INTERNATIONAL UNIVERSITY FOR
SCIENCE & TECHNOLOGY
GENETICS lecture course
Dr. A. Rahmo
PhD. Biochemistry and Molecular biology USC
Incomplete Dominance
• The heterozygous
phenotype is distinct from
either homozygous
phenotype
• It may be an
intermediate phenotype
Familial Hypercholesterolemia
Lethal Alleles
• Many alleles that cause genetic diseases
are called "dominant" because
heterozygotes are affected. A common
example is achondroplasia, the most
common form of dwarfism, with a normal
length body trunk but shortened limbs.
Another in the Manx cat, which doesn't
have a tail.
• In fact, these genes would be better
described as partially dominant, because
the homozygotes are quite different from
the heterozygotes: homozygotes are
lethal.
Lethal Alleles
Some allele combinations are lethal
Pleiotropy
One gene has many symptoms or controls
several functions
This is quite common: genes make
proteins and often affect the overall
phenotype in subtle ways that affect many
different body systems.
Example:
porphyria variegata
Photo © North Wind Picture Archives
Pleiotropy of sickle-cell anemia
sickle cell
anemia causes
enlarged spleen,
muscle pain, low
red blood cell
count, resistance
to malaria, and
early death. All
of this is caused
by a single
mutation in one
of the
hemoglobin
genes
dominance relation vary
Cells break down
Oxygen drops
Cells break down before malarial has a chance to reproduce
Genetic Heterogeneity
Different genes can produce identical phenotypes
• Genes may encode for different enzymes in a biochemical pathway
• Genes may have redundant or overlapping function
• DNA sequences have identified new alleles
Examples:
Hearing loss
Albinism
Cleft palate
Clotting disorders
alzheimer disease
cystic fibrosis
lipoprotein lipase deficiency, familial
polycystic kidney diseases
Sex-Influenced Traits
A sex-influenced trait is an autosomal trait that is dominant in
one sex and recessive in the other.
Good examples: male pattern baldness in humans and horns in
sheep.
.
Pattern baldness is found in both sexes,
but is rarer in females. Females usually
get very thin hair all over, instead of the
classic receding hairline and bald spot on
top that men get.
Baldness is autosomal, but it is dominant in
males and recessive in females. Thus,
male heterozygotes are bald but female
heterozygotes have normal hair
Sex-influenced Traits
• Traits are those in which the phenotype
expressed by a heterozygote is influenced by
gender.
• Allele appears dominant in one gender and
recessive in the other
Example:
• Pattern baldness is a sex-influenced trait:
men
women
m/m
bald
bald
m/+
bald
unaffected
+/+
unaffected
unaffected
The Adams family
Sex-Limited Trait
• A sex-limited trait is expressed in one sex but not the
other. This is usually due to anatomical or
physiological limitations.
• May be autosomal or X linked
Examples:
• ability to produce milk is sex-limited, because only females have
breasts, the milk producing glands.
• Similarly, susceptibility of prostate cancer is limited to men,
because only males have a prostate gland.
• Beard growth
• Pregnancy phenotypes
• Sperm production levels
Genomic Imprinting
• Occurs when the expression of a gene differs
when the allele is transmitted maternally
versus paternally
• Function unknown, may play a role in
development
• Genes silenced by an epigenetic event
• Information not encoded by DNA
• Imprints maintained in mitotic divisions but lost
in meiosis
Genomic Imprinting
Importance of Genomic Imprinting
• Experiments suggest that it takes two opposite sex
parents to produce a healthy embryo
• Genes from female parent direct different activities from
the genes of the male parent
• May explain why cloning mammals is so difficult and the
offspring are almost always unhealthy
• Certain assisted reproductive technologies may produce
imprinting disorders
• May explain incomplete penetrance
Imprinting and Human Disease
Deletion on chromosome 15 reveals imprinting
• Inherited paternally
• Prader-Willi syndrome
• Inherited maternally
• Angelman syndrome
X Inactivation
• Females have two alleles for every gene on the X
chromosome but males have only one
• In mammals, X inactivation balances this inequality and
one X chromosome is randomly inactivated in each cell
• The XIST gene inactivates the chromosome and encodes
for RNA
• It alters phenotype but not genotype
• Inactivated X chromosomes form a Barr body
Cats Heterozygous for the Coat Color Gene
When the embryo has about 200 cells,
each cell randomly inactivates one
of its X’s, independently of the other
cells. The inactive X stays inactive
throughout the individual’s life,
through many cell generations.
A common example: tortoise shell cats
have patches of black and orange fur.
Almost all tortoiseshells are female.
Heterozygous for the X-linked coat color
gene, one allele black and the other
allele orange. Only 1 allele is expressed
in each cell, and patches on the fur
result from cell division of the original
embryonic cells that randomly chose an
X to inactivate.
A similar human condition: anhidrotic ectodermal dysplasia: absence
of sweat glands in the skin.
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•
•
•
•
•
•
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Organelle providing cellular energy
Contains small circular DNA
No crossing over or DNA repair
High exposure to free radicals
Mutation rate is greater than nuclear DNA
Has 37 genes, without noncoding
sequences
24 encode RNA molecules, 13 cellular
respiration
Mitochondrial genes are transmitted from
mother to all of her offspring
Mitochondrial
Inheritance
Heteroplasmy
•
•
Sometimes an individual has
more than one kind of
mitochondria. This is called
heteroplasmy. Since
mitochondria are divided
randomly during cell division,
different cells get different
proportions of the two types.
If one mitochondrial type is
mutant and the other is normal,
severity of symptoms will vary in
different tissues depending on
the proportions of the two types.
Heteroplasmy may cause
expressivity to vary widely and a lack
of symptoms until adulthood.
Ooplasmic transfer technique can
enable woman to avoid transmitting a
mitochondrial disorder.
Phenocopy
• Appears inherited but is caused by the environment
• May have symptoms that resemble an inherited trait or occur within
families
phocomelia
Examples:
Exposure to teratogens
Thalidomide causes limb defects
similar to inherited phocomelia.
Infection
Rubella in pregnant mothers causes
deafness mimicking inherited forms of
deafness.