Transcript More Genetics!

More Genetics!
Extensions: Going beyond
Mendel…
Sex-Linked Trait
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Genes on autosomes are autosomally linked.
If a gene is found only on the X chromosome and not
the Y chromosome, it is 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 gene is recessive:
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males only need one recessive gene to have a sex-linked trait
This is why males exhibit some traits more frequently than
females.
Sex-Linked Traits (X-linked Traits)
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Sex-Linked
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The chromosomes that determine gender.
 Males XY (monozygous)
 Females XX (typical dominant/recessive)
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
Sex-Linked
Eye Color in Fruit Flies
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Sex-Linked
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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:
X R XR
X R Xr
X rXr
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
Sex-Linked
Red-Green Color Blindness
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Sex-Linked
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
b b
 Only homozygous mutant females (X X ) are
colorblind
 Heterozygous females (XBXb) are asymptomatic
carriers
Sex-Linked
Red-Green
Colorblindness
Chart
Sex-Linked
X-Linked
Recessive
Pedigree
Muscular Dystrophy
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Sex-Linked
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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
Hemophilia
Sex-Linked
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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
Sex-Linked
Fragile X Syndrome
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Sex-Linked
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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
Incomplete Dominance
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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
Incomplete Dominance
Example of
incomplete
dominance:
Snapdragons!
Figure 11.14
Incomplete Dominance
Assessment of dominance depends on
the level of analysis!
Incomplete Dominance
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
Incomplete Dominance
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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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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Co- Dominance
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RBCs sickle
shaped
Anemia
Pain
Stroke
Leg ulcers
Jaundice
Gall stones
Spleen, kidney
& lungs
Sickle cell anemia
http://www.netwellness.org/ency/imagepages/12
Sickle Cell Anemia
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Normal red blood cells
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Co- Dominance
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Hemoglobin S red blood cells (different form of hemoglobin A)
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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 than 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
Multiple Alleles
•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
Multiple Alleles
Multiple Alleles
Immunology 101
(In a nutshell)
Multiple Alleles
•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
Multiple Alleles
Multiple Alleles
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
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!
Multiple Alleles
Polygenic Inheritance
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Polygenic Interitance
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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
additive effects (essentially, incomplete dominance) of
multiple genes on a single trait (phenotypic appearance)
Polygenic Interitance
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.
Polygenic Interitance
Polygenic Interitance
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?
Polygenic Interitance
Pleiotropy
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From the Greek words
meaning “many” and
“influences”
A single gene
influences more than
one characteristic
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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).
Pleiotropy
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.
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always linked, again
showing the complexity
of genetic interactions in
determining phenotypes.
A Comparison
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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Epistasis
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BbEe X BbEe
Set up this cross and determine the
ratios of the offspring
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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
Epistasis
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.
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
Environmental Influences
Temperature can affect gene
expression!
Let’s Experiment
Environmental Influences
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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
Environmental Influences
Himalayan rabbits… why go black in the cold?
Temperature
Environmental Influences
Environmental Influences
Effect of temperature
on pigment expression in Siamese cats
Burrrrrr
It’s getting hot in
here….
Environmental Influences
Even diet can make a difference!
Where’s
the beef?
Caterpillar fed Oak flowers
Caterpillar fed Oak leaves
Environmental Influences
Got Air?
More Mostly Human
Genetics
Chromosome Number: Polyploidy
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Polyploidy
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Human Genetics
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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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Human Genetics
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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)
Human Genetics
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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
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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
Human Genetics
Trisomy 21
a.k.a. Down’s Syndrome
Human Genetics
Chromosome Number:
Abnormal Sex Chromosome Number
Human Genetics
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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
Human Genetics
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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
Human Genetics
Chromosome Number:
Abnormal Sex Chromosome Number
Human Genetics
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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
Deletion
Missing segment of chromosome
Lost during breakage
Duplication
Human Genetics
A segment of a chromosome is
repeated in the same chromosome
Inversion
Occurs as a result of two
breaks in a chromosome
The internal segment is
reversed before re-insertion
Genes occur in reverse order in
inverted segment
Translocation
A segment from one
chromosome moves to a nonhomologous chromosome
Follows breakage of two
nonhomologous chromosomes
and improper re-assembly
Abnormal Chromosome Structure
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Deletion Syndromes
Human Genetics
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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
Human Genetics
Williams Syndrome
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Human Genetics
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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
Human Genetics
Alagille Syndrome
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Human Genetics
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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…