IB BIOLOGY:GENETICS

3.0 Genes
 Genes
Essential Idea:

• Every living organism inherits a blueprint for

life from its parents.
• Pair up with a friend and discuss the above
statement in the next 3 minutes.
Understandings:

• A gene is a heritable factor that consists of a length of

DNA and influences a specific characteristic
• A gene occupies a specific position on a chromosome
• The various specific forms of a gene are alleles
• Alleles differ from each other by one or only a few
bases
• New alleles are formed by mutation
• The genome is the whole of the genetic information
of an organism
• The entire base sequence of human genes was
sequenced in the Human Genome Project
Applications:

• The causes of sickle cell anaemia, including a

base substitution mutation, a change to the
base sequence of mRNA transcribed from it
and a change to the sequence of a
polypeptide in haemoglobin
• Comparison of the number of genes in
humans with other species
 Genes
• DNA is the genetic blueprint which codes for, and determines, the
characteristics of an organism

• This includes the physical, behavioural and physiological features of

the organism

• DNA is packaged and organised into discrete structures called

chromosomes

• A gene is a sequence of DNA that encodes for a specific trait (traits

(may also be influenced by multiple genes)
• The position of a gene on a particular chromosome is called the
locus (plural = loci)
Genes and gene Loci
 Alleles

Alleles are alternative forms of a gene that code for

the different variations of a specific trait
• For example, the gene for eye colour has alleles
that encode different shades / pigments
• As alleles are alternative forms of the one gene,
they possess very similar gene sequences
• Alleles only differ from each other by one or a
few bases
Genes and potential allelic variations
 Gene Mutation

A gene mutation is a change in the nucleotide sequence of a

section of DNA coding for a specific trait.
• New alleles are formed by mutation

Gene mutations can be beneficial, detrimental or neutral

• Beneficial mutations change the gene sequence (missense
mutations) to create new variations of a trait
• Detrimental mutations truncate the gene sequence
(nonsense mutations) to abrogate the normal function of a
trait
• Neutral mutations have no effect on the functioning of the
specific feature (silent mutations)
Point mutations are changes to one base in the DNA
code and may involve either:

• The substitution of a base (e.g. ATG becomes

ACG)
• The insertion of a base (e.g. ATG becomes
ATCG)
• The deletion of a base (e.g. ATG becomes AG)
• The inversion of bases (e.g. ATG becomes AGT)
• Effects of Point Mutations

• Silent mutations occur when the DNA change

does not alter the amino acid sequence of the
polypeptide
• This is possible because the genetic code is
degenerate and certain codons may code for the
same amino acid

• Sickle cell anaemia is an example of a disease

caused by a single base substitution mutation
(GAG → GTG ; Glu → Val)
 Application of gene mutation: sickle anaemia

Sickle cell anaemia is an example of a disorder

caused by a gene mutation

• The disease allele arose from a base

substitution mutation – where a single base
was changed in the gene sequence
 Cause of Sickle Cell Anaemia

• Sickle cell anaemia results from a change to the 6th

codon for the beta chain of haemoglobin

• DNA: The DNA sequence changes from GAG to GTG on

the non-coding strand (CTC to CAC on the coding
strand)
• mRNA: The mRNA sequence changes from GAG to
GUG at the 6th codon position
• Polypeptide: The sixth amino acid for the beta chain of
haemoglobin is changed from glutamic acid to valine
(Glu to Val)
Cause of sickle cell anaemia
 Consequence of Sick Cell Anaemia

• The amino acid change (Glu → Val) alters the structure of

haemoglobin, causing it to form insoluble fibrous strands

• The insoluble haemoglobin cannot carry oxygen as

effectively, causing the individual to feel constantly tired

• The formation of fibrous haemoglobin strands changes the

shape of the red blood cell to a sickle shape
• The sickle cells may form clots within the capillaries,
blocking blood supply to vital organs and causing myriad
health issues
• The sickle cells are also destroyed more rapidly than normal
cells, leading to a low red blood cell count (anaemia)
 Sickle cell anaemia vs. Malaria
• Sickle cell anaemia is controlled by a single gene mutation (via
a base substitution to the haemoglobin beta chain gene)
• The sixth codon is mutated (GAG → GUG) which changes the
amino acid sequence (Glu → Val)
• Individuals who only possess the sickle cell allele will have
abnormally shaped red blood cells that are destroyed by the
spleen This leads to a reduction in red blood cells and a
variety of health complications associated with reduced blood
cell circulation
• Those who only possess the normal blood cell allele do not
suffer from sickle cell anaemia but are more susceptible to
malaria
• Malaria is caused by an endoparasite (Plasmodium
falciparum) which reproduces inside red blood cells (but not
sickle cells)
Incidence of Malaria

• In areas where malaria is common, there is a higher

incidence of people who carry both alleles (i.e. are
heterozygous)

• These individuals produce enough normal blood cells

to avoid the more severe effects associated with sickle
cell anaemia, but also produce enough sickle cells to
confer an increased resistance to the malarial parasite

• This condition whereby the presence of both alleles is

beneficial is known as heterozygous advantage
 GENOME
• The genome is the totality of genetic
information of a cell, organism or organelle

• This includes all genes as well as non-coding DNA

sequences (e.g. introns, promoters, short tandem
repeats, etc.)
• The human genome consists of:
• 46 chromosomes (barring aneuploidy)
• ~3 billion base pairs
• ~21,000 genes
 The Human Genome Project
The Human Genome Project (HGP) was an international cooperative venture
established to sequence the human genome

• The HGP showed that humans share the majority of their sequence, with
short nucleotide polymorphisms contributing diversity

• The completion of the Human Genome Project in 2003 led to many

outcomes:

• Mapping – The number, location, size and sequence of human genes is

now established
• Screening – This has allowed for the production of specific gene probes to
detect sufferers and carriers of genetic diseases
• Medicine – The discovery of new proteins have lead to improved
treatments (pharmacogenetics and rational drug design)
• Ancestry – Comparisons with other genomes have provided insight into
the origins, evolution and migratory patterns of man
 Gene Comparison
• The number of genes present in an organism will
differ between species and is not a valid indicator
of biological complexity

• The number of genes in a genome is usually

predicted by identifying sequences common to
genes

• These identifying regions may include expressed

sequence tags (ESTs) or sequences that are
homologous to known genes.
 Gene Comparison

• As scientists may use different approaches to

predicting gene numbers, final estimations
can vary significantly

• For instance, the number of genes in rice

(Oryza sativa) is estimated as being between
32,000 – 50,000
• The number of genes in humans is estimated
as being between 19,000 – 25,000
 Prokaryotic vs. Eukaryotic DNA
Prokaryotic DNA
• Is found freely in the
cytoplasm (within a region
called the nucleoid)
• Is naked (i.e. not bound with
proteins and therefore doesn’t
form chromatin)
• Genomes are compact
(contain little repetitive DNA
and no introns)
• Contains extra-chromosomal
plasmids
• Is circular in shape
Eukaryotic DNA
• Is contained within a nucleus
• Is bound to histone proteins
• Genomes contain large
amounts of non-coding and
repetitive DNA (including
introns)
• Do not contain plasmids
(but organelles such as the
mitochondria may contain
their own chromosomes)
• Are linear in shape
 Eukaryotic chromosome

The genetic material of eukaryotic cells consist

of multiple linear molecules of DNA that are
associated with histone proteins

• The packaging of DNA with histone proteins

results in a greatly compacted structure,
allowing for more efficient storage
Organisation of eukaryotic chromosomes can be summarised
as follows:

• DNA is complexed with eight histone proteins (an octamer)

to form a complex called a nucleosome
• Nucleosomes are linked by an additional histone protein
(H1 histone) to form a string of chromatosomes
• These then coil to form a solenoid structure (~6
chromatosomes per turn) which is condensed to form a 30
nm fibre
• These fibres then form loops, which are compressed and
folded around a protein scaffold to form chromatin
• Chromatin will then supercoil during cell division to form
chromosomes that are visible (when stained) under
microscope
 IDENTIFYING GENES
The first point of reference is a number (or letter) which denotes the chromosome (e.g. 7q31 refers to chromosome 7)
The second point of reference is a letter (p or q) to denote which arm the locus is positioned on (e.g. 7q31 is on the q arm)
The third point of reference is a number corresponding to the G band location (e.g. 7q31 is at the longitudinal position 31)
Genes are short stretches of DNA, which usually code for one
characteristic, and are located on chromosomes. The Figure
below shows an example of human chromosome 9. It has a length
of 145 million base pairs of DNA, which is approximately 4.5% of the
total human genome. Chromosome 9 has between 800 and 1,200
genes; it is also associated with a type of leukemia.
 Homologous chromosomes
• Sexually reproducing organisms inherit their genetic
sequences from both parents This means that these
organisms will possess two copies of each chromosome (one
of maternal origin ; one of paternal origin)
• These maternal and paternal chromosome pairs are called
homologous chromosomes. Homologous chromosomes are
chromosomes that share:
• The same structural features (e.g. same size, same banding
patterns, same centromere positions)
• The same genes at the same loci positions (while the genes
are the same, alleles may be different)
• Homologous chromosomes must be separated in gametes (via
meiosis) prior to reproduction, in order to prevent
chromosome numbers continually doubling with each
generation
 Autosome versus Heterosome
• In humans, sex is determined by a pair of
chromosomes called the sex chromosomes (or
heterosomes). Females possess two copies of a large
X chromosome (XX) Males possess one copy of an X
chromosome and one copy of a much shorter Y
chromosome (XY)
• The Y chromosome contains the genes for
developing male sex characteristics (specifically the
SRY gene)
• In its absence of a Y chromosome, female sex organs
will develop
 Autosome versus Heterosome
• The sex chromosomes are homologous in females (XX)
but are not homologous in males (XY)
• Hence the father is always responsible for determining
the sex of offspring:
• If the male sperm contains an X chromosome, the
growing embryo will develop into a girl
• If the male sperm contains a Y chromosome, the
growing embryo will develop into a boy.
• In all cases the female egg will contain an X
chromosome (as the mother is XX)
• The remaining chromosomes in the organism are called
autosomes (they do not determine sex)
 Karyograms
• Karyotypes are the number and types of chromosomes in a
eukaryotic cell – they are determined via a process that
involves:
• Harvesting cells (usually from a foetus or white blood cells of
adults)
• Chemically inducing cell division, then arresting mitosis while
the chromosomes are condensed
• The stage during which mitosis is halted will determine
whether chromosomes appear with sister chromatids or not
• The chromosomes are stained and photographed to generate
a visual profile that is known as a karyogram
• The chromosomes of an organism are arranged into
homologous pairs according to size (with sex chromosomes
shown last)
Application:
Use of karyograms to deduce sex and diagnose Down syndrome in
humans

Karyotyping will typically occur prenatally and is used to:

• Determine the gender of the unborn child (via identification of the sex
chromosomes)
• Test for chromosomal abnormalities (e.g. aneuploidies or translocations)

Down syndrome is a condition whereby the individual has three copies of

chromosome 21 (i.e. trisomy 21)

• It is caused by a non-disjunction event in one of the parental gametes

• The extra genetic material causes mental and physical delays in the way
the child develops

NB; USE CONNECT TO THE INTERNET TO MANIPULATE KARYOTYPE

DIAGRAMS.
A karyotype of a female with Trisomy 13
Karyotyping
Application:
• Description of methods used to obtain cells for karyotype analysis – e.g.
chorionic villi sampling and amniocentesis and the associated risks

Karyotyping is the process by which chromosomes are

organised and visualised for inspection
• Karyotyping is typically used to determine the gender of an
unborn child and test for chromosomal abnormalities
• Cells are harvested from the foetus before being chemically
induced to undertake cell division (so chromosomes are
visible)
• The stage during which mitosis is arrested will determine
whether chromosomes appear with sister chromatids
• Finally, chromosomes are stained and photographed,
before being organised according to structure
• The visual profile generated is called a karyogram
Ways of obtaining cells for Karyotype

1. Chorionic Villi Sampling

• Chorionic villi sampling involves removing a sample of the chorionic villus

(placental tissue) via a tube inserted through the cervix

• It can be done at ~11 weeks of pregnancy with a slight risk of inducing miscarriage
(~1%)

2. Amniocentesis

• Amniocentesis involves the extraction of a small amount of amniotic fluid

(contains fetal cells) with a needle

• It is usually conducted later than CVS (~16 weeks of pregnancy) with a slightly
lower risk of miscarriage (~0.5%)
Chromosome Size
Application:
Cairns’ technique for measuring the length of DNA molecules by autoradiography

Autoradiography

• Cells are grown in a solution containing radioactive thymidine (tritiated

thymidine – 3H-T)
• The tritiated thymidine is incorporated into the chromosomal DNA of the
cell (3H-T is used as thymidine is not present in RNA)
• The chromosomes are isolated by gently lysing the cells and fixing the
chromosomes to a photographic surface
• The surface is then immersed in a radioactively-sensitive emulsion
containing silver bromide (AgBr)
• The radiation released from the tritiated thymidine converts the Ag+ ions
in silver bromide into insoluble metal grains
• Following a period of exposure, excess silver bromide is washed away,
leaving the silver grains to appear as small black dots
• When the photographic film is developed, the chromosomal DNA can be
visualised with an electron microscope
Chromosome Length

• John Cairns pioneered a technique for measuring

the length of DNA molecules by autoradiography
• Previously, chromosome length could only be
measured while condensed during mitosis (very
inaccurate due to supercoiling)
• Cairns used autoradiography to visualise the
chromosomes whilst uncoiled, allowing for more
accurate indications of length
• By using tritiated uracil (3H-U), regions of active
transcription can be identified within the
uncoiled chromosome
Other Discoveries

• John Cairns was further able to use

autoradiography to demonstrate key events
which occur during chromosomal replication
• DNA replication involves formation of a
replication bubble (and prokaryotic replication
involves a single origin of replication)
• DNA replication is bi-directional (it occurs
independently at both ends of the replication
bubble)
Evidence for the Formation of Replication Bubbles (Prokaryotes)
Evidence that Replication is Bi-Directional
 Chromosome Number

• Chromosome number is a
characteristic feature of members
of a particular species

• Organisms with different diploid

numbers are unlikely to be able
to interbreed (cannot form
homologous pairs in zygotes) In
cases where different species do
interbreed, offspring are usually
infertile (cannot form functional
gametes)
• For instance, a horse (diploid =
64) and a donkey (diploid = 62)
may produce an infertile mule
(non-diploid = 63)
Application:

• Comparison of diploid chromosome numbers of Homo sapiens, Pan troglodytes, Canis familiaris,

Oryza sativa and Parascaris equorum

 Genome size

• Genome size can vary greatly between organisms and is not a valid
indicator of genetic complexity

• The largest known genome is possessed by the canopy plant Paris japonica
– 150 billion base pairs
• The smallest known genome is possessed by the bacterium Carsonella
ruddi – 160,000 base pairs

• As a general rule:

• Viruses and bacteria tend to have very small genomes

• Prokaryotes typically have smaller genomes than eukaryotes
• Sizes of plant genomes can vary dramatically due to the capacity for plant
species to self-fertilise and become polyploid
 Cell Division: Meiosis

Meiosis is the process by which sex cells (gametes) are made in the
reproductive organs

• It involves the reduction division of a diploid germline cell into four

genetically distinct haploid nuclei

• The process of meiosis consists of two cellular divisions:

• The first meiotic division separates pairs of homologous

chromosomes to halve the chromosome number (diploid →
haploid)
• The second meiotic division separates sister chromatids (created by
the replication of DNA during interphase)
 Sister Chromatids

Meiosis is preceded by interphase, during which

DNA is replicated (in the S phase) to produce two
genetically identical copies

• The two identical DNA molecules are identified as

sister chromatids, and are held together by a
single centromere
• The sister chromatids are separated during
meiosis II, following the separation of
homologous chromosomes in meiosis I
Meiosis consists of two divisions, both of which
follow the same stages as mitosis (prophase,
metaphase, anaphase, telophase)

• Meiosis is preceded by interphase, in which

DNA is replicated to produce chromosomes
consisting of two sister chromatids
• A second growth phase called interkinesis
may occur between meiosis I and II, however
no DNA replication occurs in this stage
Meiosis I

• The first meiotic division is a reduction division (diploid → haploid)

in which homologous chromosomes are separated

• P-I: Chromosomes condense, nuclear membrane dissolves,

homologous chromosomes form bivalents, crossing over occurs

• M-I: Spindle fibres from opposing centrosomes connect to bivalents

(at centromeres) and align them along the middle of the cell

• A-I: Spindle fibres contract and split the bivalent, homologous

chromosomes move to opposite poles of the cell

• T-I: Chromosomes decondense, nuclear membrane may reform,

cell divides (cytokinesis) to form two haploid daughter cells
Meiosis II

The second division separates sister chromatids (these chromatids may not be
identical due to crossing over in prophase I)

• P-II: Chromosomes condense, nuclear membrane dissolves, centrosomes move to

opposite poles (perpendicular to before)
• M-II: Spindle fibres from opposing centrosomes attach to chromosomes (at
centromere) and align them along the cell equator
• A-II: Spindle fibres contract and separate the sister chromatids, chromatids (now
called chromosomes) move to opposite poles
• T-II: Chromosomes decondense, nuclear membrane reforms, cells divide
(cytokinesis) to form four haploid daughter cells

• The final outcome of meiosis is the production of four haploid daughter cells

• These cells may all be genetically distinct if crossing over occurs in prophase I
(causes recombination of sister chromatids)
CROSSING OVER

• In prophase I, homologous chromosomes undergo a process called synapsis, whereby they

pair up to form a bivalent (or tetrad)

• The homologous chromosomes are held together at points called chiasmata (singular:
chiasma)

• Crossing over of genetic material between non-sister chromatids can occur at these
chiasmata

• As a result of this exchange of genetic material, new gene combinations are formed on
chromatids (recombination)

• Once chiasmata are formed, the homologous chromosomes condense as bivalents and then
are separated in meiosis

• If crossing over occurs then all four haploid daughter cells will be genetically distinct (sister
chromatids are no longer identical)
RANDOM ASSORTMENT
Orientation of pairs of homologous chromosomes prior to separation is random

• During metaphase I, homologous chromosomes line up at the equator as bivalents in one of two
arrangements:

• Maternal copy left / paternal copy right OR paternal copy left / maternal copy right

• This orientation of pairs of homologous chromosomes is random, as is the subsequent assortment

of chromosomes into gametes

• The final gametes will differ depending on whether they got the maternal or paternal copy of a
chromosome following anaphase I

• As this random assortment will occur for each homologous pair, the number of possible gamete
combinations are dependent on the number of homologous pairs

• Gamete combinations = 2n (where n represents the haploid number)

GENETIC VARIATION
Crossing over and random orientation promotes genetic variation

• Fusion of gametes from different parents promotes genetic variation

The advantage of meiotic division and sexual

reproduction is that it promotes genetic variation in
offspring

The three main sources of genetic variation arising from

sexual reproduction are:

• Crossing over (in prophase I)

• Random assortment of chromosomes (in metaphase I)
• Random fusion of gametes from different parents
Crossing Over

• Crossing over involves the exchange of segments of DNA between

homologous chromosomes during prophase I

• The exchange of genetic material occurs between non-sister

chromatids at points called chiasmata

• As a consequence of this recombination, all four chromatids that

comprise the bivalent will be genetically different

• Chromatids that consist of a combination of DNA derived from both

homologous chromosomes are called recombinants
• Offspring with recombinant chromosomes will have unique gene
combinations that are not present in either parent
Random Orientation

• When homologous chromosomes line up in metaphase I, their

orientation towards the opposing poles is random

• The orientation of each bivalent occurs independently, meaning

different combinations of maternal / paternal chromosomes can be
inherited when bivalents separate in anaphase I

• The total number of combinations that can occur in gametes is 2n

– where n = haploid number of chromosomes
• Humans have 46 chromosomes (n = 23) and thus can produce
8,388,608 different gametes (223) by random orientation
• If crossing over also occurs, the number of different gamete
combinations becomes immeasurable
Random Fertilisation

• The fusion of two haploid gametes

results in the formation of a diploid
zygote

• This zygote can then divide by

mitosis and differentiate to form a
developing embryo

• As meiosis results in genetically

distinct gametes, random fertilisation
by egg and sperm will always
generate different zygotes

• Identical twins are formed after

fertilisation, by the complete fission
of the zygote into two separate cell
masses
Non-Disjunction
Application: Non-disjunction can cause Down syndrome and other
chromosomal abnormalities

Non-disjunction refers to the chromosomes failing to

separate correctly, resulting in gametes with one extra, or
one missing, chromosome (aneuploidy)

• The failure of chromosomes to separate may occur via:

• Failure of homologues to separate in Anaphase I

(resulting in four affected daughter cells)
• Failure of sister chromatids to separate in Anaphase II
(resulting in only two daughter cells being affected)
Chromosomal Abnormalities

If a zygote is formed from a gamete that has experienced a

non-disjunction event, the resulting offspring will have extra
or missing chromosomes in every cell of their body

Conditions that arise from non-disjunction events include:

• Patau’s Syndrome (trisomy 13)

• Edwards Syndrome (trisomy 18)
• Down Syndrome (trisomy 21)
• Klinefelter Syndrome (XXY)
• Turner’s Syndrome / Fragile X (monosomy X)
Down Syndrome

Individuals with Down syndrome have three copies

of chromosome 21 (trisomy 21)

• One of the parental gametes had two copies of

chromosome 21 as a result of non-disjunction
• The other parental gamete was normal and had a
single copy of chromosome 21
• When the two gametes fused during fertilisation,
the resulting zygote had three copies of
chromosome 21
Application:

• Studies showing age of parents influences chances of non-disjunction

Studies show that the chances of non-disjunction increase as the age of the parents
increase

• There is a particularly strong correlation between maternal age and the

occurrence of non-disjunction events
• This may be due to developing oocytes being arrested in prophase I until ovulation
as part of the process of oogenesis

• Other studies also suggest that:

• The risk of chromosomal abnormalities in offspring increase significantly after a

maternal age of 30 (Table 1 / Figure 1)
• There is a higher incidence of chromosomal errors in offspring as a result of non-
disjunction in meiosis I (Figure 2)
• Mean maternal age is increasing, leading to an increase in the number of Down
syndrome offspring (Figure 3)
Studies into the development of chromosomal abnormalities
Inheritance
MENDEL’S LAWS

1. Law of Segregation: When gametes form, alleles are separated so

that each gamete carries only one allele for each gene

2. Law of Independent Assortment: The segregation of alleles for

one gene occurs independently to that of any other gene*

3. Principle of Dominance: Recessive alleles will be masked by

dominant alleles†

• * The law of independent assortment does not hold true for genes
located on the same chromosome (i.e. linked genes)
• † Not all genes show a complete dominance hierarchy – some
genes show co-dominance or incomplete dominance
Gametes are haploid sex cells formed by the process of meiosis – males produce
sperm and females produce ova

During meiosis I, homologous chromosomes are separated into different nuclei prior to cell
division
As homologous chromosomes carry the same genes, segregation of the chromosomes also
separates the allele pairs
Consequently, as gametes contain only one copy of each chromosome they therefore carry only
one allele of each gene
 MODES OF INHERITANCE

• The gene composition (i.e. allele combination) for a specific

trait is referred to as the genotype

• The genotype of a particular gene will typically be either

homozygous or heterozygous

• The observable characteristics of a specific trait (i.e. the

physical expression) is referred to as the phenotype

• The phenotype is determined by both the genotype and

environmental influences
 MODES OF INHERITANCE

Complete Dominance

Most traits follow a classical dominant / recessive pattern of inheritance, whereby one
allele is expressed over the other

• The dominant allele will mask the recessive allele when in a heterozygous state
• Homozygous dominant and heterozygous forms will be phenotypically
indistinguishable
• The recessive allele will only be expressed in the phenotype when in a
homozygous state

• When representing alleles, the convention is to capitalise the dominant allele and
use a lower case letter for the recessive allele

• An example of this mode of inheritance is mouse coat colour – black coats (BB or
Bb) are dominant to brown coats (bb)
Co-dominance

• Co-dominance occurs when pairs of alleles are both expressed

equally in the phenotype of a heterozygous individual

• Heterozygotes therefore have an altered phenotype as the alleles

are having a joint effect

• When representing alleles, the convention is to use superscripts for

the different co-dominant alleles (recessive still lower case)

• An example of co-dominance is feathering in chickens – black (CB)

and white (CW) feathers create a speckled coat (CBCW)
 Inheritance of ABO blood groups

Human red blood cells can be categorised into different blood groups based on the
structure of a surface glycoprotein (antigen)

• The ABO blood groups are controlled by a single gene with multiple alleles (A, B,
O)

• The A, B and O alleles all produce a basic antigen on the surface of red blood cells

• The A and B alleles are co-dominant and each modify the structure of the antigen
to produce different variants
• The O allele is recessive and does not modify the basic antigenic structure

• When representing blood group alleles, the letter I is used to represent the
different antigenic forms (isoantigens)

• A allele = IA ; B allele = IB ; O allele = i (recessive)

Inheritance of ABO blood groups

• As humans produce antibodies against foreign antigens,

blood transfusions are not compatible between certain
blood groups

• AB blood groups can receive blood from any other type (as
they already possess both antigenic variants on their cells)
• A blood groups cannot receive B blood or AB blood (as the
isoantigen produced by the B allele is foreign)
• B blood groups cannot receive A blood or AB blood (as the
isoantigen produced by the A allele is foreign)
• O blood groups can only receive transfusions from other O
blood donor (both antigenic variants are foreign)
The image part with relationship ID rId2 was not found in the file.
Skill:

• Comparison of predicted and actual outcomes of genetic crosses using real data
 Genetic Diseases
• Genetic diseases are caused when mutations to a gene (or genes)
abrogate normal cellular function, leading to the development of a disease
phenotype

• Genetic diseases can be caused by recessive, dominant or co-dominant

alleles

• An autosomal recessive genetic disease will only occur if both alleles are
faulty

• Heterozygous individuals will possess one copy of the faulty allele but
not develop disease symptoms (they are carriers)
• An example of an autosomal recessive genetic disease is cystic fibrosis
 Genetic Diseases
• An autosomal dominant genetic disease only requires one copy of a faulty allele to
cause the disorder

• Homozygous dominant and heterozygous individuals will both develop the full
range of disease symptoms
• An example of an autosomal dominant genetic disease is Huntington’s disease

• If a genetic disease is caused by co-dominant alleles it will also only require one
copy of the faulty allele to occur

• However, heterozygous individuals will have milder symptoms due to the

moderating influence of a normal allele
• An example of a genetic disease that displays co-dominance is sickle cell
anaemia
Application:

Inheritance of cystic fibrosis and Huntington’s disease

Cystic Fibrosis

• Cystic fibrosis is an autosomal recessive disorder

caused by a mutation to the CFTR gene on
chromosome 7
• Individuals with cystic fibrosis produce mucus which is
thick and sticky
• This mucus clogs the airways and secretory ducts of the
digestive system, leading to respiratory failure and
pancreatic cysts
• Heterozygous carriers who possess one normal allele
will not develop disease symptoms
Huntington’s Disease

• Huntington’s disease is an autosomal dominant disorder caused by a mutation to

the Huntingtin (HTT) gene on chromosome 4

• The HTT gene possesses a repeating trinucleotide sequence (CAG) that is usually
present in low amounts (10 – 25 repeats)

• More than 28 CAG repeats is unstable and causes the sequence to amplify
(produce even more repeats)

• When the number of repeats exceeds ~40, the huntingtin protein will misfold and
cause neurodegeneration

• This usually occurs in late adulthood and so symptoms usually develop noticeably
in a person’s middle age (~40 years)

• Symptoms of Huntington’s disease include uncontrollable, spasmodic movements

(chorea) and dementia
Understanding:

Many genetic diseases have been identified in humans but most are very rare

• There are over 4,000 identified single gene defects that lead to
genetic disease, but most are very rare

• Any allele that adversely affects survival and hence the capacity
to reproduce is unlikely to be passed on to offspring

• Recessive conditions tend to be more common, as the faulty allele

can be present in carriers without causing disease

• Dominant conditions may often have a late onset, as this does not
prevent reproduction and the transfer of the faulty allele
 Sex Linked Genes

Sex linkage refers to when a gene controlling a

characteristic is located on a sex chromosome (X or Y)

• The Y chromosome is much shorter than the X

chromosome and contains only a few genes (50 million
bp; 78 genes)
• The X chromosome is longer and contains many genes
not present on the Y chromosomes (153 million bp ; ~
2,000 genes)
• Hence, sex-linked conditions are usually X-linked - as
very few genes exist on the shorter Y chromosome
Understanding:
The pattern of inheritance is different with sex-linked genes due to their location on
sex chromosomes

• Sex-linked inheritance patterns differ from autosomal patterns due to the fact that the
chromosomes aren’t paired in males (XY)

• This leads to the expression of sex-linked traits being predominantly associated with a particularly
gender

• As human females have two X chromosomes (and therefore two alleles), they can be either
homozygous or heterozygous

• Hence, X-linked dominant traits are more common in females (as either allele may be dominant
and cause disease)

• Human males have only one X chromosome (and therefore only one allele) and are hemizygous for
X-linked traits

• X-linked recessive traits are more common in males, as the condition cannot be masked by a
second allele
The following trends always hold true for X-linked
conditions:

• Only females can be carriers (a heterozygote for a

recessive disease condition), males cannot be
heterozygous carriers
• Males will always inherit an X-linked trait from
their mother (they inherit a Y chromosome from
their father)
• Females cannot inherit an X-linked recessive
condition from an unaffected father (must
receive his dominant allele)
Application:
Red-green colour blindness and haemophilia as examples of sex-linked
inheritance

• Red-green colour blindness and haemophilia are both examples of

X-linked recessive conditions

• Consequently, they are both far more common in males than in

females (males cannot mask the trait as a carrier)

• When assigning alleles for a sex-linked trait, the convention is to

write the allele as a superscript to the sex chromosome (X)

• Haemophilia: XH = unaffected (normal blood clotting) ; Xh =

affected (haemophilia)
• Colour blindness: XA = unaffected (normal vision) ; Xa = affected
(colour blindness)
Haemophilia

• Haemophilia is a genetic disorder whereby the body’s ability to

control blood clotting (and hence stop bleeding) is impaired

• The formation of a blood clot is controlled by a cascade of

coagulation factors whose genes are located on the X chromosome

• When one of these factors becomes defective, fibrin formation is

prevented - meaning bleeding continues for a long time

• Different forms of haemophilia can occur, based on which specific

coagulation factor is mutated (e.g. haemophilia A = factor VIII)
Red-Green Colour Blindness
• Red-green colour blindness is a genetic
disorder whereby an individual fails to
distinguish between red and green colours
• This condition is caused by a mutation to the
red or green retinal photoreceptors, which are
located on the X chromosome
• Red-green colour blindness can be diagnosed
using the Ishihara colour test
• NB: Use the Ishihara colour test animation.
A gene mutation is a change to the base sequence of a gene that can affect the structure and
function of the protein it encodes

• Mutations can be spontaneous (caused by copying errors during DNA replication) or induced
by exposure to external elements

• Examples of factors which can induce mutations include:

• Radiation – e.g. UV radiation from the sun, gamma radiation from radioisotopes, X-rays from
medical equipment
• Chemical – e.g. reactive oxygen species (found in pollutants), alkylating agents (found in
cigarettes)
• Biological Agents – e.g. bacteria (such as Helicobacter pylori), viruses (such as human
papilloma virus)

• Agents which increase the rate of genetic mutations are called mutagens, and can lead to the
formation of genetic diseases

• Mutagens which lead to the formation of cancer are more specifically referred to as
carcinogens
• Check internet for more info on Hiroshima bombing and Chernobyl accident.
Analysis of Pedigree chart to deduce genetic
inheritance.
• A pedigree is a chart of the genetic history of a family over several
generations

• Males are represented as squares, while females are represented as

circles

• Shaded symbols mean an individual is affected by a condition, while

an unshaded symbol means they are unaffected

• A horizontal line between man and woman represents mating and

resulting children are shown as offshoots to this line

• Generations are labelled with roman numerals and individuals are

numbered according to age (oldest on the left)
Determining Autosomal Inheritance

• Dominant and recessive disease conditions may be identified only if certain

patterns occur (otherwise it cannot be confirmed)

Autosomal Dominant

• If both parents are affected and an offspring is unaffected, the trait must be
dominant (parents are both heterozygous)
• All affected individuals must have at least one affected parent
• If both parents are unaffected, all offspring must be unaffected (homozygous
recessive)

Autosomal Recessive

• If both parents are unaffected and an offspring is affected, the trait must be
recessive (parents are heterozygous carriers)
• If both parents show a trait, all offspring must also exhibit the trait (homozygous
recessive)
Determining X-Linked Inheritance

• It is not possible to confirm sex linkage from pedigree charts, as autosomal traits could potentially
generate the same results

• However certain trends can be used to confirm that a trait is not X-linked dominant or recessive

X-linked Dominant

• If a male shows a trait, so too must all daughters as well as his mother
• An unaffected mother cannot have affected sons (or an affected father)
• X-linked dominant traits tend to be more common in females (this is not sufficient evidence
though)

X-linked Recessive

• If a female shows a trait, so too must all sons as well as her father
• An unaffected mother can have affected sons if she is a carrier (heterozygous)
• X-linked recessive traits tend to be more common in males (this is not sufficient evidence though)