M.

03 NON-MENDELIAN GENETICS
Dr. Professor || September 2021
CYTOGENETICS
Transcribers: Delicano, Alleen Nove
Editors: Delicano, Alleen Nove

NON-MENDELIAN GENETICS
o Genotypes o Phenotypes
• Any inheritance pattern that don’t follow one or more laws o AA o lethal
of Mendelian Genetics
o Aa o achondroplasia
o Law of Segregation (First Law) o aa o normal height
• Maternal and paternal alleles for a trait separate
from one another during gamete formation and
reunite during fertilization o Cross 1

o Law of Independent Assortment (Second Law)

• During gamete formation, the alleles for different
traits segregate independently of one another
o Law of Dominance (Third Law)

• One dominant allele “masks” the expression of a

recessive allele

• OR genetic interactions that do not follow complete

dominance, are expressed together, or influence o 1/4 die as embryos (AA)
Survivors:
• each other’s expression\ 2/3 = achondroplasia (Aa)
1/3 = normal height (aa)
• Scientists observed that not all the traits predicted in test
crosses panned out as expected o Cross 2

• Mendel’s laws are still correct and did explain the basics
of genetics but real life is just more complicated than peas

I. ALTERATIONS TO GENE EXPRESSION

• Single genes seldom completely control a phenotype in

the way that Mendel’s experiments with peas suggested

• The underlying genotypic ratios persist, but other factors o All survive:
affect the phenotype (environmental or genotypic factors) 1/2 = achondroplasia
1/2 = normal height
• Seems to be exceptions to Mendel’s Laws but are not
B. Multiple Alleles
• The following are factors that influence single gene
o phenotypic ratios: Note that inheritance is still
• A gene can have multiple alleles because its sequence
Mendelian
can deviate in many ways.
o Lethal Alleles Multiple Alleles
o Incomplete Dominance and Codominance
o Epstatsis • Different allele combinations can produce variations in
o Penentrance and Expressitivity Pleiotropy the phenotype.
o Genetic Heterogeneity o PKU gene has hundreds of alleles resulting in
o Phenocopies
• four basic phenotypes.
A. Lethal Alleles o CF gene has over 1500 alleles
• Some CF genotypes can cause frequent severe
• Lethal genotype causes respiratory infections
death before the individual • Some causes only male infertility
can reproduce.
o Removes an expected C. Incomplete Dominance
progeny class following
a specific cross • One allele is not completely dominant over another

• Double dose of a dominant • Both traits are expressed

allele may be lethal.
o Examples • Traits are blended
• Achondroplastic together rather than
o dwarfism occurring distinctly from
• Mexican hairless dogs one another

o Alleles o Example:
• a = normal height (wild type) Blending in flowers:
• A = achondroplasia (mutant) o Homozygous
dominant = red flowers

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M.03 NON-MENDELIAN GENETICS
o Homozygous recessive = white flowers D. Codominance
ABO Blood Types Illustrate Codominance
Sample Cross:
o Heterozygotes = pink flowers Homozygous A father; Homozygous B mother
o Example: Familial hypercholesterolemia (FH)
AA x BB A A
o Heterozygote has approximately half the normal
number of receptors in the liver for LDL cholesterol
•Offspring will be
heterozygous AB since
B AB AB
both A and B will be
o Homozygous for the mutant allele totally lacks the expressed
receptor, and so their B AB AB
serum cholesterol
level is very high

o Sample Cross:
o Homozygous A father; Homozygous B mother

o AA x BB
o Offspring will be heterozygous AB since both A and B
will be expressed

Offspring from Parents with Blood Type A and Blood Type

D. Codominance B

o Both alleles for a particular trait are expressed equally

o When an organism is
heterozygous for a
o particular trait, both alleles
will be expressed at the
same time

o Ex. In certain varieties of

chicken, the allele for black
feathers is codominant with
the allele for white feathers
D. Codominance
o Homozygous Black father (B,B)
•Homozygous Black B B
o Homozygous White mother
father(B,B)
(B,B)
•Homozygous White
W BW BW Codominance Vs Incomplete
mother (B,B)
o Offspring will be heterozygous BW
•Offspring will be
heterozygous BW since
Dominance
Codominance Vs Incomplete Dominance
since both B and W will be both B and W will be W BW BW
expressed expressed

o In humans, one good example is the expression of ABO

antigens

o A and B alleles are codominant, thus both will be

expressed completely if a person is heterozygous

o ABO gene encodes a cell surface protein.

– IA allele produces A antigen.
– IB allele produces B antigen.
– i (IO) allele does not produce antigens.
E. Epistasis
o Alleles IA and IB are codominant, and both are completely
dominant to i. o Phenomenon where one gene affects the expression
of a second gene

o Interaction of two or more gene pairs at different loci

influence the same trait, but one allele has an
overriding effect on the phenotype

o Modifier Gene- a gene that affects expression of

another gene
Ex. Albinism, Bombay Phenotype

o Ex. Hair color in Labrador dogs is determined by two

sets of gene pairs:

A. Quantity of Pigment (Melanin) Produced

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M.03 NON-MENDELIAN GENETICS
Black –B • Expressivity – is the severity/degree of the
Brown – b phenotype

B. Pigment (Melanin) Deposition o Polydactyly is both incompletely penetrant and

Turned On – E variably expressed
Turned Off – e
E. Epistasis
Black Brown Yellow
BBEE G. Pleiotropy
BbEE bbEE BBee
BBEe bbEe Bbee • Phenomenon where one gene controls several
BbEe bbee functions or has more than one effect

Example:
o White Mohan Tiger
• Same allele for
absence of melanin
production gives rise
to crossed eyes

o Phenylketonuria (PKU)
o In Humans: • Same allele for toxic
Ex. Bombay phenotype substances gives rise
to light colored hair
o H gene is epistatic to the I gene
o H protein places a molecule at the cell surface to o Marfan Syndrome
which the A or B antigens are attached • Defect in fibrillin abundant
o Without H protein the A or B antigens cannot be in lens of the eyes, in the
attached to the surface of the RBC aorta, and in bones of the
• hh genotype = no H protein limbs
o All hh genotypes have the phenotype of type O, • Symptoms are: Lens
although the ABO blood group can be anything (A, B, dislocation Long limbs
AB, or O) Spindly fingers Caved-in
chest
F. Penetrance and Expressivity
H. Genetic Heterogeneity
o Penetrance- the percentage of individuals who have
a certain genotype and show the expected o Different genes can produce identical phenotypes
phenotype • Leber congenital amaurosis- 21 genes
involved
o All-or-none expression of a single gene • Hearing loss—132 autosomal recessive forms
– Mendel traits penetrance = 100 % • Osteogenesis imperfecta—At least two
– Some traits penetrance is less than 100% different genes involved
(incompletely penetrant) • Alzheimer’s disease—At least four different
genes involved
o Decreased penetrance or “low penetrance” means • Retinitis Pigmentosa (RP)
that some people inherit genotype and yet do not • Can be Autosomal Dominant, recessive, X-
show the phenotype linked depending on which gene(s) individual
carries
o Calculation:
Number of individuals who have genotype and expected o Genes may encode enzymes that catalyze the same
phenotype Total number of individuals who have genotype biochemical pathway, or different proteins that are
(any phenotype) part of the pathway.

o Expressivity- the severity or extent of the Many Routes to Blindness

phenotype an individual shows

o Sometimes the same genotype will produce different

“degrees” of phenotype in individuals (variable
expressivity)

o Ex. Hypercholesterolemia
– Some individuals have extremely high cholesterol
from birth, others can control with diet and exercise
and lead normal lives I. Phenocopy

o Both follow Mendel’s laws BUT phenotypic ratio is o Trait that appears inherited but is caused by the
affected environment
o May have symptoms that resemble an inherited trait
o Both have to do with “amount” phenotype present or occur within families
• Penetrance – is all or none, person is affected o Examples:
with disease or not • Exposure to teratogens

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M.03 NON-MENDELIAN GENETICS Three-person Babies
Thalidomide causes limb defects similar to inherited • Doctors take a donor egg from a
healthy woman and remove the
phocomelia o Doctorsnucleus-leaving
take a donor behindegg from a
an empty
healthyshell
womanwith and
plenty remove the
of mitochondria
• Infection inside
nucleus-leaving behind an empty
AIDS virus can be passed from mother to child, Next,
shell•with they of
plenty take the nucleus out
mitochondria
looking like it is inherited inside of one of the biological mom’s
eggs and implant it in the empty
Table 5.1 Factors That Alter Single- egg shell
Table 5.1 Factors That Alter Single- Gene Phenotypic Next,• they
Thattake the newnucleus out
Ratios
Gene Phenotypic Ratios o
of one of
way, the
the biological
egg has
mom’s
healthy mitochondrial DNA from
eggs andtheimplant
donor mom, it in the
plusempty
all the
Phenomenon Effect on Phenotype Example
nuclear DNA that actually makes Dr. John Zhang and his colleagues
egg shell used the method to make 5
Lethal alleles A phenotypic class does not survive to reproduce. Achondroplasia
up a person from its biological embryos- of which one developed
mom
Many variants or degrees of a phenotype are o That way, the new egg has normally on a Jordanian mom with
Multiple alleles
possible.
Cystic fibrosis • The egg can then be fertilized, Leigh Syndrome
healthyimplanted,
mitochondrial DNA from
and carried to term
A heterozygote’s phenotype is intermediate Familial
Incomplete dominance
between those of the two homozygotes. hypercholesterolemia the donor mom, plus all the nuclear DNA that actually
A heterozygote’s phenotype is distinct from and makes up a person from its biological mom
Codominance not intermediate between those of the two ABO blood types
homozygotes.

One gene masks or otherwise affects another’s

o The egg can then be fertilized, implanted, and carried to
Epistasis Bombay phenotype
phenotype.
term
Table 5.1 Factors That Alter Single-
Penetrance
Some individuals with a particular genotype do
not have the associated phenotype.
Polydactyly

Appearance of Skeletal Muscle Fibers in Mitochondrial

Gene Phenotypic Ratios
Expressivity
A genotype is associated with a phenotype of
varying intensity.
Polydactyly
Disease
© McGraw-Hill Education. 5-36
Phenomenon Effect on Phenotype Example

The Phenotype includes many symptoms, with

Pleiotrophy Marfan syndrome
different subsets in different individuals.

An environmentally caused condition has

Phenocopy symptoms and a recurrence pattern similar to Infection
those of a known inherited trait.

Genotypes of different genes cause the same

Genetic heterogeneity Osteogenesis imperfecta
phenotype.

II. NON-MENDELIAN INHERITANCE

A. Extranuclear Inheritance
a) Heteroplasmy
B. Gene Linkage © McGraw-Hill Education. 5-37

C. Sex-linked traits

A. Extranuclear Inheritance Aa. Heteroplasmy

o Cells contain a special type of DNA called o Condition where the mtDNA sequence is not the same in
mitochondrial DNA all copies of the genome
found in mitochondria • Mitochondrion will have different alleles for the
same gene
o Mitochondrial DNA is
passed down from o At each cell division, the mitochondria are distributed at
mother to child random into daughter cells

o The mitochondria in o If an oocyte is heteroplasmic, differing number of copies

sperm of a mutant mtDNA may be transmitted
• Phenotype reflects the proportion of
o cells don’t make it into the mitochondria bearing the mutation
egg

o Mitochondrial diseases are rare; but when they do

happen, any child that a woman has will also have the
disease because mitochondria is passed on unchanged
from mother to child

Mitochondrial Disorders

• Mitochondrial genes encode proteins that participate in

protein synthesis and energy production Mitochondarial DNA Reveals Past

• Several diseases result from mutations in mtDNA o mtDNA provides a powerful forensic tool used to:
• Examples: • Link suspects to crimes
o Mitochondrial myopathies—Weak and flaccid muscles • Identify war dead
o Leber optical atrophy—Impaired vision • Support or challenge historical records
o Ooplasmic transfer technique can enable woman to • Example—Identification of the son of Marie
avoid transmitting a mitochondrial disorder Antoinette and Louis XVI
•
o mtDNA is likely to survive extensive damage and
Three-person Babies cells have many copies of it
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M.03 NON-MENDELIAN GENETICS B. Gene Linkage
B. Gene Linkage

o Directly violates the Law of Independent Assortment

o Sometimes alleles of certain genes are inherited

together, rather than segregating independently

o Genes located in close proximity to each other on the

same chromosome are more likely to be inherited
together instead of assorting independently
B. Gene Linkage
• example,
• For For example, in classic
in classic Mendelian
Mendelian law of independent
law of independent
assortment,
assortment, a dihybrid
a dihybrid cross between
cross between 2 heterozygous
2 heterozygous
fruit flies
fruit (BbEe X BbEe)
flies (BbEe X should
BbEe) yield offspring
should with 9 with 9
yield offspring
possible genotypes
possible and 4 phenotypes
genotypes and 4 phenotypes
© McGraw-Hill Education. 5-52

C. Sex-linked Traits
LEGEND
B-brown body o Traits that are coded for by genes that are located on
b- black body
the sex chromosomes
E- red eyes
e- brown eyes • Usually found on the X chromosomes

RATIO= 9:3:3:1 o Sex-linked diseases are more common in males

Examples:
• Red-green colorblindness
•
B. Gene Linkage
But certain traits such as body color and wing length
• Duchenne Muscular
Dystrophy
• Butdo certain traits such
not follow the as body color
classic and wing
Mendelian length do
genetics not
when
follow the classic Mendelian genetics when test-crossed: • Hemophilia
test-crossed:
LEGEND o Color vision deficiency (also
B- brown known as color blindness)
b- black represents a group of
V- long wings conditions that affect the
v- short misshapen perception of color. Red-
wings green color blindness is the
most common form of color
TEST CROSS: vision deficiency
BbVv X bbvv
REVIEW QUESTIONS

o Identify what phenomena is at work for each of

o The results reveal that brown body color and long wings the situations described below:
are more likely to be inherited together (BV) A woman with severe neurofibromatosis type 1 has
brown spots on her skin and several large tumors
o Also, black body is more likely to be inherited together beneath her skin. A genetic test shows that her son
with short wings (bv) has the disease-causing autosomal dominant allele,
but has no symptoms
o That is because the body color and wing length genes
are “linked”, which means they are located very close to Ans:
each other on the same chromosome
o Identify what phenomena is at work for each of
o A haplotype is a group of genes within an organism that the situations described below:
was inherited together from a single parent A man and woman have six children. They also had
two stillbirths.
• In humans:
o Genes that are Ans:
close on the
same o Identify what phenomena is at work for each of
chromosome the situations described below:
are said to be A woman with dark brown skin uses uses a
linked. bleaching agent that darkens her fingertips and ears,
making her look like she has the inherited disease
o Linked genes do alkaptonuria
not assort
independently in Ans:
meiosis.
• Usually
inherited
together
when the

chromosome is packaged into a gamete

• Do not produce typical Mendelian ratios

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