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More Genetics!
Extensions: Going beyond
Mendel…
X-Linked Alleles
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Genes carried on autosomes are said to be
autosomally linked
Genes carried on the female sex
chromosome (X) are said to be X-linked (or
sex-linked)
X-linked genes have a different pattern of
inheritance than autosomal genes have
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The Y chromosome is blank for these genes
Recessive alleles on X chromosome:
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Follow familiar dominant/recessive rules in females
(XX)
Are always expressed in males (XY), whether
dominant or recessive
Males said to be monozygous for X-linked genes
Sex-Linked Trait
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If a gene is found only on the X chromosome and not the
Y chromosome, it is said to be a sex-linked or X-linked
trait.
Because the gene controlling the trait is located on the
sex chromosome, sex linkage is linked to the gender of
the individual.
Usually such genes are found on the X chromosome. The
Y chromosome is thus missing such genes.
Females will have two copies of the sex-linked gene while
males will only have one copy of this gene.
If the gene is recessive, then males only need one such
recessive gene to have a sex-linked trait rather than the
customary two recessive genes for traits that are not
sex-linked. This is why males exhibit some traits more
frequently than females.
Sex-Linked Traits (X-linked Traits)


The chromosomes that determine gender.
 Males XY
 Females XX
Because the X chromosome contains many more
genes than the Y chromosome, males are more
likely to express any mistake that may be on
the X chromosome.
 Red-green color blindness
 Hemophilia
 Duchenne muscular
dystrophy
Drosophila Chromosomes
Eye Color in Fruit Flies
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Fruit flies (Drosophila melanogaster) are common
subjects for genetics research
They normally (wild-type) have red eyes
A mutant recessive allele of a gene on the X chromosome
can cause white eyes
Possible combinations of genotype and phenotype:
XR XR
XR Xr
XrXr
XR Y
Xr Y
Genotype
Homozygous Dominant
Heterozygous
Homozygous Recessive
Monozygous Dominant
Monozygous Recessive
Phenotype
Female
Red-eyed
Female
Red-eyed
Female
White-eyed
Male
Red-eyed
Male
White-eyed
X-Linked
Inheritance
Human X-Linked Disorders:
Red-Green Color Blindness

Color vision In humans:
 Depends three different classes of cone cells in the
retina
 Only one type of pigment is present in each class of
cone cell
 The gene for blue-sensitive is autosomal
 The red-sensitive and green-sensitive genes are on
the X chromosome
 Mutations in X-linked genes cause RG color
blindness:
 All males with mutation (XbY) are colorblind
 Only homozygous mutant females (XbXb) are
colorblind
 Heterozygous females (XBXb) are asymptomatic
carriers
Red-Green
Colorblindness
Chart
X-Linked
Recessive
Pedigree
Human X-Linked Disorders:
Muscular Dystrophy

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Muscle cells operate by release and rapid sequestering of
calcium
Protein dystrophin required to keep calcium sequestered
Dystrophin production depends on X-linked gene
A defective allele (when unopposed) causes absence of
dystrophin
 Allows calcium to leak into muscle cells
 Causes muscular dystrophy
All sufferers male
 Defective gene always unopposed in males
 Males die before fathering potentially homozygous
recessive daughters
Human X-Linked Disorders:
Hemophilia
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“Bleeder’s Disease”
Blood of affected person either refuses to clot or
clots too slowly
 Hemophilia A – due to lack of clotting factor IX
 Hemophilia B – due to lack of clotting factor VIII
Most victims male, receiving the defective allele from
carrier mother
Bleed to death from simple bruises, etc.
Factor VIII now available via biotechnology
Human X-Linked Disorders:
Fragile X Syndrome

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Due to base-triplet repeats in a gene on the X
chromosome
CGG repeated many times
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6-50 repeats – asymptomatic
230-2,000 repeats – growth distortions and mental
retardation
Inheritance pattern is complex and unpredictable
Additional Terminology

Pleiotropy
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Codominance
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A gene that affects more than one
characteristic of an individual
Sickle-cell (incomplete dominance)
More than one allele is fully expressed
ABO blood type (multiple allelic traits)
Epistasis


A gene at one locus interferes with the
expression of a gene at a different locus
Human skin color (polygenic inheritance)
Incomplete Dominance

The phenotype of a heterozygote (CRCW)
is intermediate between the phenotypes
of the two types of homozygotes (CRCR
and CWCW).
In incomplete
dominance there will
be three phenotypes,
one for each possible
combination, not two
as in a typical
dominant/recessive
situation!
Incomplete
Dominance
Example of
incomplete
dominance:
Snapdragons!
Figure 11.14
Assessment of dominance depends on
the level of analysis!
A heterozygote may display a dominant phenotype at the
organismal level, but at a biochemical level may show
incomplete dominance.
Tay-Sachs disease: caused by absence of
an enzyme, hexosaminidase A (Hex-A)
Homozygous dominant: normal levels of Hex-A, normal
development of child
Homozygous recessive: no Hex-A, death of child by age 5
Heterozygote:1/2 normal levels of Hex-A, normal
development of child
Assessment of dominance depends on the level of
analysis!
Survival
die
live
Complete
Dominance
HexA+/ HexA+
HexA+/ HexA-
HexA-/ HexATay-Sachs
live
Amount of
hexaminidase
die
HexA+/ HexA+
HexA+/ HexA-
HexA- codes for a nonfunctional enzyme.
Incomplete
Dominance
HexA-/ HexATay-Sachs
Co-Dominance
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describes a relationship where the
distinct phenotypes caused by each
allele are both seen when both alleles
are present.
Ex. Blood Type (also shows multiple
alleles)
Sickle Cell Anemia
Sickle Cell Anemia
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RBCs sickle
shaped
Anemia
Pain
Stroke
Leg ulcers
Jaundice
Gall stones
Spleen, kidney
& lungs
Blood cells
Sickle cell anemia
http://www.netwellness.org/ency/imagepages/1223.htm
Blood smear (normal)
http://137.222.110.150/calnet/cellbio/cellbio.htm
Sickle Cell Anemia
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Normal red blood cells
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People with sickle cell conditions make a different form of
hemoglobin A called hemoglobin S (S stands for sickle).
Hemoglobin S red blood cells
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do not live as long as normal red blood cells (normally about 16 days)
become stiff, distorted in shape and have difficulty passing through the
body’s small blood vessels.
When sickle-shaped cells block small blood vessels, less blood can reach
that part of the body. Tissue that does not receive a normal blood flow
eventually becomes damaged. This is what causes the complications of
sickle cell disease.
Normal hemoglobin: AA
Sickle Cell Trait: AS
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contain hemoglobin A
are soft and round and can squeeze through tiny blood tubes (vessels)
live for about 120 days before new ones replace them
Sickle Cell trait (AS) both hemoglobin A and S are produced in the red
blood cells. People with sickle cell trait are generally healthy.
Sickle Cell Disease: SS
Multiple Alleles
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Genes with more then two alleles in the
population
any individual possesses only two such alleles (at
equivalent loci on homologous chromosomes.)
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Alleles for Blood Type (A, B, O)
Human-Leukocyte-Associated antigen (HLA)
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HLA genes code for protein antigens that are expressed in
most human cell types and play an important role in immune
responses. These antigens are also the main class of molecule
responsible for organ rejections following transplantations—
thus their alternative name: major histocompatibility complex
(MHC) genes.
There are over 100 alleles for HLA!
Human ABO Blood Groups
•Gene “I” specifies which sugar is found on the
outside of red blood cells
• 3 alleles are present in the human population:
•IA = N-acetyl-galactosamine
•IB = galactose
•i (also referred to as o) = no sugar present
• This gives us 6 possible genotypes
The Human ABO Blood Group System
Immunology 101
(In a nutshell)
•Sugar on the blood cell is an antigen* (A, B,
A and B, or none)
•Your immune system thinks your own
antigens are fine
•Your immune system makes antibodies
against non-self antigens
•Antibodies recognize and target cells with
antigens for destruction
*something that elicits an immune response
There are 3
different
alleles, IA,
IB, and i
•Allele IA makes a
cell surface
antigen,
symbolized with a
triangle
• IB makes a
different antigen,
symbolized as a
circle
• i makes no
antigen
A little more scientific in
perspective…
Multiple Alleles: ABO Blood Type
Type A blood
transfused into
Type B personnot OK!
Type B blood
transfused into
Type B person –
OK!
A medical
problem - some
blood
transfusions
produce lethal
clumping of
cells.
The antigens (A
and B) cause
antibodies to be
produced on by
individuals who
do not have
them!
Another Example of Multiple Alleles
Polygenic Inheritance
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Occurs when a trait is governed by two or
more genes having different alleles
Each dominant allele has a quantitative effect
on the phenotype
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These effects are additive
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Result in continuous variation of phenotypes
Polygenic inheritance:
additive effects (essentially,
incomplete dominance) of multiple genes on a single trait
(phenotypic appearance)
AA = dark
Aa = less dark
aa - light
Think of each
“capital” allele
(A, B, C) as
adding a dose of
brown paint to
white paint.
Each dominant allele
contributes a small but equal
effect to the phenotype.
By the way…
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The genetics of human eye color is
actually complicated and is not
dictated solely by the simple
dominant-recessive actions of two
alleles of one gene. There are
multiple genes (with multiple alleles
of each gene) involved, and the
interactions of these genes have
not been clearly elucidated
(understood/explained).
This is clearly evidenced by the
enormous variation in human eye
color that does not always follow
the simplified model. People
generally have flecks, rays and
“splotches” of browns, blues,
ambers and greens that overlay the
background color.
Inheritance of Eye Color in Humans
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The inheritance of brown or blue eyes in humans is a
result of two copies of a gene that codes for pigment
production.
There are four alleles for eye pigmentation, two that
code to produce pigment and two that code for "no
pigment".
We have an increase in variation within the population
because the heterozygotes phenotypes of the genes
involved are expressed (codominance).
The eye color alleles code for the production of a
yellow-brown pigment*
*There is also a yellow overlay gene
which, when combined with the basic
pigment gene, alters light brown to
hazel and light blue to green.
First Iris Layer
Pigment
• AA = Produce lots of
pigment
• Aa = Produce some
pigment
• aa = Do not produce
pigment
Second Iris Layer
Pigment
• BB = Produce lots of
pigment
• Bb = Produce some
pigment
• bb = Do not produce
pigment
Eye Color
What does this tell you about the
inheritance of height?
Birds of a Feather?
Pleiotropy
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From the Greek words
meaning “many” and
“influences”
The impact of a single
gene on more than one
characteristic

Mendel also recognized this
effect. He observed that
pea plants with red flowers
had red coloration where
the leaf joined the stem,
but that their seed coats
were gray in color. Plants
with white flowers had no
coloration at the leaf-stem
juncture and displayed
white seed coats. These
combinations were always
found together, leading
Mendel to conclude that
they were likely controlled
by the same hereditary unit
(i.e., gene).
Examples of pleiotropy include:
The albino condition lack pigment in their skin and hair
 Affects eye and skin sensitivity to light in many
animals
 Also have crossed eyes at a higher frequency than
pigmented individuals.
 This occurs because the gene that causes albinism
can also cause defects
in the nerve connections
between the eyes and
the brain.
 These two traits are not
always linked, again
showing the complexity
of genetic interactions in
determining phenotypes.
Even the environment has an impact on some genes!
Environmental effects
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environment often influences phenotype
the norm of reaction = phenotypic range due to
environmental effects
norms of reactions are often broadest for
polygenic characters.
Flower color in hydrangia
determined by pH of soil!
•Blue hydrangia require acidic pH
•Pink hydrangia require basic pH
Temperature can affect gene
expression!
Let’s Experiment
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The classic study on environmental control of
gene expression was done with the pigmentation
gene of Siamese cats and Himalayan cats and
rabbits.
Typically, the animal's extremities are pigmented
while the body core remains unpigmented or
cream colored.
The pigmentation gene is activated when the
temperature falls below a certain point.
To demonstrate that the pattern was
temperature controlled, the backs of rabbits
were shaved and ice packs placed on the shaved
portion.
When new fur grew, it was pigmented.
Cold controls melanin production the
Himalayan rabbits… why go black in the cold?
Temperature
Environmental effects:
effect of temperature
on pigment expression in Siamese cats
Burrrrrr
It’s getting hot in
here….
Even diet can make a difference!
Where’s
the beef?
Caterpillar fed Oak flowers
Caterpillar fed Oak leaves
Got Air?
Epistasis
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Genes whose actions are required for other genes to
be expressed.
This has an effect on mammalian hair color. The
dominant allele of this gene allows pigment to be
produced, while the recessive allele does not. A
second gene controls the distribution of the pigment
in the hair.
Example: Coat color in Labrador Retrievers
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BB or Bb-----------> Black
bb-------------------->Chocolate
Where do Yellow Labs come from?
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Yellow vs. Dark (Black or Chocolate) is controlled by the
Extension Gene (E)
EE or Ee--------->dark color
ee------------------>yellow (regardless of BB or bb)
Practice Problem…
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BbEe X BbEe
Set up this cross and determine the
ratios of the offspring
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Epistatis in Mice:
 Mice also have black or brown-pigmented fur
depending on the inheritance of a gene for
pigmentation. A second, independent gene prevents the
distribution of any pigment in the fur. This gene, when
recessive, results in white mice.
Epistasis
in horses
In horses, brown coat color
(B) is dominant over tan (b).
Gene expression is
dependent on a second gene
that controls the deposition
of pigment in hair. The
dominant gene (C) codes for
the presence of pigment in
hair, whereas the recessive
gene (c) codes for the
absence of pigment. If a
horse is homozygous
recessive for the second
gene (cc), it will have a white
coat regardless of the
genetically programmed coat
color (B gene) because
pigment is not deposited in
the hair.
A Comparison
More Mostly Human
Genetics
Chromosome Number: Polyploidy
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Polyploidy
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Occurs when eukaryotes have more than 2n
chromosomes
Named according to number of complete sets of
chromosomes
Major method of speciation in plants
 Diploid egg of one species joins with diploid pollen
of another species
 Result is new tetraploid species that is self-fertile
but isolated from both “parent” species
 Some estimate 47% of flowering plants are
polyploids
Often lethal in higher animals
Human Triploidy
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Triploidy is the third most
frequent chromosomal
anomaly and is responsible
for 15-18% of spontaneous
abortions (Dyban and
Baranov, 1990). Only 1 in
1,200 triploid fetuses live
after birth, although for a
very short time. The
frequency of triploidy in
live births is 1/10,000
(Jacobs et al., 1974), and
males represent 51-69% of
the cases (McFadden and
Langlois, 2000).
Most common cause is
double fertilization.
Chromosome Number: Aneuploidy
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Monosomy (2n - 1)
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Diploid individual has only one of a particular chromosome
Caused by failure of synapsed chromosomes to separate
at Anaphase I (nondisjunction)
Trisomy (2n + 1) occurs when an individual has
three of a particular type of chromosome

Diploid individual has three of a particular chromosome
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Also caused by nondisjunction
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This usually produces one monosomic daughter cell and
one trisomic daughter cell in meiosis I
Down syndrome is trisomy 21
Nondisjunction
Trisomy 21
a.k.a. Down’s Syndrome
Chromosome Number:
Abnormal Sex Chromosome Number
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Result of inheriting too many or too few
X or Y chromosomes
Caused by nondisjunction during
oogenesis or spermatogenesis
Turner Syndrome (XO)
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Female with single X chromosome
Short, with broad chest
Can be of normal intelligence and function
with hormone therapy
Chromosome Number:
Abnormal Sex Chromosome Number
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Klinefelter Syndrome (XXY)
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Male with underdeveloped testes and
prostate; some breast overdevelopment
Long arms and legs; large hands
Near normal intelligence unless XXXY,
XXXXY, etc.
No matter how many X chromosomes,
presence of Y renders individual male
Turner and Klinefelter Syndromes
Chromosome Number:
Abnormal Sex Chromosome Number
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Poly-X females
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XXX simply taller & thinner than usual
Some learning difficulties
Many menstruate regularly and are fertile
More than 3 Xs renders severe mental
retardation
Jacob’s syndrome (XYY)
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Tall, persistent acne, speech & reading
problems
Abnormal Chromosome Structure
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Deletion
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Missing segment of chromosome

Lost during breakage
Translocation
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A segment from one chromosome moves to
a non-homologous chromosome
Follows breakage of two nonhomologous
chromosomes and improper re-assembly
Deletion,
Translocation,
Duplication,
and Inversion
Abnormal Chromosome Structure

Duplication
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A segment of a chromosome is repeated in
the same chromosome
Inversion

Occurs as a result of two breaks in a
chromosome

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The internal segment is reversed before reinsertion
Genes occur in reverse order in inverted
segment
Inversion Leading to
Duplication and Deletion
Abnormal Chromosome Structure

Deletion Syndromes
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Williams syndrome - Loss of segment of
chromosome 7
Cri du chat syndrome (cat’s cry) - Loss of
segment of chromosome 5
Translocations
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Alagille syndrome
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Some cancers
Williams Syndrome
Williams Syndrome


Williams syndrome is a
genetic disorder
characterized by mild
mental retardation,
distinctive facial
appearance, problems with
calcium balance, and blood
vessel disease.
Caused by missing part of
the genetic material on one
copy of chromosome 7,
deleting approximately 25
genes.
Alagille Syndrome
Alagille Syndrome
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Reciprocal translocation.
The JAG1 and NOTCH2 genes provide
instructions for making proteins that fit
together to trigger signaling between
neighboring cells during embryonic development.
This signaling influences how the cells are used
to build body structures in the developing
embryo.
Mutations in either the JAG1 gene or NOTCH2
gene probably disrupt the signaling pathway. As
a result, errors may occur during development,
especially affecting the heart, bile ducts in the
liver, spinal column, and certain facial features.
Liver problems most common issue.
The End…