAA). Is they are carriers there is a
chance of ¼ that III-1 wil be affected. Overall: ½ * ½ * ¼ = 1/16

104) You are a genetics counselor who is working with a 21-year-old pregnant
woman who has just discovered that her father has Huntington’s chorea, a rare
dominant autosomal trait. This disease usually develops in middle-aged
individuals, so people carrying this trait do not find out they have this genetic
disorder until midlife. (a) What is the probability, that the child she is carrying will
develop Huntington’s chorea? (Assume that her husband’s family has no history
of Huntington’s chorea.) (b) What is the chance that she has Huntington’s
chorea? Please explain your answer!
Since the disease is rare we can assume that her father is Aa and her mother is aa
The chance that she is a carrier is 50%, her husband is aa so their child has a 50 %
chance of developing the diseas
105) Coat color in mice involves the effects of multiple gene interactions. If a mouse
has two recessive alleles (aa) for coat color, it is always albino no matter what the
genotype is for the other genes involved in coat color. This is an example of
recessive epistasis
106) In many animals, including humans, sex is determined by a single

chromosome, or by a pair of them. Both males and females have two copies of
each of the rest of the chromosomes, which are called autosomal
chromosomes? Homologous chromosomes?.
107) You are examining three different genes, a, b, and c. They all reside on the
same chromosome and you want to know the order of the genes along the
chromosome. You determine that genes a and b are 10 cM apart, b and c are 2
cM apart and that a and c are 8 cM apart. What is the order of these genes?
Why? Please explain your answer!
We will start with the closest pair: b-c which are to cM apart. a has two options, in the
right side of c ar on the left side of b. if we place it on the left side knowing that it is 8 cM
away from c, we will get that it’s only 6 cM away from b which conflicts with the a-b
distance (10 cM). The order is : b-c-a
108) In humans, spotted teeth are caused by a dominant sex-linked gene. A man
with spotted teeth whose mother had normal teeth marries a woman with normal
teeth. Therefore, none of their children will have normal teeth.
109) Using Punnett squares, show that for typical dominant and recessive
autosomal traits, it does not matter which parent contributes the dominant allele
and which the recessive allele. Cross true-breeding tall plants (TT) with true-
breeding dwarf plants (tt).
Parent 1: TT, parent 2: tt

T T
t Tt Tt
t Tt Tt
Parent 1: tt, parent 2: TT

t t
T Tt Tt
T Tt Tt

110) A new student of genetics suspects that a particular recessive trait in fruit flies
- dumpy wings (dp) which are somewhat smaller and more bell-shaped than the
wild type - is sex-linked. A single mating between a female fly with dumpy wings
and a male fly with wild-type wings (Dp) produces three dumpy-winged females
and two wild-type males in the F1 generation. On the basis of these data, is the
trait sex-linked or autosomal? What were the genotypes of the parents? Explain
how these conclusions can be reached on the basis of so few data.
Since we know the trait is recessive the parental genptypes are:
female: XdpXdp
Male: XDpY
As females get one X from each parent, if the trait is sex linked no affected females
should have appear. This trait is autosomal.
111) In Drosophila melanogaster, the recessive allele p, when homozygous,

determines pink eyes. Pp or PP results in wild-type eye color. Another gene, on
another chromosome, has a recessive allele, sw, that produces short wings when
homozygous. Consider a cross between females of genotype PPSwSw and
males of genotype ppswsw. Describe the phenotypes and genotypes of the F1
generation and of the F2 generation produced by allowing the F1 progeny to mate
with one another.
P: PPSwSw X ppswsw
F1:PpSwsw – wild type eye color, wild type wings
PpSwsw X PpSwsw
F2:
PSw Psw pSw psw
PSw PPSwSw PPSwsw PpSwSw PpSwsw
Psw PPSwsw PPswsw PpSwsw Ppswsw
pSw PpSwSw PpSwsw ppSwSw ppSwsw
psw PpSwsw Ppswsw ppSwsw ppswsw
Wild type eye color, wild type wings – 9/16

Wild type eye color, short wings – 3/16
Pink eyes, wild type wings – 3/16
Pink eyes, short wings – 1/16
112) On the same chromosome of Drosophila melanogaster that carries the p (pink
eyes) locus, there is another locus that affects the wings. Homozygous
recessives, bb, have blistery wings, while the dominant allele B produces wild-
type wings. The P and B loci are very close together on the chromosome; that is,
the two loci are very tightly linked!
a) For the cross PPBB ppbb, give the phenotypes and genotypes of the F1
and of the F2 generations produced by interbreeding of the F1 progeny.
b) For the cross PPbb ppBB, give the phenotypes and genotypes of the F1
and of the F2 generations. For the cross of PPbb ppBB?
PPBB X ppbb  PpBb
PpBb X PpBb  ‫אם הם ככ צמודים לא אמורים לקחת בחשבון קרוס אובר? או שסתם‬
?‫ציינו את זה‬
PB Pb pB Pb

PB PPBB PPBb PpBB PpBb
Pb PPBb PPbb PpBb PPbb
pB PpBB PpBb ppBB PpBb
pb PpBb Ppbb ppBb ppbb
Phenptypic ratio : 9:3:3:1 wt eyes wt wings, wt eyes blistery wings, pink eyes
wt wings, pink eyes, blistery wings
PPbb X ppBB  PpBb

F2 ratio is the same as the table above
113) In Drosophila melanogaster, white (w), eosin (we), and wild-type red (w+) are
multiple alleles at a single locus for eye color. This locus is on the X chromosome.
A female that has eosin (pale orange) eyes is crossed with a male that has wild-
type eyes. All the female progeny are red-eyed; half the male offspring have eosin
eyes, and half have white eyes.
a) What is the order of dominance of these alleles?
b) What are the genotypes of the parents and progeny?
The females phenotype is XeX- and the males phenotype is Xw+Y.
All the females have red eyes, we know they have one X chromosome from father
and the other from the father so their genotype is Xw+X- that means that the (w+)
allele is dominant over the other alleles.
The males receive the Y chromosome from their father and x from their mother.
Half are XeY – eosin and the others are XwY – white. Know we know that the0
mother’s second allele is (w) and since her eye color is eosin, (we) is dominant
over (w
w+>we>w
Mother: XeXw
Father: Xw+Y
114) Red-green color blindness is a recessive trait. Two people with normal vision
have two sons, one color-blind and one with normal vision. If the couple also has
daughters, what proportion of them will have normal vision? Explain.
Color blindness is x-linked recessive trait. Since the father is not affected his
genotype is: XAY, and since the mother is not affected yet has a color blind child,
she is a carrier: XAXa. Their daughter receives X chromosome from each parent
so that some will be carriers and some won’t yet no daughter will be color blind.
115) A mouse with an agouti coat is mated with an albino mouse of genotype aabb.
Half of the offspring are albino, one-fourth are black, and one-fourth are agouti.
What are the genotypes of the agouti parents and of the various kinds of
offspring? For which kind of gene interaction would explain these results?
This is an example for recessive epistasis. One gene (A) masks the phenotype of
the other gene (B) when it appears in it recessive form (aa)
Agouti: A-B-
Black: A-bb
Albino: aa—
We know that one parent is aabb, we must have an A so that other colors could
form, and we must have another a so that the albino type could be formed. Same
for B – the presence of B will allow the agouti color, the presence of b will allow
the black color.
Parents: AaBb X aabb

F1:
AB Ab aB ab
Ab AaBb (agouti) Aabb (black) aaBb (albino) Aabb (albino)
116) The disease Leber’s optic neuropathy is caused by a mutation in a gene

carried on mitochondrial DNA.
a) What would be the phenotype of their first child if a man with this disease
married a woman who did not have the disease?
b) What would be the result if the wife had the disease and the husband did not?
When a disease is mitochondrial inherited, it will pass on to future generations
only if the mother is sick, because all of the mitochondria of the initial zygote
are inherited from the mother (there are no mitochondria in the male sperm).
The phenotype of a couple's first child when the father is sick and the mother
is healthy will be that the child won't express the disease.
b) When the woman has the disease, all of her children, male and female, will
have it as well.
117) Please draw a crossing experiment to illustrate Mendel’s laws. What are
Mendel’s laws?
Mendel's first law (the principle of segregation): in the formation of gametes, the
pairs of genes are separated, and each gamete is equally likely to contain either
member of the pair
Mendel's second law (the principle of independent assortment): the segregation of
one pair of alleles does not affect the segregation of another pair of alleles during
the formation of gametes.
How many genotypes and in what frequencies are present in the F2 generation of
a typical dyhibrid cross? (Use the multiplication rule to calculate genotype
frequencies!)
In a typical dihybrid cross we examine the progeny of parents that differ in two
contrasting traits.
P generation: WWGG x wwgg
F1 generation: all heterozygous for both traits WwGg
F2 generation will present a 9:3:3:1 phenotype ratio
F2:
WG Wg wG wg
WG WWGG WWGg WwGG WwGg
Wg WWGg WWgg WwGg Wwgg
wG WwGG WwGg wwGG wwGg
wg WwGg Wwgg wwGg wwgg
118) John and Martha are thinking about having children, but John’s brother has a
rare autosomal disease, an enzyme defect, and Martha’s grandmother also had
the same disease. Martha has a sister who has three children, none of whom
have the disease. What is the probability, that John and Martha’s first child will
have the disease?
Since the defect is in the enzyme, we can conclude that the disease it recessive.

?
.‫המספור הוא משמאל לימין‬
I-1 is sick: aa
I-2 is probably AA since it’s a rare disease
II-4 (their daughter) is a carrier:Aa
II-3 (her husband): AA
II-1,II-2: Aa
III-3: aa
III-2: has a 2/3 chance to be a carrier
III-3 has a ½ chance to be a carrier
Their child has : 2/3 * ½ * ¼ = 1/12 of being sick
119) Please explain the term epistasis. Describe at least one example, with the
appropriate crossing experiment (genotypes, ratios of phenotypes)!
See question 10,115 (you can also cross AaBb X AaBb)
120) Please explain what is the connection between variable gene expression and
penetrance?
Penetrance is the proportion of the population with a certain genotype that will
exhibit the associated phenotype.
Expressivity is the degree to which a phenotype is expressed (in other words: the
severity of the expression). The expressivity depends on the penetrance.
121) Please explain the meaning of the following terms: (a) phenocopy; (b) genetic
heterogeneity (examples are required)!
a. phenocopy- a phenomenon in which the environmental conditions mimic
phenotype produced by a gene, for example : Vanessa genus of butterflies who
can change phenotype based on the local temperature or Drosophila
melanogaster that is influenced by enviromental changes such as temperature.
b. Genetic heterogenity –in contrast to pleiotropy, where a single gene may
cause multiple phenotypic expressions or disorders, This is a phenomenon in
which a single phenotype or genetic disorder are caused by any one of the
multiple number of alleles. For example : Alzheimer disease
122) Please draw a crossing experiment to explain the consequence of having

recessive lethal alleles in the genotype of organisms! Do such alleles modify the
mendelian ratios?

Recessive lethal allele-Homozygous- modify the mendelian ratios instead of 3: 1
phenotypic ratio it becomes 2 : 1
An example - Achondroplasis – A common cause for dwarfism. When
homozygote recessive it’s leathl
A a
A AA Aa
a Aa aa
123) Using a concrete example, please explain the meaning of pleiotropy!

A single gene controlling or influencing multiple (and possibly unrelated) phenotypic
traits.
Example:The human disease PKU (phenylketonuria). This disease can cause mental
retardation and reduced hair and skin pigmentation, and can be caused by any of a large
number of mutations in a single gene that codes for an enzyme (phenylalanine
hydroxylase) that converts the amino acid phenylalanine to tyrosine, another amino acid.
124) In case of incomplete dominance, what are the expected genotype and
phenotype ratios in the F2 generation of a typical mendelian cross? Please show
the exact genotypes present in the P, F1 and F2 generations!
With incomplete dominance, a cross between organisms with two different phenotypes
produces offspring with a third phenotype that is a blending of the parental traits.
P: RRxrr
F1:Rr
F2:RrxRr
R r
R RR Rr
r Rr rr
Ratio : 1:2:1
125) In an organism the autosomal B allelel is required for eye color production.
The unlinked autosomal recessive s causes bright scarlet eyes. Thus, we have
the following correspondences between genotypes and phenotypes:
SS BB: red eyes (wild type)
ss BB: scarlet eye
SS bb : white eye
ss bb : white eyes
What kind of inheritance pattern is this? Explain your answer! Construct a
hypothetical biosynthetic pathway showing how the gene products interact!
This is recessive epistasis. When b is in its homozygote recessive form, it masks the
phenotype of the S.

126) Please explain the meaning of the term epistasis (gene interaction)! Please
mention at least one example(complete with genotypes, phenotypes, ratios) to
illustrate your explanation!
Epistasis is when one gene masks on the expression of another gene; an example for
recessive epistasis is in the question above.
127) The unit of genetic distance of genes is …cM...., which is experimentally

determined by measuring the ……rate of recominantiom……. in genetic crosses.
128) Define the term ’linkage group’.

Linkage group is a group of genes that are located close to each other on the same
chromosome and tend to be transmitted together.

129) What is the relationship between the distance of genes and the probability of
recombination?
Probability of recombination is equal to the distance of gene in cM
130) Show a crossing experiment, with Punnett square, that is consistent with a
genetic distance of 10 cM between two genes.
AaBb X aabb
AB/ab
AB Ab aB ab
Ab AaBb Aabb aaBb aabb
Parental – AaBb, aabb: 90% of offspring are parental

Recombinant – Aabb, aaBb : in total, 10% of offspring are recombinant
131) What is the relative localization of the linked genes compared to the ones that
behave independent?
The distance between linked genes can’t exceed 50cM.
Independent genes can be 50cM (and above) apart.
132) Explain why an individual of AaBb genotype produces the following gametes:
AB 9%, Ab 41%, aB 41%, ab 9%.
The distance between A-B is 18 cM, AB and ab are recombinant gametes. The
conformation is Ab/aB
133) Create a chromosome map with the arrangement of three genes using the
following experimental data. Recombination between A and B: 3.5%;
recombination between A and C: 1.5%; recombination between B and C: 5%.
B-A-C
134) In a human family two sons were born from healthy parents. One of them
suffered from both hemophilia and color blindness, the other was color blind only.
Explain.
Let’s consider this case:
Mother XHcXhC
Father XHCY
H is a healthy allele for hemophilia, C is the healthy allele for color blindness.
First son: XHcY – only color blind
Second son: XhcY – color blind and hemophilia
The mother produced parental gametes: XHc,XhC and recombinant gametes: XHC,Xhc
135) What cell cycle event and in which phase causes genetic recombination?
In the crossing over of homologous chromosomes in Anaphase I
136) What is the difference between the effects of single and double crossing
overs?
A single crossing over can create to new gametes whereas a double crossing over MAY
cancel the first crossing over, no new gametes will be created
137) What is the maximum value of recombination percentage between two loci?
Compare this value with the percentage of new (i.e. not parental) combinations in
the case of independent genes.
The value of recombination percentage between two loci cannot exceed to 50%. Any
value over 50 will present independent genes

138) How can you distinguish between the parental type and the recombinant
progeny, if you don’t know the original coupling of linked alleles of two genes in
the parents?
The percentage of the recombinant gametes has to be below 50%
139) Studying genes on the same chromosome, which genotypes are more
abundant in the progeny: the parental types or the recombinants? Why?
In case the genes are linked, the parental gametes will be more abundant since they will
be presented in more than 50% of the offsprings – linked genes are defined as being less
than 50cM apart. In case of independent genes, there will be an equal display of
genotypes due to independent assortment
140) The recombination frequency of genes A and B is 2%. Are they linked on the
same chromosome?
Yes, the genes are very close to each other – 2cM
141) The recombination frequency of genes A and B is 5%. Are they linked on the
same chromosome?
Yes, the genes are very close to each other – 5cM
142) The recombination frequency of genes A and B is 10%. What is their distance
expressed in cM?
10cM
143) The recombination frequency of genes A and B is 40%. Can we take it for sure
they are linked on the same chromosome? Explain.
144) The recombination frequency of genes A and B is 60%. What is probable: are
they linked on the same chromosome or not? Explain.
145) You have determined the cM distances of three genes as follows: A–B 2 cM,
A–C 5 cm, and B–C 7 cM. What is their order on a chromosome?
B-A-C
146) You have determined the cM distances of three genes as follows: A–B 2 cM,
A–C 5 cm, and B–C 3 cM. What is their order on a chromosome?
A-B-C
147) Mendelian genetics. True breeding is a kind of breeding in which the parents with
a particular phenotype produce offspring only with the same phenotype.
148) Mendelian genetics, monohybrid cross. True breeding parents are crossed in
the P generation. What do you expect in the F1 generation? Which genotype and
phenotype?
F1 generation will have the same phenotype as their parents yet the genotype may
match only one parent (AA X Aa/ AA)

149) Mendelian genetics. True breeding parents are crossed in the P generation.
What do you expect in the F2 generation of a monohybrid cross? Which genotype
and phenotype?
Let’s assume that the parents are AA X Aa.
F1: AA/Aa as well
F2: possible crosses- AA X AA  AA
Aa X AA  Aa/AA
Aa X Aa  AA, Aa, aa
150) Mendelian genetics, dihybrid cross. True breeding parents are crossed in the
P generation. What do you expect in the F1 generation? Which genotypes and
phenotypes?
P: AABB X AaBb
F1: AABB/AaBb
P generation. What do you expect in the F2 generation? Which genotypes and
phenotypes?
P and F1 are as shown in the question above.
F2 possible crosses: AABB X AABB  AABB
AABB X AaBb  AABB/AaBb
AaBb X AaBb  phenotype ratio is 9:3:3:1 as always..
152) Mendelian genetics, monohybrid cross. True breeding parents are crossed in
the P generation. What do you expect in the F1 generation? Which genotype and
phenotype? Has the female or the male character of the crossed individuals any
influence on the result?
Phenotypes and genotypes are shpwn in 148.
The parents have no influence as shown in 109
P generation. What do you expect in the F2 generation? Which ratios of
genotypes and phenotypes? Construct Punnett square.
A punnet square for the last option in question 151:
AB Ab aB ab
AB AABB AABb AaBB AaBb
Ab AABb AAbb AaBb Aabb
aB AaBB AaBb aaBB aaBb
ab AaBb Aabb aaBb aabb
154) In the poultry yard cocks with “pea” combs are crossed to hens with “rose”
combs. What are your expectations regarding the geno- and phenotypes in the F1
and F2 generation? Explain.

155) In the poultry yard hens with “pea” combs are crossed to cocks with “rose”
combs. What are your expectations regarding the geno- and phenotypes in the F1
and F2 generation? Explain.
156) In the poultry yard hens with “pea” combs are crossed to cocks with “rose”
combs and vice versa. What are your expectations regarding the geno- and
phenotypes in the F1 and F2 generation? Will be the results identical or not?
Explain.
157) Different mendelian dihybrid crosses. You expect F2 ratios 9:3:3:1. In fact you
see in some cases 9:7 and in some other cases 9:3:4 ratios. Explain.
9:7 – complementary gene activity
9:3:4 – recessive epistasis
158) AB0 blood group determinations. What is the phenotype of the parents and
what is that of the progeny you expect from a mating of IAIBhh × IAiHh?
H gene – responsible for the formation of the H precursor on the membrane of
RBC. In case of hh genotype, the precursor will not be formed, and the phenotype
of blood type will appear as "O" blood type even if there are alleles for A and B
antigens (because there is no precursor from which A or B antigens can be
formed).
The allele i represents O type.
Parent’s phenotype: O type X A type
IAh IBh
IAH IAIAHh IAIBHh
IAh IAIAhh IAIBhh
iH IAiHh IBiHh
ih IAihh IBihh
A type: ¼
B type: 1/8
AB type: 1/8
O type: 1/2
what is that of the progeny you expect from a mating of IAIBhh × IAiHH?
Parent’s phenotype: O type X A type
IAh IBh
IAH IAIAHh IAIBHh
iH IAiHh IBiHh
A type ½
AB type ¼
B type ¼
what is that of the progeny you expect from a mating of IAIBhh × IBiHH?

Parent’s phenotype: O type X B type
IAh IBh
IBH IAIBHh IBIBHh
iH IAiHh IBiHh
A type ¼
AB type ¼
B type ½
what is that of the progeny you expect from a mating of IAIBhh × iiHh?
Parent’s phenotype: O type X O type
IAh IBh
iH IAiHh IBiHh
ih IAihh IBihh
A type ¼
B type ¼
O type ½
what is that of the progeny you expect from a mating of IAiHh × IBiHh?
Parent’s phenotype: A type X B type
IAH IAh iH ih
IBH IAIBHH IAIBHh IBiHH IBiHh
IBh IAIBHh IAIBhh IBiHh IBihh
iH IAiHH IAiHh iiHH iiHh
ih IAiHh IAihh iiHh iihh
AB type 3/16
A type 3/16
B type 3/16
O type 7/16
163) Rh blood group determinations. DD × dd. What is the phenotype of the two
members of the mating described here? What types of children can they have?
Can any of their children handicapped? If no, why not? If yes, in which aspect?
Parent’s phenotype: Rh+, Rh-
First child will be Rh+ (Dd)
In case the mother is dd (Rh-)
During pregnancy, when a mother is Rh-(doesn't have the Rh antigen) and the
fetus is Rh+, there can be an immune reaction of the mother's immune system
towards the fetus. In the first pregnancy, the mother does not have Rh antibodies
and therefore her immune system will not response against a Rh positive fetus.
Nevertheless, during a second pregnancy of Rh negative mother with Rh positive
fetus, the mother's body has Rh antibodies (the mother's body "remember" the Rh

antigens from the previous pregnancy), and in this time the mother's body can
initiate an immune response.
Second child: as described, the antigens activates the immune system, the
newborn has hemolytic disease
164) Rh blood group determinations. Dd × dd. What is the phenotype of the two
Parent’s phenotype: Rh+, Rh-
First child may be Dd (Rh+) – 50%, or dd (Rh-) – 50%
According to the explanation above, in case the mother is Rh- and her first child
was Rh+ the next child may have hemolytic diseas
165) Rh blood group determinations. Dd × Dd. What is the phenotype of the two
Both parents are Rh+
Their children can be Rh+ (3/4) or Rh- (1/4)
No handicapped children
166) What is the mode of transmission of phenylketonuria? Explain.

PKU is autosomal recessive
167) What is the mode of transmission of Huntington disease? What is the nature of
the mutation?
Autosomal dominant mutation
168) What is the mode of transmission of familial mental retardation?

Recessive X-linked
169) What is the similarity and the difference between hemophilia A and hemophilia
B?
Hemophilia A is an inherited deficiency in clotting factor VIII,[1] which causes increased
bleeding and usually affects males.
Hemophilia B is a blood clotting disorder caused by a mutation of the Factor IX gene,
leading to a deficiency of Factor IX. It is the second most common form of haemophilia,
rarer than haemophilia A
170) The defect of blood clotting factor VII is mainly based on compound
heterozygosity. Is that abnormality a dominant or a recessive illness? Explain.
Deficiency is rare (congenital proconvertin deficiency) and inherits recessively. Factor VII
deficiency presents as a hemophilia-like bleeding disorder
171) What is the molecular basis of the Himalayan coat color of rabbits?
he Himalayan color is pure white with dark “points”; that is, the nose, ears, feet, and tail
are colored while the rest of the bunny is white. This is caused by a gene that is
commonly called the “Himalayan gene”, symbolized by the letters ch.

172) Why is the Himalayan coat color of rabbits recessive to the wild type allele?

Chapter 8
1) Describe the genetic background of the discontinuous traits.

Mendelian monogenic determination of phenotypic traits
These genes are called major genes
The gene effect or genotype can be deduced from the phenotype
2) Describe the genetic background of the continuous traits.

Non-Mendelian "polygenic" determination of phenotype. These genes are
called minor genes. The gene effect cannot be deduced from the phenotype.
3) Why do we prefer to use „multifactorial determination” instead of „polygenic

inheritance”.
Because there are usually 2 factors to take into account when we talk about
traits, genes and environmental factors. If we only use the term polygenic
inheritance, that means we forget the effect of environmental factors in the
determination of discontinuous traits.
4) What can you tell about the genetics of a trait which shows normal (Gaussian)
distribution in the population?
The same characteristics as for the continuous traits. Mendelian monogenic
determination of phenotypic traits. These genes are major genes. The gene
effect can be deduced from the phenotype.
5) What are meristic (countable) traits? Give example.

A trait in which the phenotype is determined by counting. For example number
of ears on a stalk of corn or number of eggs laid by a hen.
6) What is the genetic determination of threshold traits?

Polygenic inheritance.
7) Give three examples of human threshold traits.

Spina bifida, congenital dislocation og the hip, cleft lip and/or palate, pyloric
stenosis.
8) Are common complex diseases determined by monogenic way or by polygenic

systems? Give three human examples.
Polygenic. Hypertonia, hyperlipidemia, familial hypercholesterolemia, diabetes
mellitus.
9) Give a graphical explanation of the threshold model.

Chapter 8
10) The heritability of a trait is 0.5. What can you tell about that value regarding
the genetic background of the trait concerned?
H value of 0.5 is considered a trait with high heritability, most of the variance
for the trait is genetic. The diverstiy of the different phenotypes that we can
observe in populations, is due mainly to the diversity of genotypes (high
number of alleles)
NB: ” Heritability is the proportion of phenotypic variation in a population that is due to
genetic variation between individuals. In easier terms, for a given trait, for exemple
colour of the hair, it tells us if the difference of this trait (colour of the hair) between
individuals comes from a wide variety of environments (different degrees of exposure
to the sun) or from a wide variety of alleles (100 different alleles, each coding for one
specific color)
Saying that most of the variance for the trait is genetic is not the same as
saying that the trait is mostly genetically determined; the trait may, in fact, not be
influenced much by the genes at all, but still happen to have a diversity of genotypes
in the population and not much environmental variation”.
11) What does the term QTL (quantitative trait locus) mean?
A locus segregating for alleles that have different, measurable effects on the
expression of a quantitative trait.
12) Do the two expressions: „minor gene” and „major gene” refer to the size of
genes? Explain.
No, it refers to their effect in the expression of the phenotype. Minor genes are
involved in polygenic determination of a phenotype. Major genes are involved
in monogenic determination of a phenotype.
13) List three human developmental abnormalities (malformations) of multifactorial

origin.
Spina bifida, congenital dislocation of the hip, cleft lip and/or palate, pyloric
stenosis.
14) Some estimations tell us that the heritability of IQ (intelligence quotient) is

between 0.6 - 0.8. How could you explain this statement to a layman?
It means that when you observe in a population, the diversityof intelligence
quotients that you can find is mainly the due to the diversity of alleles coding
Chapter 8
for the genes expressing th IQ rather than to the diversity of environments of

people.
15) Explain the term „risk gene” or „liability gene”.

When different forms of a gene are known to be associated with different levels
of risk for a specific health problem.
16) Describe “threshold traits”. Give example.

A trait with a continuously distributed liability or risk, for example spina bifida,
congenital dislocation og the hip and cleft lip and/or palate.
17) The development of quantitative traits is typically controlled not only by

........................, but also by the .................................. , thus regarding their
determination they are called ................................... .
genes, environment, multifactorial.
18) Is the frequency of the congenital dislocation of the hip the same in the two
sexes? If not, how could you explain the difference?
19) Define the intelligence quotient (IQ).

A score derived from one of several different standardized to assess
intelligence.
20) _______________________ is trait that has only two, or a few, phenotypic

classes, but inheritance is determined by the effects of multiple genes acting together
with the environment.
Threshold trait
1) In genetic analysis, the _complementation__ test is used to determine whether two
recessive mutations that cause similar phenotypes are alleles of the same gene.
2) Transposable elements can cause mutation by two basic mechanisms. Name these
mechanisms.
Mechanism of transposition by cut-and-paste transposable elements
?Intramolecular recombination between repeat sequences
3) Define nonsense mutations.

nonsense mutation is a point mutation in a sequence of DNA that results in a
premature stop codonusually results in a nonfunctional protein product
4) Describe fragile-X syndrome? What is the genetic basis of the syndrome?
Fragile-X is a genetic syndrome that is the most widespread single-gene cause
of autism and inherited cause of mental retardation among boys.
Fragile X syndrome is associated with the expansion of the CGG trinucleotide
repeat.
5) Describe “gain of function” mutations.

Gain of function refers to the generation of a mutant protein with a new function
or an enzyme that produces a new product
6) What is the genetic background of xeroderma pigmentosum? How is it inherited? What

kind of cellular process is defective in this condition?
Xeroderma pigmentosum, is an autosomal recessive genetic disorder of DNA
repair in which the ability to repair damage caused byultraviolet (UV) light is
deficient
nucleotide excision repair (NER) enzymes are mutated, leading to a reduction in
or elimination of NER
7) Describe the Ames test.

See question 18
8) Define silent mutations.

Silent mutations are DNA mutations that do not result in a change to the amino
acid sequence of a protein(due to the redundant charchtar of the codons), or
that do result in amino acid change but do not result in radically different
properties of the changed amino acids.
9) The sketch below depicts the rough structure of a hypothetical transmembrane receptor
protein, the product of the wild type HYTMRP gene. (The N-terminal part is the ligand
binding domain on the extracellular surface, the C-terminal displays enzymatic activity in
the cytoplasm.) The HYTMRP gene suffers a frameshift mutation near the 5' end. What
can be the consequence of that in the protein’s structure and/or function?
Sketch?
10) Explain the term “missense mutation”.
Ch9 Mutation & repair 1/4

missense mutation is a point mutation in which a single nucleotide is changed,
resulting in a codon that codes for a different amino acid. This can render the
resulting protein nonfunctional
11) The pedigree shows inheritance of myotonic dystrophy (DM) in a family. How is the
disease inherited?
The lower part shows the result of Southern blot with the DNA of family members. What
can be concluded from this picture about the molecular nature of the mutation? (The 9 and
10 kb bands correspond to the normal alleles.)
The disease is X-linked dominant.

We can conclude that 10kb is from the mother and 9kb from the father. Enough?..
12) What types of mutations can be revealed by microscopical methods?
?
13) What can be the result of the presence of a non DNA base (Uracyl, Hypoxanthin,
Bromouracyl) during replication.
When a non DNA is incorporated into the DNA, it is most likely to pair with
adenine; however, it can spontaneously shift into another isomer which pairs
with a different nucleobase, guanine. If this happens during DNA replication, a
guanine will be inserted opposite the base analog, and in the next DNA
replication, that guanine will pair with a cytosine. This results in a change in one
base pair of DNA, specifically a transition mutation.
When uracil is inserted it can be removed by DNA uracil glycosylase.
14) How can a repair mechanism cause mutations?

In case of DNA damage, where the repair mechanism recognizes and excise the
mistake, the repair machinery may not read the complementary strand accurately
and, as a consequence, will create mutations by introducing incorrect bases.
15) What does DNA damage mean and how is it related to mutation? Provide examples!
DNA damage means an error in the DNA sequence, it can be caused by depurination
– the bond between the sugar and the base is broken and the base is replaced by
OH, demethylation or deamination, some of these damages can be repaired, even if
the damage is repaired, the repair mechanism may read the complementary strand

not accurately and cause a mutation – an error that will remain in the DNA and after
cell division is permenant, it won’t be recogniozed by the repair mechanism and is
now called a mutation
16) What is the cause of thymine dimmers, and which mechanism is responsible for its repair?
Name a disease that is caused by the failure of this system.
UV light can cause thymine dimmers. Dimers may be repaired by photoreactivation
or nucleotide excision repair.
Xeroderma pigmentosum is a genetic disease in humans in which the nucleotide
excision repair process is lacking, resulting in skin discolouration and multiple
tumours on exposure to UV light
17) Intercalating agents (like acridine) can cause loss of nucleotides in DNA during
replication. What can be the result of such mutation, if the number of affected nuclotides
in a coding sequence is 1? What is the case if the number of lost nucleotides equals 3?
Intercalating agents cause a frameshift mutation in the DNA. On case only one
nucleotide is affected the frameshift is called translational frameshift. The new
poly peptide will create different amino acid creating a new protein. In case of a
frameshift of 3 nucleotides, onlt 1 amino acid will be missing from the protein,
there is still a chance that the protein will function as it should.
18) Name and describe a method to assess mutagenic potential of a substance (e.g. cosmetic,
drug)
Ames test - uses strains of Salmonella that have been altered to make them
more susceptible to mutation than normal Salmonella. To perform the test, the
altered Salmonella strains are combined in a test tube with the chemical of
interest. Because Salmonella bacteria lack the enzymes that animals use to
metabolize chemicals, animal liver enzymes are often added to the test tube.
That way, the test is able to detect what might happen if the chemical entered a
human body. The Salmonella are then transferred to a petri dish to grow for one
or two days. The altered Salmonella used for the test require the amino acid
histidine to grow, and a positive result in the test is indicated when, in response
to mutation, the Salmonella no longer require histidine to grow.
19) Two individuals suffering in xeroderma pigmentosum (both homozygous recessive) have
a child who is free of the disease, explain the phenomenon.

20) DNA polymerase has 3'- 5' exonuclease activity known as...
Reverse transcription
21) What is the molecular background of dynamic mutations (mutations that gain severity in
each generation)?
Dynamic mutation is an unstable heritable element where the probability of
expression of a mutant phenotype is a function of the number of copies of the
mutation

Questions for polymorphisms:
1) Give a definition of genetic polymorphism!

A genetic variation that results in different forms or types of individuals
among the members of a single species. The variant is foound in more
than 1% of chromosomes in general population.
2) List the most important DNA polymorphisms!
Simple tandem repeat polymorphisms (STRP’s) are repeating units of 2-9
base pairs, also known as microsatellites. Used for human identification,
looking at genetic relatedness and DNA typing.
Copy number polymorphisms are alterations of the DNA genome that
results in a cell having an abnormal number of copies of one or more
sections of DNA. They correspond to relatively large regions of the
genome that have been deleted or amplified on a certain chromosome.
E.g. A-B-C-D might be A-B-C-C-D or A-B-D.
3) How would you characterize the microsatellite markers?

Microsatellite are repeating units of 2-9 base pairs, also known as simple
sequence repeats. Used for human identification, looking at genetic
relatedness and DNA typing.
4) How would you characterize the minisatellite markers?

A minisatellite (also referred as VNTR) is a section of DNA that consists of
a short series of bases 10–60 bp.[1][2] These occur at more than 1,000
locations in the human genome.
5) How would you characterize the SNP markers?

SNP’s are polymorphisms which arise via changes of a single nucleotide.
About 10% of the most frequent SNPs were chosen to serve as genetic
markers.
6) What is the relationship between a SNP and a RFLP?

SNP’s and RFLP’s are polymorphisms and can be used as genetic markers.
SNP’s are polymorphisms which arise via changes of a single nucleotide.
RFLP’s are differences in fragment length produced by the presence or
absence of the cleavage sites in DNA molecules. This produces shorter or
longer DNA fragments than witnessed in the population. Both SNP’s and
RFLP’s can be used in DNA typing and screening human DNA for the
presence of potentially deleterious genes e.g sickle cell anemia.
7) What is the role of restriction endonucleases in the RFLP-detection?
Polymorphisms, genetics of blood types & MHC 1/10

Restriction endonucleases is a bacterial enzyme that recognizes specific
double stranded sequence in the DNA at cleaves the double helix at a
nearby site.
This cleavage process produces a collection of fragments whose length
distribution reflects the frequency and localization of the cleavage site.
These fragments can be used in RFLP for further investigation.
8) In what way RFLP can be used in genotyping and diagnosis of genetic diseases?
Using RFLP technique we can analyze the DNA of a patient and conclude
whether a particular mutation is present or absent.
Once the mutation is known, we will cleave the DNA using the appropriate
restriction enzyme and probe. **
9) Describe at least two methods for detection of a microsatellite polymorphism!

Quantitive PCR – a technique that measures the amount of a particular
DNA sequence in a sample.
RFLP – a specific fragment cleavage.**
10) What is DNA fingerprinting?
The minisatellite repeat sequences found in many different
polymorphisms are sufficiently similar to one another to make possible
the detection of many different loci simultaneously by use of one
minisatellite fragment as a probe. Only identical twins show an
indistinguishable pattern, and therefore the simultaneous detection of a
number of minisatellite polymorphisms is called DNA fingerprinting, used
for identity testing.
11) Are there phenotypic changes caused by a SNP in most of the cases?
Sickle cell*
12) If most DNA polymorphisms are not related to phenotypic variations (e.g. diseases), how
could they benefit genetic/medical research?
13) List some important applications of DNA marker investigations!

Genetic markers can be used for studying relationships (gene mapping)
between an inherited disease and its genetic cause and also DNA typing
which is used in criminal investigations. Significance of genetic markers is
used in criminal investigations landmarks along the DNA, thus allow
genetic differences among individual to be tracked.
14) What are the copy number variations? Give some characteristics, too.

Copy number polymorphisms are alterations of the DNA genome that
results in a cell having an abnormal number of copies of one or more
sections of DNA. They correspond to relatively large regions of the
genome that have been deleted or amplified on a certain chromosome.
E.g. A-B-C-D might be A-B-C-C-D or A-B-D.
Genetics of blood groups and MHC
15) What do you mean by a polymorphic locus? Give a short description and list 3 human
examples.
It's location within a gene that has a large number of possible sequences.
An example of a ploymorphic locus would Human Leukocyte Antigen
genes,
??
16) What kinds of genes are responsible for the AB0 blood group? Describe their function and
their relationships to each other.
The ABO blood type is controlled by a single gene (the ABO gene) with
three alleles: i, IA, andIB.
The gene encodes a glycosyltransferase—that is, an enzyme that modifies
the carbohydrate content of the red blood cell antigens
The IA allele gives type A, IB gives type B, and i gives type O. As
both IA and IB are dominant over i, only ii people have type O blood.
A and B express a special dominance relationship: codominance, which
means that type A and B parents can have an AB child
17) Can you consider AB a general recipient and 0 as general donor? Give an explanation.
(Simple yes or no answer is not acceptable.)
In the system of an individual with AB blood type there are no antibodies
for either of the antigens, A or B, because they are both present on the
RBC. Because there are no antibodies for either A or B antigens, an
individual with AB blood type is a general recipient because its body won't
cause an immune response to the transfusion of any blood type (A, B, AB,
O).
On the other hand, individuals that have O blood type is a general donor
because they have no antigens on their RBC, and therefore their RBC won't
be recognized by the immune system of the recipient.
18) What is the chemical nature of AB0 antigens? Where are they located?

The ABO antigens are carbohydrates located on the cell membrane of RBC.
19) Describe the biosynthesis of A and B antigens. What is their common precursor?
The A and B antigens are formed from the same carbohydrate precursor
(H antigen) by the action of enzymes that are encoded from the alleles of
the I gene. The active enzymes modify the precursor into the A and B
antigens.
20) Why are IA and IB dominant over i? What do they code for?
IA and IB alleles are dominant over i because they are the alleles that will
be expressed in case of heterozygous individual to either A blood type or
B blood type. In the molecular level, the IA and IB alleles encodes for active
enzymes that modify the H antigen into A or B antigens, whereas i
encodes for an inactive enzyme.
21) Establish the genotypes of individuals II/5 and II/6 from the pedigree above and describe
it in the format like the following: HHIAIASese. Give an explanation! What kind of gene
interaction is demonstrated on this pedigree?
H gene – responsible for the formation of the H precursor on the

membrane of RBC. In case of hh genotype, the precursor will not be
formed, and the phenotype of blood type will appear as "O" blood type
even if there are alleles for A and B antigens (because there is no
precursor from which A or B antigens can be formed).
Se – responsible for secretion of ABO antigens into the body fluids,
sese genotype will have no ability to secret the antigens.
I gene – responsible for the formation of enzymes that modify the H
precursor.
According to the pedigree, I/1 is a secretor, which means he can be

either Se/se or Se/Se. because some of the II generation are non
secretors, it means that I/1 is a heterozygous (Se/se).

Also we can see that in the II generation we have some "O" blood type,
which means that their genotype is not necessarily recessive (contains
two IO alleles), but there was no precursor to be modifies into A or B
antigens, therefore they have hh genotype, which means that both I/1
and I/2 are heterozygous for the H gene.
From all of the above we can conclude that I/1 is HhIO IOSese, and that
I/2 is HhIBIBsese (most probably that I/2 is homozygous to the IB allele
because all of the II generation is either B type or "O" type, no genuine
O type).
II/5 is "O" blood type, which means she has the hh genotype for the H
gene. She is also a non secretor, which means she is se/se for the
secretion gene. The fact that both parents are homozygous means that
she has IO allele and IB allele. Therefore II/5 genotype is hhIBIOsese.
22) Is H substance (or H antigen) present in Bombay blood group? Explain why! What kinds
of antibodies are present in the serum of a Bombay blood group person?
Bombay blood group is a group in which there is no precursor for the
formation of A or B antigens because they have a genotype of hh for the H
gene, which means that the antigen is NOT formed. Therefore, even if the
alleles for the A and B antigens are present, there is no possibility of
forming them.
A person who have a Bombay blood type have antibodies for both A and B
antigens but also antibodies for the H antigen
23) Describe the genotypes of an Rh incompatible couple. What are the consequences of an
Rh incompatible pregnancy?
Rh incompatible couple is when one partner has the Rh antigen and the
other does not.
During pregnancy, when a mother is Rh negative (doesn't have the Rh
antigen) and the fetus is Rh positive, there can be an immune reaction of
the mother's immune system towards the fetus. In the first pregnancy, the
mother does not have Rh antibodies and therefore her immune system
will not response against a Rh positive fetus. Nevertheless, during a
second pregnancy of Rh negative mother with Rh positive fetus, the
mother's body has Rh antibodies (the mother's body "remember" the Rh
antigens from the previous pregnancy), and in this time the mother's body
can initiate an immune response.

24) In which case(s) can you detect anti-D antibodies in a person’s blood?
The D antigen is one of the most important antigens of the Rh antigen
group. Anti-D antibodies can be detected in a person's blood if the
antigen is NOT present on that person's RBC membrane.
25) The mother has A blood group, the father has B blood group. What are the possible
genotypes and phenotypes of their children? Consider all possibilities!
If both parents are heterozygous:
IB IO
IA IA IB IA IO
IO IB IO IO IO
All blood types are possible to be present on the phenotype, A and B
blood types will have a heterozygous genotype, AB blood type is co-
dominant genotype and O blood type is recessive homozygous.
If both parents are homozygous:

IA IA
IB IA IB IA IB
IB IA IB IA IB
All children will have a co-dominant genotype and will present a
phenotype of both A and B antigens (AB blood type).
If the mother is homozygous and the father is heterozygous:

IA IA
IB IA IB IA IB
IO IA IO IA IO
The children will have either A and B antigens (phenotype) and the co-
dominant alleles of the I gene, or they will have only the A antigen present
(phenotype) and heterozygous alleles of the I gene (one for A and one for
O).
If the mother is heterozygous and the father is homozygous:

IA IO
IB IA IB IB IO
IB IA IB IB IO
The same ratio of phenotype and genotype, only instead of heterozygous
A blood type, there will be heterozygous B blood type.

26) How many loci are responsible for the Rh antigens? What is the chemical nature of the
antigens? Which is the strongest antigen among them?
There are 2 major adjacent gene loci that are responsible for Rh antigens:
the RHD (encodes for D antigen) and RHCE (encodes for C, c, E, e
antigens). Those Rh antigens are transmembrane proteins whose structure
suggests that they are ion channels. The strongest antigen is the D
antigen.
27) What is the meaning of MHC? What are the most important characteristics of MHC loci?
MHC is major histocompatibility complex, a set of molecules that is
designated to help the immune system to distinguish between the
components of the body and foreign components.
The most important characteristics of the MHC proteins are that they are
highly polymorphic (have several alleles to the same gene), they are
polygenic (several genes that encodes for the MHC) and they are co-
dominant expressed.
28) What are the most important characteristics of MHC loci from genetic point of view? List
at least 3.
The most important characteristics of the MHC loci are that they are
highly polymorphic (have several alleles to the same gene), they are
polygenic (several genes that encodes for the MHC) and they are co-
dominant expressed.
29) There are two inbred mouse strains. The MHC genotype of P1 is A1A1, and that of P2 is
A2A2. What is the probability that a skin graft will be accepted
a) if the donor is P1, and the recipient is P2 ………….
b) the donor is P1, and the recipient is F1 …………….

c) the donor is F1, and the recipient is P1…………….
d) Explain:
a) P1 and P2 has no match in their MHC genotype OR phenotype, and

therefore any donation from P1 to P2 will be rejected.
b) The F1 has only 50% of the MHC genotype of P1, and therefore there is
no match between F1 and P1, and the donation will be rejected.
c) the F1 has a 50% match to the P1 (because the F1 has both P1 and P2
genotypes), therefore there is a chance of 1/2 that the graft will be
accepted.
30) There are two inbred mouse strains. The MHC genotype of P1 is A1A1, and that of P2 is
A2A2. What is the probability that a skin graft will be accepted
a) if the donor is P1, and the recipient is F2……………
b) the donor is F2, and the recipient is P1……………..
c) The donor is F1, and the recipient is F2…………….
d) Explain:
a) The F2 has only 50% of the MHC genotype of P1, and therefore there
is no match between F2 and P1, and the donation will be rejected.
b) The F2 has a 50% match to the P1 (because the F2 has both P1 and
P2 genotypes), therefore there is a chance of 1/2 that graft will be
accepted.
c) The F2 and F1 has a full match of MHC genotype, donation won’t be
rejected.
31) What is the chemical nature of class I and class II antigens? Where are they located?
Class I MHC is present on all cells in the body, and their molecules consist
of intracellular (cytosolic) polypeptide chains.
Class II MHC is present mainly on the cells of the immune system, and
their molecules consist of polypeptide chains derived from extracellular
proteins.
32) What is the probability that siblings have completely identical MHC class I alleles, and
what is the probability that they have haploidentity (50% identity)?
Between siblings there is a probability of 25% that they will have
completely identical MHC class I alleles, because there is a chance of 1/2
that two siblings will get the same alleles from one parent, just as there is
a chance of 1/2 that they will get the same alleles from the other parent.

33) In a paternity test the mother has A1,A3, B7, B27 antigens, the child has A2,A3, B8,B27
antigens. Two men has a) A2A4B5B8 b) A1A3B2B7 antigens. Can any of them be
excluded from paternity? Write up the haplotypes of the parents and the child.
The child has A3 and B27 antigens that he got from his mother (both
genes of these antigens are on the same chromosome). That means that
he got the A2 and B8 from his father. Only man (a) has the same antigens,
therefore we can exclude man (b).
Mother haplotype: A3 and B27 on one chromosome, A1 and B7 on the
other.
Father haplotype: A2 and B8 on one chromosome, A4 and B5 on the other.
Child haplotype: A3 and B27 on one chromosome, A2 and B8 on the
other.
34) Describe linkage disequilibrium. Could you give an example of its medical significance?
In population genetics, linkage disequilibrium is the non-random

association of alleles at two or more loci, that may or may not be on the
same chromosome. In other words, linkage disequilibrium is the
occurrence of some combinations of alleles or genetic markers in a
population more often or less often than would be expected from a
random formation of haplotypes from alleles based on their frequencies.
It is not the same as linkage, which is the presence of two or more loci on
a chromosome with limited recombination between them. The amount of
linkage disequilibrium depends on the difference between observed and
expected (assuming random distributions) allelic frequencies.
Example: Human Leukocyte Antigen (HLA) alleles.
HLA constitutes a group of cell surface antigens as MHC of humans.

Because HLA genes are located at adjacent loci on the particular region of
a chromosome and presumed to exhibit epistasiswith each other or with
other genes, a sizable fraction of alleles are in linkage disequilibrium.
35) Describe the meaning of haplotype.

Haplotype means that several alleles reside on a piece of a chromosome
very closely together, so that they are inherited as one unit (as in MHC).

36) Recently MHC (HLA) typing is not done by serological reactions. Please list 3 up-to-date
methods for HLA typing.
Methods for HLA typing:
Cellular typing, gene sequence, phenotyping.

1) It has been found that at a certain locus of the human genome, 200 different alleles exist in
the population. Each person has at most ___2____ alleles.
2) The equations in population genetics p+q=1 and p2+2pq+q2=1 are called ……hardy-
Weinberg principle……….…… ............................. …………….…… .
3) List the criteria of the “ideal” or model population.
-no mutations
-mating is random
-population size is indefinite
-no natural selection- does not affect the survival of particular genotypes.
4) Describe an example when selection can stabilize a relatively high frequency of a harmful
allele in a population.
...‫לא בטוח שזו הדוגמה שהם רוצים אבל זה מה שחשבנו‬
We can look at the migration of the first dark people from Africa to Europe, while in Africa their
dark color was an advantage in Europe , this trait was harmful since they could not produce any
vitamin D which caused them sickness and death. People with bright skin however survived.
5) If 25% of individuals have 0 blood type, and the frequency of IA allele q=0.3, what
fraction of the population belongs to blood type AB?
p=IB.
q=IA. p+q+r=1
r= i (recessive allele)
r2 = 0.25 r=0.5
q= 0.3 p=0.2
AB blood type is 2pq, meaning it is 0.3x0.2x2=0.12 12% in the population
Since AB is heterozygous it still remains 2pq as in the hardy-weinberg equation even
though we have multiple allelism.
6) If 4% of males are color blind, estimate the frequency of color blind women.
Color blindness is an X-linked recessive trait. Homozygous women are color blind. In case of men
one mutant allele is enough for being color blind.
q=0.04 (i recessive allele)
7) The process in which chance determines the direction of unpredictable changes of allele
frequencies in small populations is called ………gene drift……………..
…………………..?
8) What is the difference between random and assortative mating?
Random mating- individuals do not preferentially choose mates with certain genotypes.
Assorting mating - individuals do preferentially choose mates with certain genotypes
9) How does inbreeding affect the frequency of heterozygotes in a population?

Increasing the chance for homozygous genotype.
10) Why are X-linked recessive traits more frequent in males than among females?
Males have only one x chromosome and if they have an effected one it is enough for expression of
the trait while with women 2 x chromosomes are needed to be affected for expression.
Ch9 Population genetics 1/3

11) Define the term `genetic drift`.
Small changes in the frequency of allels from one generation to another. Only present in SMALL
POPULATIONS.
12) The marriage between relatives in a pedigree or in population genetics is called

………………inbreeding………………. …………………………….
13) The most common form of color blindness (deuteranopy/deuteranomaly) known as red-
green color blindness affects 6 % of the male population in the USA. What is the
frequency of the carrier females in the USA?
Color blindness is a sex linked recessive.
With female carriers it has to be a heterozygous (2pq)
q=0.06
p=0.94 2pq= 0.1128
14) A survey revealed that there were 7000 people belonging to blood group 0 in a human
population of 28 000 which was in genetic equilibrium. 5600 people were found to be
heterozygous for blood type B. Calculate the frequencies of the alleles determining AB0
phenotypes.
2pq=5600/28000= 0.1
p=(recessive i)=0.5 (7000/28000-)‫שורש‬
q= (IB)=0.2
r=(IA)=0.3
15) In Europe, about 84 % of the population is Rh+. (DD and Dd are Rh+, dd is Rh-.) How
many percent of the population is heterozygous Dd?
q2=0.16 q=0.4 (q=dd homozygous recessive).
p=0.6 (p=DD)
2pq=(Dd)=2x0.6x0.4=0.48
16) Why, in a random mating population, does the allele frequency of a rare recessive allele
change slowly under selection?
17) In a population the AB0 blood type was studied. 25000 persons out of 100000 had blood
type 0. The frequency of IA was found to be 0.3. How many persons had blood type B?
ii=0.25 i=0.5
IA=0.3
IB=0.2 IBIB=0.04
IBIO=2X0.04X0.5=0.2 all B blood type=0.24
24,000 people have B blood type
18) A population has the following allele frequencies at the AB0 blood group locus: IA,
0.152; IB, 0.129; and I0, 0.719. If you sample 100 persons from this randomly mating
population, how many people would fall into each phenotypic category (blood type A, B,
AB, and 0), assuming a Hardy-Weinberg equilibrium?
A blood type- IAIA+ IAi = (0.152x0.152) +(0.152x0.719)
B blood type- IBIB+IBi = 0.1292 +0.129x0.719
O blood type – ii=0.7192

19) Why is natural selection very inefficient with rare recessive alleles?
Once the recessive allele is hidden in heterozygous the natural selection becomes less efficient in
eliminating this rare allele.
20) Populations maintain harmful alleles at low frequencies as a result of a balance between
selection, which tends to eliminate the alleles, and _mutations__________, which tends to
increase their frequencies.
21) Phenyketonuria is an inborn error of metabolism caused by an autosomal recessive gene.

The frequency of this allele in the population is 0.03. Assuming Hardy-Weinberg
equilibrium, what is the expected incidence of phenyketonuria among the offspring of all
matings in this population?
(0.03)2=0.0009
22) In Europe 0.36% of the females are defective in green sensitivity and 0.04% do not see
red well. What is the frequency of color-vision defective males in this population?

1) What do you mean by loss of function mutation? Give at least 2 examples.
Loss of function is due to deletion, leading to a reduction in gene dosage.
 α-thalassemias (due to deletion of α-globin genes)
 Turner syndrome (monosomy by loss of one X chromosome) page323
2) What do you mean by gain of function mutation? Give at least one example.
Mutations that enhance the normal function of protein or increase production of protein.
 Hemoglobin kempsey (which locks hemoglobin in its high oxygen affinity state, thereby
reducing oxygen delivery to tissue)
 Trisomy 21 (Down syndrome) page325
3) What do you mean by a novel property mutation? Give at least one example.
Change in amino acid sequence causes disease by giving a novel property on the protein without
necessarily altering its normal function.
 Sickle cell disease (due to an amino acid substitution that has no effect on the ability of sickle
hemoglobin to transport oxygen) (page 325)
4) What is the meaning of mutation associated with ectopic or heterochronic gene expression? Give
at least one example.
The mutation includes those that alter the regulatory regions of a gene to cause its inappropriate
expression. Cancer is the most common genetic disease which is frequently due to the abnormal
expression of gene. (page 325)
5) Which steps of gene expression can be affected by mutations? List at least 4 and illustrate each of
them with an example.
6) Briefly characterize globin chains and the hemoglobin from structural point of view.
Hemoglobin, oxygen carrier, contains four subunits (2 αchains &2βchains) and each subunit is
composed of polypeptide chain. Each subunit has 8 helical regions. One of the most conserved
amino acid, His92, is covalently linked to iron of hem. Phe42 is needed for hem binding.
(page326)
Ch11 Hemoglobinopathies 1/5

7) What kind of gene clusters code for the globin chains? How many alpha and beta globin genes do
we have?
The gene for the αand α-like chains are clustered in a tandem arrangement on chromosome
16.There are 2 identical αglobin genes α１and α2. The gene for the β and β-like chains are
on chromosome11. In β-globin gene is only one, and it forms complexes with different genes
such asδ-globin. Genes in both αand βclusters are arranged in the same transcriptional
orientation. (page 327 )
8) How does the place of red blood cell formation is changing during development? What is the
difference between fetal and adult hemoglobin?
In human embryo, the first site of blood formation is the yolk sac.
Liver is the most important red blood cell forming organ in later embryonic life.
In the human adult, the bone marrow is the only place to produce all of red blood cells. Fetal
hemoglobin is predominant in HbF (α2γ2), and adult hemoglobin is HbA2 (α2δ2: about 2%)
and HbA (α2β2. over 95%), and HbF ( less than 1%). (page 327)
9) How can you classify the hemoglobin disesases? Briefly describe these disease categories.
There are more than 400 abnormal hemoglobins have identified, and hemoglobin diseases can be
classified in three classes depending on the clinical phenotype
① Varients that cause hemolytic anemia
② Mutants with altered oxygen transport
③ Varients due to mutations in the coding region that cause thalassemia (page 329)
10) Describe the molecular cause and pathophysiology of sickle cell disease
Abnormality in sickle cell hemoglobin is a replacement of one of 146 amino acids in the βchain of
the hemoglobin molecule. Mutant β-globin subunit can bund oxygen but in deoxygenated blood,
they are only one fifth as soluble as normal hemoglobin. (page 330)
11) A person has the following genotype: HbSHbC or βSβC. How would you describe the phenotype
and the genotype of this person?
This genotype is described as sickle cell haemoglobin C disease. The genotype HbS/HbC
(HbS=hemoglobin S; HbC=hemoglobin C) is the result in beta-globin subunits replaced by
hemoglobin S and hemoglobin C. The patient shows moderate sickle disease.The sickle-shaped cells
can also block small blood vessels, causing pain and organ damage. (websites)
12) Do all beta-globin mutations cause a disease. Explanation is required.

No. Beta-globin mutations are responsible for the hemoglobin beta (HBB) gene, and more than 250
mutations are reported, and some of variations cause no noticeable signs or symptom.
http://ghr.nlm.nih.gov/gene/HBB (couldn’t find from the book)
13) How could you detect the presence of the disease-causing gene (or gene product) in a family, in
which sickle cell disease occurred earlier? Give at least 2 methods and explain their use.
The sickle cell disease occurs by mutations in the hemoglobin beta(HBB) gene, and is inherited in an
autosomal recessive pattern. The common mutations are hemoglobin S(Glu6Val) and
hemoglobin(Glu6Lys).
1.Prenatal diagnosis by chorionic villus sampling (CVS) at ten to 12 week`s gestation obtaining fetal
cells by amniocentesis.
2.Peripheral blood smear; sickle cells, nucleated red blood cells, target cells may be seen.

3. HPLC(high performance liquid chromatography) is very sensitive allowing accurate quantification
of variant hemoglobin at low concentration.
http://www.ncbi.nlm.nih.gov/books/NBK1377/
14) Can the so called Bart’s hemoglobin and the HbH carry oxygen? In which disease do you see
these molecules?
NO.. Both are completely inefficient oxygen carries. Hb Bart syndrome (most severe alpha
thalassemia) results from the loss of all four alpha-globin alleles. HbH disease is caused by the loss
of three out of four alpha-globin alleles. Shortages of alpha-globin inhibit making normal
hemoglobin (abnormal hemoglobin molecules are synthesized instead)
http://ghr.nlm.nih.gov/condition/alpha-thalassemia (+seminar)
15) How is used the electrophoresis of the hemoglobin in the diagnosis of hemoglobinopathies?
By using both alkaline and acid electrophoresis methods, hemoglobin variants are determined by
the migration patterns (speed of electrophoresis). For example, by using PCR, with using specific
primers for detecting either mutant allele or wild type allele, DNA fragments are amplified and
electrophoresis. (Wikipedia, lecture material)
16) Which are the most common human single-gene disorders, and what is the pathophysiological
mechanism of the disease(s).
(not sure!!) Common monogenic disease result from modifications in a single gene are such as
Haemophilia, tay sachs diseases, Fragile X syndrome, Sickel cell anemia, thalassaemia, Huntington`s
disease, and cystic fibrosis.
Fragile X syndrome is one of the most common diseases. The pathophysiological mechanism is as
following. In the human fetal brain, FMR1 mRNA are detected in fetal cholinergic neurons of
hippocampus, but in the fragile X group, disruption of the cholinergic system are observed and
resulted in mental impairment and autism. (couldn’t find from book)
http://www.medmerits.com/index.php/article/fragile_x_syndrome/P5
17) The alpha-thalassemic newborns have severe disorders at birth, while the beta-thalassemics do
not. What is the reason for this difference?
Alpha thalassemia is caused reduction of α-globin production, so the production of hemoglobin is

significantly reduced at birth. Beta-thalassemia results from a reduction in the abundance of β-
globin. β-globin is one of the major adult hemoglobin proteins in red blood cells so, even if the
sever type children appear healthy at birth. (even thoughβglobin can detect early gestiation,
synthesis becomes significant only near the time of birth and to by 3 months of age) (Genetics p
324,327)

18) Make a simple drawing of the molecular event leading to the deletion of an alpha globin gene.
Also give the name of this event.
Most common probable mechanism of α-thalassemia due two delete one α-globin gene as
shown below. Mislignment homologous pairing and unequal crossover: (page 333, 334)
19) In an alpha-thalassemic patient the alpha globin genes were sequenced and no mutation was
found. What can be the cause of the disease in this case?
ATR-X syndrome can be doubted. In this case, both α-thalasmia and syndromic mental retardation
result from mutations in the X-linked ATR X gene, which encodes a chromatin remodeling protein
required for the normal expression of the α-globin complex. (page 334)
20) What is the genetic cause of beta-thalassemia and how is it treated?

δ-globin and γ-globin can be compensate for the reduced amounts of β-globin but δ－and γ-
globin are only 2% of total adult hemoglobin (very limited amounts), so increase their amounts by
activating relating transcriptional factors for synthesis can be possible treatment.
21) Can an intron mutation in the beta globin gene cause a disease? Explain why, or why not.
Yes, for example abnormal acceptor site of intron 1 (AG⇒GG) can be cause a disease (β-
Thalassemia) . This mutation causes abnormalities in RNA splicing, and it decreases the production
of β-globin mRNA.
22) What are the main steps of the maturation (processing) of beta-globin mRNA? What is the
consequence, if one of these steps is missing?
Defect in capping (add cape site at 5ènd) and tailing (polyadenylation of 3ènd ) of β-Globin
mRNA. For example, A patient substitute AAUAAA with AACAAA at 3ènd may minor
fraction of β-globin mRNA is polyadenyated at the normal position.
(Page 340)
23) What kinds of mutations can lead to the synthesis of nonfunctional mRNA? Mention at least 3.
a) Nonsense mutations create stop codon.
b) In case of 1 nucleotide deletion, frameshift will cause an early stop codon.
c) Nonsense mutations often lead to the degradation of nonfunctional mRNA
(seminar maerial)

24) Is it possible that a missense mutation in a beta globin exon causes abnormal splicing, too?
Explain.
Yes it is possible. The missense mutation (Glu26Lys) in codon 26 in exon1 activates a cryptic
donor splice site in codon 25. The splicing defect is demonstrated below and the change results from
a single mutation.
(page 338-339)

1) What do you mean by housekeeping gene/protein and tissue specific gene/protein?
Housekeeping proteins are present in virtually every cell and have fundamental roles in
the maintenance of cell structure and function.
Tissue-specific specially proteins are produced in only one or limited number of cell
types and have unique functions that contribute to the individually of the cells in which
they are expressed.
The proportion of genes coding these proteins in RNA is different. One which coding the
former(90%) is major than the latter(10%).
So the disease caused by mutation in housekeeping gene happens more frequently.
2) Give an example for a mutation in a housekeeping gene and a tissue specific gene. Also
name the diseases what they cause.
Phenylketonuria is due to the absence of phenylalanine hydroxylase activity in the liver,

but the brain, not the liver, is damaged by the high blood levels of phenylalanine due to
the lack of hepatic phenylalanine hydroxylase.
3) Why are the clinical phenotypes of genetic disesases so variable?
Variation due to one of three types of geneticvariation:

1. Allelic heterogeneity,2. locus heterogeneity , or 3.the effect of modifier genes.
⇒1.due to presence of multiple alleles at a locus.
⇒2.arise from the association of one or more than one locus with a specific clinical
condition, a situation termed locus heterogeneity
⇒3.phenotypic variation can be due to environmental factors or to the action of other
genes, termed modifier genes.
4) What is the molecular cause of classical phenylketonuria, how is it inherited, what are its
main symptoms?
The abnormalities that lead to an increase in the blood level of phenylalanine

hydroxylase deficiency or phenylketonuria, illustrate almost every principle of
biochemical genetics of relevance to enzyme defects.
it is an autosomal recessive disorder of phenylalanine catabolism.
Symptoms : mental retardation,
5) How is the classical PKU diagnosed and treated?
A droplet of blood is obtained from a heel prick, dried on filter paper, and sent to central
laboratory for analyzing of blood phenylalanine levels and of the phenylalanine-to-
tyrosine ratio.
Classic PKU (>1mM)
Dietary modification, low level of Phe
6) Certain forms of the hyperphenylalaniemia do not cause mental retardation. What is the
reason for this?
Ch12 Molecular basis of genetic diseases 1/6

Because the moderate increase in phenylalanine in non-PKU hyperphenylalanemia is less
damaging to the brain.
7) Why is that certain forms of hyperphenylalaninemia do not respond to diet?
Due to requirement for the BH4 cofactor of two other enzymes,tyrosine hydroxylase and
tryptophan hydroxylase. Both of these are critical for synthesis of monoamine
nuerotransmitters.
8) How is diet-resistant PKU treated?
Try to normalize the neurotransmitters in the brains of these patients by administering the
products of tyrosine hydroxylase and tryptophan hydroxylase etc.
9) What can happen if fertile women homozygous for PKU do not continue the diet?
All her offspring becomes abnormal.
10) Describe the most important characteristics of storage diseases. Give an example.
Due to genetic defects of a variety of biological enzymes.
Tay–Sachs disease (also known as GM2 gangliosidosis or hexosaminidase A deficiency)

is a rare autosomal recessive genetic disorder. In its most common variant (known as
infantile Tay–Sachs disease), it causes a progressive deterioration of nerve cells and of
mental and physical abilities that commences around six months of age and usually
results in death by the age of four. The disease occurs when harmful quantities of cell
membrane components known as gangliosides accumulate in the brain's nerve cells,
eventually leading to the premature death of the cells. A ganglioside is a form of
sphingolipid, which makes Tay–Sachs disease a member of the sphingolipidoses. There
is no known cure or treatment.
11) What happened, when the fibroblasts of Hunter and Hurler syndrome patients were
cultures together? How do you call this phenomenon, and what is its significance?
Mucopolysaccharidosis type I (MPS IH; Hurler syndrome) is a congenital deficiency of

α-L-iduronidase, leading to lysosomal storage of glycosaminoglycans that is ultimately
fatal following an insidious onset after birth.
12) What is the importance of mannose-6 phosphate group in glycoproteins? Can the lack of
this group cause a disease? Explain.
They are essential for recognition of hydrolases by receptors on the cell and lysosomal
membrane surface.
I- cell disease, there is a defect in the enzyme that transfers a phosphate group to the
mannose residue. The fact that many enzymes are affected is consistent with the
diversity of clinical abnormalities seen in these patient.

13) Can you give an example of that not a missing enzyme, but an overactive enzyme is the
cause of a disease?
A certain enzyme, the CaM kinase II, keeps the cardiac muscle flexible. By transferring
phosphate groups to the giant protein titin, it relaxes the muscle cells. This is reported by
researchers led by Prof. Dr. Wolfgang Linke of the Institute of Physiology at the Ruhr
Universität in the journal Circulation Research. In failing hearts, which don't pump
enough blood around the body, the scientists found an overly active CaM kinase II. "The
phosphorylation of titin could be a new starting point for the treatment of heart failure"
Prof. Linke speculates.
14) Why are at risk the smoking alpha-1 antitrypsin deficient patients?
The patient's symptoms may resemble recurrent respiratory infections or asthma that
does not respond to treatment. Individuals with A1AD may develop emphysema during
their thirties or forties even without a history of significant smoking, though smoking
greatly increases the risk for emphysema.[1] A1AD also causes impaired liver function in
some patients and may lead to cirrhosis and liver failure (15%). It is a leading indication
for liver transplantation in newborns.
15) What do you mean by ecogenetics?
Specific hereditary susceptibility has now evolved into the field of ecogenetics. If you
have ever pondered why an individual is at greater risk for a specific disease, or sensitive
to a specific drug, then Gene–Environment Interactions is for you. Ecogenetics has
emerged in large part because of the advancements in technology and informatics in the
past 10 years. These technologies have provided a better understanding of the enormous
influence the environment has on gene expression.
16) What kinds of proteins can be affected in single-gene genetic disorders? Give at least 4
different kinds of proteins.
Receptor proteins, structural proteins, transport proteins, neuronal proteins.
17) What is the most frequent genetic cause for familial hypercholesterolemia, how is it
inherited, and what kind of cellular process is affected in the diseases?
Mutations in the gene encoding the LDL (low density lipoprotein) receptor. It is inherited
as an autosomal semi-dominant trait. Homozygous genotypes have severe deficits in the
number of LDL receptors and more plasma LDL cholesterol. Heterozygotes also have
higher levels of LDL cholesterol (2x as normal) but they are not as affected. Normal cells
uptake extracellular cholesterol bound to LDL. The uptake is mediated by the LDL
receptor found in clathrin-coated pits. It recognizes apoprotein B-100, the protein moiety
of LDL, binds to it, then the clathrin-coated pit endocytoses the LDL and cholesterol.
Mutation can inhibit any part of this process. For example, Class 1 mutations prevent the
synthesis of any detectable receptor. Other mutations involve the receptors not being able
to be transported to the Golgi complex, that is, protein folding is hindered (Class 2). Or
they can reach the cell surface but are unable to bind the LDL (Class 3). The mutation

may impair the localization of the receptor to the coated pit (Class 4), or also impair the
release of the receptor from the bound LDL (Class 5).
18) In the rarer forms of familial hypercholesterolemia which genes are altered by mutation?
Give at least 2 examples mentioning their biological function.
ARH adaptor protein, autosomal recessive inheritance. It is required for clustering the
LDL receptor in the clathrin coated pit. Loss of function mutation.
PCSK9 protease, autosomal dominant inheritance. When active, it degrades LDL
receptor. It prevents excess uptake of cholesterol. Missense mutation causes the disease.
19) What is the genetic cause of cystic fibrosis, how is it inherited? What kinds of tissues and
organs are affected?
The CFTR gene undergoes mutation, a deletion of phenylalanine residue at ΔF508. This
results in the loss of function of CFTR (CF transmembrane conductance regulator)
protein, which is involved in fluid and electrolyte transport across epithelial apical
membranes. It is autosomal recessive, so both parents must be carriers for the mutated
gene to be inherited. The lungs and exocrine pancreas are affected.
20) What is the genetic cause of Duchenne Muscular Dystrophy, how is it inherited? What
kind of cellular component is affected?
The deletion in the gene that codes for dystrophin (DMD gene), most of the time, the
whole gene (60%). Deletions are also often clustered in one of two regions within the
gene. The mechanism is unknown. Also, point mutations. DMD is X-linked and
recessive, so males are usually most severly affected. Dystrophin links the extracellular
matrix to the actin sytoskeleton. Without it muscle membrane integrity can not be
maintained, and proteins in the complex at the neuromuscular junction, for example, will
not function properly.
21) What do you mean by dynamic mutation? Name 2 diseases which are caused by this type
of mutation.
Dynamic mutation refers to expansion of repeated sequences within the transcribed

region of the affected gene. Huntington disease, Fragile X syndrome.
22) What do you mean by anticipation? What could be its molecular explanation?
Anticipation is the appearance of a disease at an earlier age at which it is normally

transmitted through a family. Its molecular explanation is slipped mispairing. In a gene
with lots of unstable repeats, an insertion occurs when the newly synthesized strand
suddenly dissociates from the template during replication. When the new strand and
template reassociate, the repeat sequence will align to a different place from where it is
supposed to and repeat copies will have slipped out.
23) Is it possible that a woman suffers from Duchenne Muscular Dystrophy? Explain!

Yes, but it is rare. Female DMD can be caused by nonrandom X-inactivation, Turner
syndrome with a mutation on the X-chromosome, or X;autosome translocation, and
rarely, heterozygous monozygotic twins.
24) What do you mean by dominant negative effect? Give an example.

Dominant negative effect means there is an altered gene product that impair the wild-type
allele’s functions. This usually results in an altered molecular fuction (inactive), and its
phenotype is dominant or semi-dominant. An example is mutations in p53, a gene whose
deactivation has a role in cancer.
25) How is the Fragile-X syndrome inherited? Who have the greatest risk for the disease?
By the inheritance of the maternal X-chromosome. The inheritance is dominant if one

copy of the altered gene in each cell is sufficient to cause the condition. Male children of
a permutation carrier have the highest risk for the disease.
26) Which are the most frequent genetic causes for mental retardation. Give at least 2.
The expansion of noncoding repeats that cause a loss of protein function (X-linked
fragile X syndrome)
Trisomy X (Down Syndrome)
27) Why do Down syndrome patients show the symptoms of Alzheimer disease?
A mutation in Beta-amyloid precursor protein gene leads to an increase of the product, A-beta
peptide, whose overproduction and accumulation causes Alzheimer’s, whether it be
monogenic or sporadic. Down syndrome patients have three copies of this BAPP gene on
chromosome 21, so there is a higher possibility of it being mutated.
28) How is it possible to diagnose Duchenne Muscular Dystrophy prenatally?
By screening for deletions and duplications by multiplex polymerase chain reaction.

Also, point mutations can be identified by sequencing the coding region and intron-exon
boundaries.
29) What proportion of Duchenne boys are born into families with no previous history of the
disease? What does this number tell us?
Approximately 80%. The disease is frequently caused by new mutations, and manifest in
only a minority of carrier females. DMD incidence will not decrease until a universal
prenatal screening for the disease is developed.
30) What are the main symptoms of Tay-Sachs disease, how is it inherited. What is the name
of the disease category it belongs to?
Infantile-onset Tay-Sachs: Progressive nerve cell deterioration, regression of motor
development usually around 6 months old, blindness, deafness, seizures, paralysis,
results in death by 2-4 years.
Juvenile onset Tay-Sachs: Rarer and between 2-10 years old. Cognitive and motor skill
deterioration, dysarthria, dysphagia, ataxia, spasticity. Death between 5-15 years
Adult-onset Tay-Sachs: Also rare. First symptoms during the 30s and 40sUnsteady gait,
progressive neurological deterioration, speech and swallowing difficulties, spasticity,
schizophrenia-like symptoms. Not as lethal.

It is autosomal-recessive, so both parents must be carriers to pass on the defective gene.
For those without a family history of Tay-Sachs, the risk depends on the frequency in
ethnic groups. In North Americans, 1/250. Ashkenazi Jews 1/30. Couples who are both
carriers, ¼.
Disease Category: Autosomal Recessive

1. What options do we have for the modification of the phenotype of a genetic disease?
Mention at least three of them.
Restriction of substrate uptake (diet in PKU),
Supplying the missing bioactive small molecule (thyroid hormone),
The use of alternative metabolic pathway to eliminate a toxic metabolite,
The use of metabolic inhibitors (inhibitors of cholesterol biosynthesis),
protein therapy (hemophilia A)
2. What is gene therapy? Describe the ex vivo approach.

To alleviate or overcome disease by the introduction of the wild type gene copy, or
replacement of the mutant gene with a functional gene copy
ex-vivo; to remove tissues or cells being alive from bodies or to utilize them
3. What kinds of vectors are used in gene therapy protocols? Mention at least 2 with short
characterization.
Retroviral vector
• Cannot be used for in vivo gene therapy, because the complement neutralize it.
• Can only infect dividing cells.
• Selectively infects cancer cells.
• Maximum cloning capacity is 8 kb.
Adenoviral vectors
• Is able to infect a wide variety of cells.
• Shows affinity to airway epithelium, cornea and intestinal epithelium.
• Enters the cell via receptor mediated endocytosis.
• Remains episomal.
• Can be used for in vivo gene therapy.
• Not selective for cancer cells.
• Disadvantage: its immunogenicity.
• Maximum cloning capacity is 35 kb.
Adeno-associated virus vectors
• Need helper virus to replicate.
• Integrates into a specific site on chromosome 19. (19q13.9-qter)
• There is no risk of insertional mutagenesis.
• A packaging cell line is required for its production.
• 96% of the virus genom was deleted (safety).
• Can accomodate inserts up to 4,5 kb
4. What do you mean by gene augmentation therapy?

In the case of loss-of-function (recessive) mutations introduction of the functional gene
copy may increase level of the normal gene product and alleviate or eliminate symptoms .
Ch13 Treatment of genetic diseases 1/7

5. What are the risks of random integrating vectors for gene therapy? Mention at least 2
factors.
a. Adenovirus vector can elicit an immune response, it can cause inflammation.
b. Insertional mutagenesis: The transferred gene will integrate into the patient’s DNA
and activate a proto-oncogene or disrupt a tumor-suppressor gene, leading possibly to
malignant neoplasia.
c. The illicit expression of an oncogene is less likely to occur with current viral vectors,
which have been altered to minimize the ability of their promoters to activate the
adjacent host genes.
d. Insertional inactivation of an essential gene can occur, but will, in general, be
without significant effect, because such lethal mutations are rare and will kill only
single cells.
6. What kind of recently developed methods are available to repair or inactivate a pathogenic
gene in a cell or in a tissue? Mention at least two of them.
Introduction of normal functional copies of a gene correct a reversible phenotype
Degradation of mutant RNA rather than removing the gene that encodes it
7. Which groups of human diseases are the most amenable for gene therapy protocols?
Mention at least 3 of them.
Severe combined immunodeficiency(SCID)
Haemophilia
Thalassemia
PKU
Urea cycle disorders
Familial hypercholesterolemia
8. One of the first well documented successes of gene therapy was the cure of X-linked
immune deficiency in the year of 2000. What kind of vector was used and what kind of
cells were targeted?
Retroviral vector
Bone marrow stem cells
9. In sickle cell disease and beta-thalassemia the increase of gamma-globin gene expression
can have a promising therapeutic effect. How is the increase of gamma-globin gene
expression achieved?
Histone deacetylase 9 activates expression increased γ-globin mRNA levels

10. If a dominant mutant gene product is toxic to the cell, the goal of the therapy is to
diminish the amount of the mutant protein made without disrupting the production of the
protein from the normal allele. RNAi can be used to degrade a specific target RNA, such
as that encoding the mutant huntingtin protein in Huntington disease.
11. Describe the two-hybrid system that makes use of the yeast GAL4 protein. What can you
detect with it?
Experiment in which yeasts are used to detect interaction within two proteins.
When you fuse each DNA-binding domain or transcription activating domain of
transcription factor such as GAL4 with protein of aim and manifest them within yeast
GAL4-depending gene expression will be induced.
12. Why are traditional therapies of genetic disease not very effective? List at least 3 reasons
for it.
(1) The gene causing the disease, or the pathophysiology of the disease is not known.
(2) The disease causes damage before it is diagnosed (e.g. in fetal stage).
(3) Severe cases are not responding as well as the milder forms. In the latter cases the
mutant proteins may have residual activity that could be increased.
13. Most of traditional therapies of genetic diseases interfere with metabolism. List at least 3
of these therapies, mentioning the name of the disease.
Dietary restriction;PKU
Replacement;congenital hypothyroidism
Diversion;urea cycle disorders
Inhibition;familial hypercholesterolemia
Depletion;hemochromatosis
14. In phenylketonuria the phenylalanine hydroxylase of substrate uptake is used to prevent .
15. The low phenylalanine diet is considered a dietary therapy.
16. In congenital hypothyroidism replacement of a small molecule is necessary. The name of

this molecule is thyroxine
17. diversion therapy is the enhanced use of alternative metabolic pathways to reduce the
concentration of a harmful metabolite.
18. In familial hypercholesterolemia two strategies are used to reduce plasma cholesterol
level. Briefly describe these two approaches.
I. By the diversion of an increased fraction of cholesterol to bile acid synthesis , the
single normal low density lipoprotein(LDL) receptor gene of these pateints can be
stimulated to produce more hepatic receptors for LDL-bound cholesterol
II. Pharmacological inhibition of enzymes is used to modify the metabolic
abnormalities of inborn errors.when the cholesterol load is decreased by diverting
it to other compounds or by removing it with physical methods.the lvier tries to

compensate for the decreased cholesterol intake by up-regulating cholesterol
syhnthesis
19. Treatment of hemophilia is considered a form of augmentation therapy.
20. Aminoglycoside antibiotics, such as gentamycin, encourage the translation apparatus to

skip over a premature stop codon and instead to misincorporate an amino acid. Whether
these effects can lead to clinical improvement without substantial toxicity remains to be
demonstrated.
21. Adenosine deaminase (ADA) deficiency is one cause of severe combined

immunodeficiency (SCID). The bovine ADA enzyme, covalently attached to polyethylene
glycol (PEG) was administered by infusion. This is considered an enzyme replacement
therapy.
22. Gaucher disease is the most prevalent lysosomal storage disorder. This autosomal
recessive condition is due to the deficiency of the enzyme glucocerebrosidase. The
principle of the treatment: carbohydrates of the glycoprotein are modified, terminal sugars
are removed to expose core α-mannosyl residues. The exposed mannose targets the
enzyme to the macrophage through a mannose receptor on the plasma membrane. In the
cell the mannose becomes phosphorylated , which targets the enzyme into the lysosome
23. What are the main characteristics of stem cells?

A cell that is capable both of generating another stem cell and of differentiating into
specialized cells within a tissue or an entire organism
24. Describe briefly the nuclear transplantation experiment. What is the medical significance
of this experiment?
Transfer of a diploid nucleus from an adult donor somatic cell into oocyte cytoplasm to
generate a cloned embryo.
Nuclear transplantation generate embryonic stem cells and they are genetically identical to
the donor nucleus.so they could be used for cell transplantation to the donor wthout fear of
immune rejection.
25. Bone marrow transplantation, in other words hematopoietic stem cell transplantation can
be used to treat genetic diseases. Which diseases are treated with this method? (List at
least 3.)
Lysosomal strorage disease
Beta-thalassemia
Gaucher disease
26. Briefly describe ex vivo approach of gene therapy.
Cells are removed from patients and modified within tubes and got back into patients
27. Describe the difference between germ line and somatic gene therapy. Which is currently
used in clinical trials?
Germ line gene therapy – banned in all countries
– Genetic modification of human gametes, zygotes or the early embryo.
Somatic cell gene therapy

– Genetic modification of somatic cells and tissues of the patient.
– Not inherited
– Requires permission
28. Describe gene augmentation therapy.

A procedure for correcting metabolic deficiencies caused by a missing or defective gene
by having a healthy gene produce the necessary product without actually substituting that
gene for the flawed or absent gene in the DNA.
29. How can gain-of-function mutations be corrected by gene therapy?
Gene reprogramming is based on inhibition of the expression of the mutated gene by
modification of messenger RNA (mRNA) and is applied to disorders of gain-of-function
mutations
30. What are the essential requirements of gene therapy for a genetic disease? List at least 4 of
them.
Identity of the molecular defect
A functional copy of the gene
Knowledge of the pathophysiological mechanism
Favourable risk-to-benefit ratio
Appropriate regulatory components for the transferred gene
An appropriate target cell
Strong evidence of efficacy and safety
Regulatory approval
31. What are the possible target cells of gene therapy? List at least 3 of them.
Stem cells
Progenitor cells
Endothelial cells
32. Which vectors are the most widely used classes of viral vectors for gene therapy? List at
least 3 of them.
1. retroviruses
2. adenoviruses
3. adeno-associated viruses
33. What is the purpose of the use of a packaging cell (vector producing cell)?
The genes necessary for viral particle production and packaging were replaced by
therapeutic genes in viral vectors,so they need a cell containing those genes for the
packaging of the vector genome into viral particles
34. What kinds of non-viral ways of gene transfer do you know? Mention at least 3 of them.
DNA packaged in liposomes
Protein DNA conjugates
Artificial chromosome
Naked DNA
35. What are the risks of gene therapy? Mention at least 3 of them.
Adverse response to the vector(patient have an adverse reaction to the vector or the
transferred gene)

Insertional mutagenesis causing malignant neoplasia(transferredgene will integrate into
the patient`s DNA and activate a proto-oncogene or disrupt a tumor-suppressor gene,
leading to malignant tumor)
Inserional inactivation of an essential gene(insertion al inactivation could disrupt a gene
essential for viability)
36. Demonstrate the promises and the risks of the gene therapy using the gene therapy of
Severe Combined Immunodeficiency in the year of 2000, as an example.
Retroviral vector-transduced cells were injected into patients.because there are stem cells
in bone marrow,gene expression were stable. you get genetype of patient and also
phenotype. you can have selective survival advantage
Genome was introduced into patients and it can be possible to disrupt genome of patients.
some of them has leukemia-like disorder
37. Describe gene therapy of Adenosine Deaminase (ADA) deficiency. What kind of target
cells and what kind of vector were used?
Bone marrow stem cells are transduced ex vivo with a retroviral vector expressing an
ADA cDNA.the transduced cells are transplanted into the patients whose bone marrow has
been partially ablated to improve engrafment of the gene-modified marrow
38. How was hemophilia B treated with gene therapy?
Intravenous replacement of the deficient factor
39. How can an antisense oligonucleotide be used for the gene therapy of Duchenne Muscular
Dystrophy? Explain the principle.
Antisense oligonucleotides (AOs) targeted to splicing elements within DMD pre-mRNA
can induce the skipping of targeted exons, restoring the ORF and the consequent
production of a shorter but functional dystrophin protein. This approach may lead to an
effective disease modifying treatment for DMD and progress towards clinical application
has been rapid
40. There is a recently developed method to insert genes, or to inactivate undesirable genes in
the genome. It uses sequence specific DNA-binding domains coupled to an endonuclease.
It is called Zn-finger nuclease
41. Write 3 examples for gene therapy approaches used in cancer.

Direct killing of disease cells;artificial cell killing involves transfer to cells of genes
encoding toxic compounds or prodrugs
Assisted killing of disease cells by immune system cells;gene of foreign MHC antigen is
introduced which evokes an immune response-cytokine,TNF,interferon encoding gene is
introduced.tese gene products have an anti-tumor effect
Targeted inhibition ;inhibition of unwanted responses in autoimmune diseases
42. Artificial cell killing involves transfer of genes encoding toxic compounds (suicide genes)
or prodrugs (reagents which confer sensitivity to subsequent treatment with a drug) into
cells. In gene therapy of a brain tumor glioblastoma multiforme thymidine kinase is the
prodrug gene introduced into the tumor using a retrovirus vector and gancyclovir is the
drug injected intravenously. Explain why is this treatment causing selective killing of the
tumor cells and not affecting normal cells?
Because these genes are only injected into tumor cess but not into normal cells

43. How can you achieve targeted inhibition of gene expression? Write at least 3 examples.
Such as Antisense oligonucleotide,siRNA or ribozyme are joined into disease cells
containing mutant or harmful gene.that block expression of pathogenic gene
44. How can you manipulate oncogene and tumor suppressor gene expression in gene therapy
treatment of cancer? Give the principles and mention at least one concrete example.
Oncogene can be inactivated by targeted inhibition of gene expression
Tumor suppressor gene can be introduced into the cells with the help of vector
Retrovirus . adenovirus.p53.BRCA1.cDNA

1. The fertilized egg, also called the _zygote_, has the capacity to give rise to every cell in
the adult body; it is therefore said to be _totipotent_.
2. Products of _morphogen_ genes help establish the axes of the developing embryo
according to their concentration gradient.
3. _homorogous_ organs evolved from a structure present in a common ancestor.
4. _analogous_ organs appear similar but arose independently from one another.
5. Please explain what morphogens are! Please mention at least one example too.
(definition of morphogen)
Morphogen is a substance produced by cells in a particular region of an embryo that diffuse
from its point of origin through the tissues of the embryo to form a concentration gradient.
Cells undergo specification and then determination to different fates, developing on the
concentration of morphogen they experience.
(example)
Bicord and sonic hedge hog
6. What are the two classes of mutations that are useful to analyze the genetic regulation of
differentiation? Please explain the major characteristics of these types of mutations.
Maternal-effect genes and zygotic genes mutation.
These mutations that affect oocyte composition or structure can upset development of the
embryo.
7. Hox genes that encode transcription factors, all have a 180 base pair sequence known as
the _homeobox_, which encodes a 60–amino-acid sequence known as the _homeodomein
(helix turn helix)_.
8. Explain the concept of pleiotropy through a human example.
One gene can affect more than one trait through secondary or indirect effects. The various,
sometimes seemingly unrelated effects of a mutant gene are called pleiotropic effects, and
the phenomenon itself is known as pleiotropy.
A classic example of pleiotropy is the human disease PKU (phenylketonuria). This disease
can cause mental retardation and reduced hair and skin pigmentation, and can be caused
by any of a large number of mutations in a single gene that codes for the enzyme
(phenylalanine hydroxylase), which converts the amino acid phenylalanine to tyrosine,
another amino acid. Depending on the mutation involved, this results in reduced or zero
conversion of phenylalanine to tyrosine, and phenylalanine concentrations increase to
toxic levels, causing damage at several locations in the body. PKU is totally benign if a
diet free from phenylalanine is maintained.
Ch14 Developmental genetics 1/4

9._maternal effect_ are environmental effects (e.g. drugs) that may cause a wide variety of
birth defect.
9. What is the key difference between specification and determination in the development of
differentiated cells?
Specification is reversible, determination is not.
10. If cellular development does not involve permanent changes in DNA (except for DNA
rearrangement in lymphocyte precursors), how can you explain obvious differences
between various mature cell types (e.g. a neuron and a liver cell)?
Cell differenciation is due to gene expression.
11. Stem cells are _ pluripotent_ , meaning that they can differentiate into a number of various
cells types, but not any cell of the organism.
12. Why do we distinguish between maternal effect and zygotic genes in development?
While maternal-effect genes are genes that function in the mother that are needed for
development of the embryo, zygotic genes are developmental genes that function in the
embryo. The correlation between them is that the zygotic genes interpret and respond to
the positional information laid out in the egg by the maternal-effect genes.
13. Genes that function in the mother that are needed for development of the embryo are
called _coordinate (maternal effect) _ genes.
14. Describe “gain of function” mutations.
Dominant mutation genes product acquired gaining new activity or over expression
15. Define and describe the term “homeobox”.
The homeotic genes are transcriptional activators of other genes. Most HOX genes contain
one or more copies of a characteristic sequence of about 180 nucleotides called homeobox,
which is also found in key genes concerned with the development of embryonic
segmentation in organisms as diverse as segmented worms frogs chickens, mice, and
human beings. Homeobox sequences are present in exons and code for a protein-folding
domain that includes a helix-turn helix DNA-binding motif.
16. Mutations in _homeotic_ genes result in replacement of one body part or segment by
another.
17. What are the two principal mechanisms that restrict the developmental potentials of cells
during development?

Autonomous(genetically programmed changes within cells themselves) and positional
information imposed by position of cells within the embryo.
18. What is the consequence of mutations in homeotic genes?
Homeotic mutations results in the transformation of one body segment into another, which
is recognized by the misplaced development of structures that are normally present
elsewhere in the embryo.
19. .A cell that is capable of differentiating into a complete organism is called a _totipotent
stem_ cell.
20. Genetically programmed cell death is known as _apotosis_.
21. Genes that function in the mother that are needed for development of the embryo are
called _maternal-effect (coordinate)_ genes.
22. Mutations in _maternal-effect (coordinate)_ genes are easy to identify because

homozygous females produce eggs that are unable to support normal embryonic
development, whereas homozygous males produce normal sperm.
23. What type of genes has homeoboxes? How is the homeobox important to the function of
the protein?
(type of genes)
Homeotic genes
Homeotic genes are defined by a DNA sequence known as the homeobox, a sequence of
180 nucleotides that codes for a protein domein known as the homeodamein is part of the
protein that attaches to specific regulatory region of the target genes.
24. Suppose that M is an autosomal maternal effect gene, and its recessive mutation results in
a non-functioning protein. What progeny do you expect in the F1 generation if you cross a
MM male to a Mm female? What would be the result of the reciprocal cross?
If the mother is heterozygous and the mutation is recessive, no mutation would occur
since the maternal effect genes only come from the mother.
24. Supposing that Z is an autosomal zygotic gene controlling embryonic development, and
its recessive allele z encodes a non-functioning protein, what genotypic ratio do you
expect in the surviving members of the F1 generation from a Zz X Zz cross?
50 % will have non-functioning protein genotype zz.

25. Describe the role of nurse cells in the development of the embryo.
Nurse cells are specialized macrophages residing in the bone marrow that assist in the
development of red blood cells. They absorb the nuclei of immature red blood cells and
may provide growth factors to help the red blood cells mature. In the bone marrow,
immature red blood cells (erythroblasts) can be seen grouped in a cluster around a nurse
cell.
26. What is the role of homeotic genes in development?
The role of homeotic genes is to transform the periodicity of embryo into a body plan with
linear differentiation.
27. Synpolydactyly is a condition caused by a mutation in a _HOXD13_ gene.
28. Holoprosencephaly is a failure in forebrain development caused by the defect of _SHH

genes_.
29. What are gain-of-function and loss-of-function mutations in developmental genes? How
are they inherited?
Protooncogene may suffer dominant gain of function mutations, and tumor suppressor
may suffer loss of function mutations in heterozygote, ressesive.
It’s higher possibility that they are inherited to have loss of function than to have gain of
function because loss of function mutation can cause cancer not in homozygote but in
heterozygote, that means it has balance carrier to inherit to next generation.
30. Please give a definition of the term “morphogenesis”.
Morphogen is a substance produced by cells in a particular region of an embryo that

diffuse from its point of origin through the tissues of the embryo to form a concentration
gradient. Cells undergo specification and then determination to different fates, developing
on the concentration of morphogen they experience.

1 Name and define two invasive prenatal testings!
Amniocentesis ; a procedure used in prenatal diagnosis to obtain amniotic fluid, which

contains cells of fatal origin that can be cultures for analysis. Amniotic fluid is
withdrawn from the amniotic sac by syringe after insertion of hollow needle into the
amnion through the abdominal wall and uterine wall. [glossary]
Chorionic villus sampling (CVS) ; it involves the biopsy of tissue from the villous area
of the chorion transcerviocally or transabdominaly, generally between 10th and 12th
weeks of pregnancy[p446]
Cordocentesis ; a procedure used in prenatal diagnosis to obtain a sample of fatal

blood directly from the placenta [glossary ]
Preomplantation genetic diagnosis ;

（教科書に CVS と amniocentesis だけ詳しい説明があるので、その２つをテストで書いた方が良いと思います。）
2 How can neural tube defects be prevented?
Periconceptional supplementation with folic acid (i.e., at least 1 month before

conception and continuing through the first trimester of pregnancy) has been shown
to decrease the incidence of NTDs by nearly 75%. A 40% reduction in the incidence
of orofacial clefting has also been demonstrated with periconceptional folic acid
supplementation.[slide]
3 Name and define at least two noninvasive prenatal testings!
Maternal serum alpha-fetopotein(MSAFP) ;measured in second trimester as a

sccreening for NTDs
First trimester maternal serum screening ；it is ideally performed between week 11
and week 13 of gestation. It relies on 1) quantifying the levels of certain substances in
maternal serum and 2) measuring substance of the lateral by a highly targeted
ultorasonographic examination. Maternal serum substances are pregnancy-
associated plasma protein A(PAPP-A) and the hormone human chorionic
gonadotropin (hCG). PAPP-A is depressed below the normal range in all trisomies
and hCG is elevated in trisomy 21 but depressed the other trisomy.
Second trimester maternal serum screening ; measuring three substances in the

mother’s serum(MSAFP,free beta-hCG, and unconjugated estriol.) all of these
substances are depressed below the normal range in all trisomies
Ch 15 & 17 & 19 & 20 1/6

(inhibin A is also measured. It is elevated in trisomy21 but not significantly affected in
the other trisomies.)
Ultrasonography ;a technique in which high frequency sound waves are used to

examine internal body structure.(for detecting down syndrome and NTDs…)
Isolation of fetal cells from maternal circulation.
4 In what case can it be medically important to determine the fetal sex?
Ultrasound examination can be used from 15 weeks of gestation onward to

determine fetal sex. This determination may be an important prelude or adjunct in
the prenatal diagnosis of certain X-linked recessive disorders (e.g., hemophilia)
for those women identified to be at increased risk. A couple may decide not to
proceed with invasive testing if a female (and therefore likely unaffected) fetus is
identified by ultrasound examination.
5 Explain how screening for phenylketonuria is possible? Why is it critically important

to obtain an early diagnosis for PKU?
Mental retardation associated w/ PKU can be prevented if dietary restrictions are

applied immediately after birth, i.e. accumulation of phenylalalnine is prevented.
6 For what abnormalities can FISH be used for rapid aneuploidy testing?
Screen interphase nuclei for common aneuploidy of chromosomes 13, 18, 21, X
and Y immediately after CVS or amniocentesis.
7 What does „multiplex testing” mean (e.g. for mutations causing cystic fibrosis)?
The technology for detecting many different mutant alleles in a gene simultaneously
in a single procedure [slide]
8 What is preimplantation genetic diagnosis?
It is the use of molecular or cytogenetic techniques during in vitro fertilization to

select embryos free of a specific genetic condition for transfer to the uterus.
(It cans be performed by micromanipulation techniques to remove a polar body or by

biopsy of single cell from a six to eight cell embryo after fertilization )[p456]
9 For what genetic conditions can family history help the most in calculating the risk for
a disease?
Ch 15 & 17 & 19 & 20 2/6

Assessment of complex disorders; share genes and environment. Risk evaluated
based on number of relatives affected by it and degree of relation between relative
and subject; high risk, moderate risk and avg. risk (no affected relatives).
10 What is called a disease association?
The presence or decrease s frequency in affected individuals compared with control is

know as a disease association.[p.224]
11 In what ways is it possible to evaluate how appropriate a genetic screening test is for
predicting the genetic susceptibility for a disease?
Screening at the population level is not to be confused with testing for affected
persons or carriers within families already identified because of family history.
Rather, the objective of population screening is to examine all members of a
designated population, regardless of family history.
12 Name two genetic diseases for which a successful newborn screening has been
applied!
Phenylketonuria, congenital deafness and congenital hypothiroidism.
13 List the three strategies used in Genetic epidemiology studies! Which one provides the
most complete information?
• Case-control: Individuals with and without the disease are selected, and the
genotypes and environmental exposures of individuals in the two groups are
determined and compared.
• Cross-sectional: A random sample of the population is selected and divided into

those with and without the disease, and their genotypes and environmental
exposures are determined and compared.
• Cohort: A sample of the population is selected and observed for some time to
ascertain who does or does not develop disease, and their genotypes and
environmental exposures are determined and compared. The cohort may be selected
at random or may be targeted to individuals who share a genotype or an
environmental exposure.
Ch 15 & 17 & 19 & 20 3/6

→ randomly selected cohort study is the most accurate and complete
Because …
Cross-sectional studies suffer from underestimation of the frequency of the disease
(if the disease is rapidly fatal, or the disease shows age-dependent penetrance)
Case-control studies allow researchers to efficiently target individuals, particularly

with relatively rare phenotypes that would require very large sample sizes in a cross-
sectional or cohort study.
Usually does not capture information on the population prevalence of the disease.
（Genetic epidemiology is concerned with how geno-types and environmental

factors interact to increase or decrease susceptibility to disease. Epidemiological
studies generally follow one of three different strategies）
14 Name a disease for which genetic susceptibility testing of asymptomatic individuals

can be applied with some clinical benefits!
Testing asymptomatic people raises several questions: Does the test provide
additive prognostic information to that obtained from traditional risk factors? Is the
use of the test associated with improved outcomes? Is the test cost-effective?
Other points include unnecessary use in lower-risk persons, and what has been
called the "slippery slope to invasive testing," where findings on one test lead to
more testing. Disease that shows clinical benefits for asymptomatic testing is e.g.
Medium Chain acyl CoA dehydrogenase (MCAD) deficiency, a disorder of fatty
acid oxidation that usually is asymptomatic but manifests clinically when patient
becomes catabolic and can cause death with first episode of hypoglycemia.
15 For what diseases could carrier (heterozygote) screening decrease the disease
incidence?
severe autosomal recessive or X-linked illness.
16 What kind of laboratory tests provide the basis of genetic counseling? (List three
kinds!)
Karyotyping, biochemical analysis and DNA analysis.
17 In what case can donated egg and artificial insemination (together) be a solution for
substantially increasing the chance of having a healthy kid?
Preimplantation genetic diagnosis, selecting the genetically fittest embryos for

implantation.
Ch 15 & 17 & 19 & 20 4/6

18 How do we call the method that is used in pedigree analysis (for genetic counseling),
when alternative genotypes are possible?
Bayesian method/analysis.
19 For what type of diseases (with strong genetic component) is ’empirical recurrence
risk’ determination applicable?
Cleft lip and palate, eongenital heart disease, meningomyelocele, psychiatric illness,
and coronary artery disease.[519]
20 List four cardinal ethical principles that should be followed in medicine?
- respect for individual autonomy

- beneficence (doing good for the patient),
- avoidance of maleficence (primum non nocere: "first of all, do no harm"), and
- justice (ensuring that all individuals are treated equally and fairly).
（Complex ethical issues arise when these principles are perceived to be in conflict
with one another. There is a need to weigh and balance conflicting demands）
21 In what situation ’duty to warn’ arises for a medical practitioner?
When the patient’s insistence that his or her medical information be kept strictly
private restrains the geneticist from learning other family members known about their
risk for a condition, even when such information could be beneficial to them with
regard to their own health and the health of their children .
The genetic practitioner strictly obligated to respect the patient’s autonomy by keeping
information other family member (duty to warn)[p525]
22 What is eugenics?
Increasing prevalence of desirable traits in population by decreasing the frequency of

deleterious alleles at relevant loci through controlled, selective breeding. The opposite
is dysgenics.[p528]
23 Why is it expected that a eugenic program fails for complex traits?
Most human traits are complex in their inheritance pattern and are strongly
influenced by environmental factors.
24 What does ’dysgenics’ mean?
Ch 15 & 17 & 19 & 20 5/6

It is a determination in health and well-being of a population by practices that allow
the accumulation of deleterious alleled.
Ch 15 & 17 & 19 & 20 6/6

1. Cancer cells are characterized by __uncontrolled proliferation__.
2. What is the consequence of a loss of function mutation in p53 gene?

If there is no functional copy of TP53, then there is no DNA damage checkpoint, DNA
damages are not corrected (mutations), or apoptosis cannot be induced because of DNA
damage.
3. A key protein in the mammalian cell's response to stress in general, and to DNA damage
in particular, is a protein called the ______p53______.
4. Mutations in oncogenes are __Gain of function (GOF)__ mutations because they

improperly enhance cell proliferation or inhibit apoptosis.
5. ___Tumor-suppressor__ genes are genes that normally control cell proliferation or that
activate the apoptotic pathway, in which loss-of-function mutations contribute to cancer
progression.
6. When internal and external conditions are inappropriate to initiate a division cycle, the
cells accumulate at the G1 restriction point. In animals, what protein is responsible for
keeping cells at this restriction point?
Rb (retinoblastoma protein). Its unphosphorylated form is attached to E2F transcription
factor preventing its transcriptional activator effect on genes necessary for DNA synthesis
and entering S phase.
7. In familial retinoblastoma, are always mutations in the normal RB1 gene responsible for
the loss of heterozygosity?
Not necessarily, the normal allele can be mutated or can be lost by deletion of the gene or
the chromosome, or it can be converted to the mutant allele because of gene conversion,
the regulatory sequences (promoter, enhancers) can be lost or mutated, or the normal allele
can be inactivated by heterochromatisation. It is possible, that oncogene activation down
regulates the expression of the normal allele.
8. What would be the expected result of a nonsense mutation in BRCA2 gene?

BCRA2 is involved in double-strand break repair and/or homologous recombination
(gatekeeper). Nonsense mutation creates a STOP codon from an amino acid coding codon,
which causes early termination of translation and result in a nonfunctional protein, or no
protein is produced at all. The mutation is dominant, if there is a mutant allele, cancer can
appear (breast cancer, ovarian cancer, pancreatic cancer, Fanconi anemia,…)
9. What is the major difference between hereditary cancer syndrome and sporadic cancer
cases?
In case of hereditary cancer syndrome initial cancer-causing mutation is inherited through
the germ lines while sporadic cancer is caused by somatic mutations.
10. What are oncogenes? Please give an example and explain its function!
Oncogenes are dominantly acting genes (gain of function mutation of original proto-
oncogenes involved in cell division or proliferation) responsible for tumor formation.
Mutation, overexpression or amplification of oncogenes in somatic cells may lead to
neoplastic transformation (tumor formation).
Ch16 Cancer genetics 1/2

11. What are tumor suppressor genes? Please give an example and explain its function!
A normal gene involved in negative regulation of cell proliferation (or trigger apoptosis)
in which recessive loss of function (LOF) mutations can lead to tumor formation. E.g. Rb,
see Q6.
12. Tumor-suppressor genes are divided into two groups. What kind of genes belongs to the
gatekeeper group and what is their normal function?
Directly suppress tumor formation by negative regulation of cell proliferation or by
triggering apoptosis. Eg. p53, Rb, p21
13. Tumor-suppressor genes are divided into two groups. What kind of genes belongs to the
caretaker group and what is their normal function?
Usually they are involved in DNA repair and genome maintenance. E.g. BRCA1, BRCA2,
14. What is loss of heterozygosity? What kind of mechanisms could be responsible for this
phenomenon?
Loss of heterozygosity (LOH) is a phenomenon when somebody has heterozygous
genotype, and in one of his/her cells the normal allele is lost, cannot be expressed or
becomes mutated. It is a typical mutation of tumor suppressor genes found in hereditary
(familial) cancers. The normal allele can be lost because of deletion of the gene or loss of
the chromosome, it is possible, that the chromosome is lost and the mutant allele
containing chromosome is duplicated; the normal allele can be mutated because of point
mutation, insertion, inversion, frame-shift mutation (“local events”), or somatic (mitotic)
recombination and gene conversion (it is a form of genetic recombination, in which one
version of a gene (allele) is observed to replace a different version; at the level of DNA a
duplicate copy of the donor allele appears in the recipient DNA, while the recipient allele
is lost). Loss of the promoter or other regulatory sequences (enhancers), down regulation
of the expression of the normal allele, or the heterochromatisation of the gene can also
eliminate the function of the normal allele.
15. What is the Philadelphia chromosome? How is it generated and why is it deleterious for
the cells?
The Philadelphia chromosome, t(9;22)(q34;q11): translocation between chr.9 and chr.22.
in chronic myelogenous leukemia (CML).
The ABL gene (ch.9q) is fused to the BCR gene on ch.22q. The result is a constitutively
active tyrosine kinase.
16. What is loss of heterozygosity and how is this phenomenon related to the progression of
some type of cancers?
Loss of heterozygosity (LOH) is a phenomenon when somebody has heterozygous
genotype, and in one of his/her cells the normal allele is lost, cannot be expressed or
becomes mutated. It is a typical mutation of tumor suppressor genes found in hereditary
(familial) cancers. Both alleles of a tumor-supressor gene have to be inactivated by
mutations or epigenetic effects (two-hit origin of cancer), and when somebody is born
with a mutant allele (has heterozygous genotype for the tumor-suppressor) only one
mutation is necessary in one somatic cell for the development of a cancer (not two
mutations like in a homozygous dominant individual), so the probability that a
heterozygous person will have a cancer is very high (in case of retinoblastoma – Rb1 gene
mutation – it is 100% in an early childhood).
Ch16 Cancer genetics 2/2

1. Give examples of metabolic modifications of drugs which are effected by genetically
determined proteins.
Phase1 reactions: hydrolysis,reduction,oxidation.hydroxylation

Phase2 reactions: glucuronidation.sulphonation. acetylation,methylation:conjugation with
glutathione or amino acid.
2. What is the most important enzyme system in the metabolism of drugs? Give at least 3
characters of these enzymes.
CYP enzyme
 SER in liver cells
 highly Polymorphic
 Have families
 by excretion in bile or urine
Hepatic enzyme are responsible for the metabolism of drug by activating them and then
conjugating the active secondary metabolite with glucoronic or sulphuric acid, or glutathione,
followed by excretion in bile or urine.
3. What is the most important difference between the P-450 group of enzymes and the
commonly known metabolic enzymes?
commonly known metabolic enzymes:

if there is mutation, it is visible
P-450 group of enzymes:
Not visible(cannot see phenotype)
Detected by administration of taking the drug
4. What is the most important organ in drug metabolism? Why?
Liver.
SER ⇒CYPenzyme located⇒drug metabolism
Predominantly located in the smooth endoplasmic reticulum(SER; they are mentioned also as
microsomal enzymes)of liver cells(hepatocytes),but also can be ascertained in some other
organs(intestinal epithelium and so on).
5. A drug can be a ................... of a CYP enzyme while it is an inhibitor of another …..

..................
Substrate
CYP ensyme
6. There are some people who are slow acetilators of the drug INH. Being treated with that
drug do they require regular, higher or lower doses of INH? Explain.
Lower, their sensitivity of drug is enhanced.
Ch18 Pharmacogenetics 1/6

7. Give an example of drug teratogenicity.
Contergan (right picture)

An mild sedative (used to combat nausea in
pregnant women in early phase of
pregnancy)which caused severe thalidomide
embryopathies, e.g phocomelia
8. Succinyl cholin turned out to be very

dangerous (even lethal) to people with a
given genotype. What is that genotype?
Atypical allele
• The drug Suxamethonium (or succinylcholine) has been commonly used as a muscular
relaxant for intubation anesthesia. It stops breathing, too, but it is hydrolyzed by the
butyrylcholinesterase enzyme (encoded by the Usual allele of BCHE) within 1-3
minutes and spontaneous breathing recovers.
• In some persons the enzyme (encoded by the Atypical allele) has a poor affinity for
the drug, and such patients develop a prolonged apnea due to repression of respiratory
muscles. Under such circumstances many hours of machine forced respiration may be
necessary (with the tracheal tube in position).
• This trait is an autosomal recessive defect. The frequency of homozygous recessive
persons is about 1 in 2,000.
9. Are drugs xenobiotics to the human body or not? Explain.
Yes
Xenobiotic is organic chemical which is taken up and found in an organism but which is not
normally produced or expected to be present in it, or which are present in much higher
concentration in the [human]body than usual.
10. Is it possible that one of our CYP enzymes can transform a chemical in our body to a
carcinogen? Explain.
Yes
Benzopyrene (Procarcinogen) is turned to be benzopyrenediolepoxide(carcinogen) by CYP.
90% mutagen material are carcinogen
Because CYP is mutagenic material.
11. Is it possible that environmental xenobiotics can interfere with drug metabolism? Explain.
Yes
Strong link is seen between pharmacogenetics and ecogenetics.
Hemolytic shock in G6PD deficient persons can be evoled by drugs and by some natural
compounds present in our environment (favism caused by ingestion of fava beans, breathing
in pollens and some other causes.)

12. Do plants and/or animals modify xenobiotics appearing in their environment or in their
food? What is the impact of that possibility on human medicine?
Food additives fall practically in the same category as drugs.

Chemicals used in industry and first of all in agriculture(pestisides,artificial fertilizers and
so on )which are absorbed by the plants and accumulated …(see detail in lecture slide48)
Chemical->plant->animal product(milk,meat)->human
13. May actual diet modify the effect of drugs? Explain.
Dietary habits,preferences
 Smoking,alcoholic beverages
 Grapefruit=an enzyme inhibitor
 Cabbage,broccoli,nicotine,ethyl alcohol, and so on=enzyme inducers
 Vitamin K supply during warfarin treatment
14. Is it possible that administration of a given drug may modify the effect of another drug?
Explain.
Drug can be activator or inhibitor of CYP enzyme.

Because of modified activity of CYPenzyme can affect modification of other drug.
15. What is the role of the cytochrome P-450 enzyme family in medicine?
Drug elimination by the enzymes that catalyze the oxidation of organic substances.
Sometimes modification of CYP enzyme is necessary for activiation of enzyme.
e.g. terfenadine(question 30)
http://en.wikipedia.org/wiki/Cytochrome_P450
16. Is it possible that genotype analysis determines the pharmacotherapy of a given illness?
Yes
People with a particular version of a CYP enzyme suffered serious adverse effects when they
took Seldane (or Terfenadine) with the antibiotic Erythromycin.
A study in The Lancet found that a drug given to 400 Alzheimer’s patient had no statistically
significant effect, but when patients were stratified according to their Apo E subtype,
investigators detected a clinically significant response. Thus, genetic stratification of a
population can be the difference between drug failure and drug approval.
17. Can you show a link between pharmacogenetics and ecogenetics? Which is a good
example?
Yes
Haemolytic shock in G6PD deficient persons can be evoled

By drugs
By some natural compounds present in our environment
18. Vicia fava. Which defect sensitizes a kind of individuals to that bean? Whom?
Vicia fava(ソラマメ)
Raw broad beans contain the alkaloids vicine, isouramil and covicine, which can induce
hemolytic anemia in patients with the hereditary condition glucose-6-phosphate
dehydrogenase deficiency.
19. Someone is an ultrafast metabolizer of a drug. Does that person need higher or lower
doses of that very medicine? Explain.
higher
their drug level in plasma is low with time,faster than nomal people and doses might be
inadequate to maintain blood levels in the therapic range.
20. Do animals possess a kind a cytochrome P-450 enzyme family? Explain.
Many animals have as many or more CYP genes than humans do. or example, mice have
genes for 101 CYPs, and sea urchins have even more (perhaps as many as 120 genes)
21. Do animal cytochrome P-450 enzymes affect molecules important in human nutrition?
Yes, they do.

When it is xenobiotic for animals.
22. At which sites (locations) of metabolism can CYP enzymes exert their effect on drugs?
In phase1
Predominantly located in the smooth endoplasmic reticulum of liver cells, but also can be
ascertained in some other organs. And intestinal epithelium is also.

23. CYP enzymes are considered as principal players in drug metabolism. Which other
proteins are also important in that aspect?
p-glycoprotein
participates in the transport of the drug.
Enzyme involved in phase 2 reactions: glucuronidation, sulphonation, acetylation,
methylation; conjugation with glutathione or amino acids.
24. What is that regular anatomical way of drugs along which CYP enzymes exert their
effects?
http://en.wikipedia.org/wiki/Drug_metabolism
intake->absorption in intestine->distribution in blood->drug-cell interaction->breakdown in
liver or in intestinal cells->eccretion into bile and urine
25. What is very typical characteristic of genetic determination to CYP enzymes?
Typically have a number of allelic variants, i.e. their polymorphism in the population is
high.
Besides allelic variants there are a number of isoforms based on alternative splicing of the
primary transcript and/or alternative promoters of the genes concerned.
26. What proteins are important in drug metabolism and realization of drug effects other than
CYP enzymes?
Enzymes which are involved into phase 2 reaction: glucuronidation, sulphonation, acetylation,
methylation; conjugation with glutathione or amino acids
27. Define the term xenobiotic.
Xenobiotic is organic chemical which is taken up and found in an organism but which is not
normally produced or expected to be present in it, or which are present in much higher
concentration in the [human]body than usual.

28. List minimum three xenobiotics.
 Drugs
 Pollutants such as dioxins and polychlorinated biphenyls
 Natural compounds if they are taken up by another organism
29. Are drugs xenobiotics? Explain.
yes
see definition in question 27
30. Some CYP enzymes inactivate given drugs. What can be the opposite function of a CYP
enzyme?
This case can be seen in terfenadine.

Though the drug molecule as administered,was ineffective,it’s converted into terfenedine
carboxylate by CYP3 4A in the liver. This comound is no-sedating antihistamine medicine.

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1) In human at the end of meiosis I how many chromosomes and how many chromatids are

present per cell? 23 46

6) What does semiconservative replication mean?

7) Describe the Hershey-Chase experiment. What was demonstrated by the experiment?

21) The pairing of homologous chromosomes during meiosis is known as

4) Why is it important that excision of introns be precise to the level of a single

9) ___RNA polymerase__3___________ transcribes all tRNA genes and the 5S component

10) RNA polymerase _______2___________ is responsible for transcribing all protein-

11) In eukaryotes, RNA polymerase _________1_________ is used exclusively in producing

16) In eukaryotes, transcription and RNA processing takes place in the

21) Many eukaryotic genes are _______housekeeping______________ genes that encode

40) Compare eukaryotic and prokaryotic ribosomes with respect to

43) Describe the most important events of translation initiation in eukaryotes.

48) Is it possible to translate an mRNA in a bacterial cell if it lacks the Shine-Dalgarno

57) .……aminoacyl………………….. ……tRNA…… …synthatases…………binds the

58) ……wobble…………………….is the name of the special feature of codon-anticodon

2) What is the role of colchicine in chromosome investigations? It is a mitosis- inhibition

3) What is the role of phytohemagglutinin in chromosome investigations? Induce mitosis

4) Define the term: haploid. Only single set of chromosome.

5) Define the term: diploid. Two sets of chromosome.

6) Which human cells are haploid? Gametes.

8) What is the chromosome number of a human gamete? 23

9) How many chromosomes are in a human zygote? 46

14) What is karyogram? A diagram or photograph of the chromosomes of a cell, arranged in

15) What is a karyotype? the chromosomes of a cell, usually displayed as a systematized

19) Name a monosomy syndrome in humans. Turner syndrome

22) 47,XX,+21. This karyotype refers to ………downs syndrome…………

24) Describe the karyotype of a Down syndromic female baby. 47,XX,+21

25) Describe the karyotype of a Down syndromic male baby.

26) Which chromosomal abnormality is the basis of Patau syndrome? 13 chromosome

27) Which numerical chromosome abnormality is the cause of Edwards syndrome? 18

30) Describe the standard karyotype of a healthy human female. 46,XX

31) Describe the standard karyotype of a healthy human male.

35) “Dosage compensation”. What does it mean in genetics? Why is it necessary? To

41) Give three examples of structural chromosome aberrations. Deletions, duplications,

44) Robertsonian translocation. Give an example of that aberration. An entire chromosome

45) Why is it important to make a precise chromosomal diagnosis of Down syndrome in a

48) What is meant by "dosage compensation"?

55) List at least four types of abnormalities in chromosome structure:

60) An arrangement of metaphase chromosomes according to their length and centromere

64) One of the consequences of X-chromosome inactivation is that a normal female is a

65) What is the Philadelphia chromosome?

5) The inheritance of hemophilia in a family is shown in the pedigree. What is the

Ch7 Transmission genetics 1/34

Genotype of II2 - XAXa

Ch7 Transmission genetics 2/34

10) Explain the term: recessive epistasis. Give a human example.

11) Explain the meaning of the term: linkage group.

12) In a Mendelian cross the 9:7 ratio of progenies in F2 is characteristic of

Ch7 Transmission genetics 3/34

16) Huntington disease is a rare degenerative human disease determined by a

18) Instead of the expected 9:3:3:1 ratios in an F2 generation from true-breeding

Ch7 Transmission genetics 4/34

Ch7 Transmission genetics 5/34

IAH IBH IAh IB h

25) Mice with a single X chromosome and no Y chromosome (an X0 chromosome

Ch7 Transmission genetics 6/34

27) Define the term “pleiotropy”. Give an example.

Remember: PKU is autosomal recessive

9) _RNA polymerase3___________ transcribes all tRNA genes and the 5S component

10) RNA polymerase _2_____ is responsible for transcribing all protein-

11) In eukaryotes, RNA polymerase _1_ is used exclusively in producing

21) Many eukaryotic genes are _housekeeping________ genes that encode

59) The various forms of a given gene are called allele__.

64) The _penetrance__ of a genetic disorder means the proportion of individuals