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Transcript
CAT GENETICS
Cat caryotype (38 chromosomes)
D → Dense pigment
monohybrid
d → dilute pigment
L → short hair – dominant
l→
long hair
dihybrid
Cat Genetics and Mosaicism
The Calico phenotype reflects transcriptional
regulation by chromatin structure specifically X chromosome inactivation -
Oo heterozygous
♂
MAMMALS
1 X chromosome
♀
2 X chromosomes → Do females have twice
the level of gene products than males?
Answer: NO!
because of GENE DOSAGE COMPENSATION
Inactivation of one of the two X
chromosomes. Barr body
– Murray Barr analysis of neural
cells from female cats (1949)
One of the two X chromosomes condenses into
facultative heterochromatin.
Genes on the Barr body are not transcribed
50 % cells inactivate paternal X
50 % cells inactivate maternal X
RANDOMLY !
Chromosome counting mechanism: when 2 or more XIC
are present, X inactivation takes place
XIC
Developmental signals
Euchromatic configuration
Etherochromatic configuration
Xist = X inactive specific transcript
encodes a non translated RNA (18 Kb)
MOSAICISM in ♀
Barr bodies.
M. Lyon (hypothesis) → Tortoise shell &
Calico cats.
Can calico cats be clonally produced ?
What about Hemophilia (F8C gene) ?
Hereditary genetic disorder
(recessive X-linked) that
impairs the body’s ability to
control blood clotting or
coagulation.
Transfusions performed in the ’70s and ’80s led to HIV
and Hepatitis C Virus (HCV) infections!!
Drosophila
Both X chromosomes are active, but transcriptional
“adjustment” ensures the same level of expression
in X and XX.
Up-regulation of the genes present in the single
X-chromosome through chromatin loosening;
Down-regulation of the XX genes through chromatin
tightening
Summary of the dosage-compensation
and X-chromosome inactivation strategies
Xm maternal
Xp paternal
O
X-linked allele
O = blocks the expression of other colors
→ orange
o = allows other colors → generally black
S = white spotting
Female Calico cats: Oo S aa B C D ii
Male cats are hemizygous:
either O (orange) or o (black)
A coat pattern in which each individual hair has
light-colored bands contrasted with darkercolored bands. The lighter color lies close to the
skin and the hair ends with a dark tip.
Also in mice and rabbits
Probably related to the ability to camouflage
Agouti
=
Non-agouti =
yellow/orange bands
no yellow/orange bands
ALL CATS, regardless of color, are
genetically tabbies carrying:
T
Ta
tb
wild type (Mackerel or striped) or
(Abyssinian or ticked or agouti) or
(blotched or classic)
Tabby is not a colour;
it is a coat pattern with distinctive features
(stripes or dots), usually together with an
"M" mark on the forehead.
tb
Wild type T
Ta
ticked
Basic pattern of stripes
Tabby Black cat
Genotype: aa B C D L T(?)
Ta-
TmTm or Ttb
tbtb
ticked
striped
classic
The S allele is incompletely dominant, but variably expressed
→
continuous gradient of white pigmentation
ss
SS
CAT GENETICS and
CODOMINANCE
Co-dominance and Dominance series
With codominance, a cross between organisms with two different
phenotypes produces offspring with a third phenotype in which both
of the parental traits appear together.
C
cS
cb
ca
=
=
=
=
full color dominant gene
recessive Siamese gene
recessive Burmese gene
albino (very rare)
cb is only partially dominant over cS
Dominance series (or hierarchy) : C > cb = cs > ca > c
Human Blood type ABO is inherited in a
codominant pattern – 4 types -
dominant
H-antigen
(
dominant
)
recessive
Oligosaccharide moiety of
glycolipids exposed on the
surface of human red blood cells
A
B
H
Universal recipient
Cytogenetic band of ABO gene: 9q34.1-q34.2
Transferase A, alpha 1-3-N-acetylgalactosaminyltransferase;
Transferase B, alpha1-3-galactosyltransferase;
O phenotype results from a frameshift mutation.
Rh factor is a trasmembrane protein –
2 genes located on Chr.1 1p36.13-p34.3
Rh+ individuals: genotype RHD dominant (DD or Dd) →
production of D antigen;
Rh- individuals: genotype RHd recessive (dd) → no
antigen
> 30 possible combinations due to different epitopes
Neither gene is dominant over the other
Genotype
Blood type
Io Io
O
IA IA & IA Io
A
IB IB & IB Io
B
IA IB
AB
The distribution of blood groups differ around the world
Distribution of the A type blood allele
Distribution of the B type blood allele
Blood type AB is the rarest of
the blood groups.
It is most common in Japan,
regions of China, and in Koreans,
being present in about 10% of
these populations.
Distribution of the O type blood allele
CAT GENETICS and
INCOMPLETE DOMINANCE
With incomplete dominance,
a cross between organisms
with two different phenotypes
produces offspring with a third
phenotype that is a blending of
the parental traits.
cbcs = Tonkinese – combination phenotype
Incomplete Dominance
The alleles for curly hair and straight hair are
examples of alleles for a trait that are
codominant.
Individuals with curly hair are homozygous for
curly hair alleles.
Individuals with straight hair are homozygous
for straight hair alleles.
Individuals who are heterozygous, with one of
each allele have wavy hair, which is a blend of
the expressions of the curly and straight hair
alleles.
Magpie cats: aa B C D ii S
Magpie is the name given to
the pattern
aa
= non-agouti
B
= black pigment
C
= maximum pigmentation
D
= dense pigmentation
ii
= full development of pigmentation
S
= white spotting
Variation of gene expression
(i.e. ≠ phenotypes) as a result of:
Modifier genes (or polygenes)
e.g. “rufus” polygenes → modification of
orange phenotype in OO
Growth within the womb
e.g. Oo → different types of
tortoiseshell (orange & black patchwork)
Environmental effects (e.g. Siamese points)
Single genes determine whether or not the coat will be agouti
and which tabby pattern the coat will show.
What determines the quality (deep, warm or on the
contrary pale, cool, etc.) of the color or the quality of
the coat pattern (clearly or vaguely defined)?
All these various smoothly flowing gra-dations of color and
pattern cannot be caused continually by a different single gene
for each one of them.
The cause of all these gradations is called: polygenes
(or modifiers).
Polygenes follow the same genetic laws as single
genes, but in a continuous, flowing variation without
limits that can be defined with any precision and this
because it concerns so many genes at the same time
that exert their influence in the same direction.
Modifier genes (or polygenes)
modification of orange phenotype in genotipically OO cats
The polygenes for the quality of the coat color are called
"Rufus polygenes", they determine whether the coat is
fawn or apricot.
Polygenes Rufus +
Polygenes Rufus -
→
→
for a warm or deep color
for a cool or pale coat color
Growth within the womb e.g. Oo → different
types of tortoiseshell (patchwork of orange and black)
Which X is inactivated (i.e. that carrying O or o) is
stochastic so that different patterns of patchwork
arise
Tortoiseshell is theoretically impossible in males
which, being XY, are either O (red) or o (non-red).
However, there are rare XXY sterile males which
are Oo Tortoiseshell
Melanin (a derivative of
tyrosine) is the black pigment
giving rise to black color
Almost all other colors are due to
a) genetic modifications of this pigment
or
b) to the way in which this pigment
is laid down in hair fibers
polymer
Environmental effects on gene
expression
T-effect on cScS (Siamese) diminished
amount of pigment in hair and iris of eyes
In Siamese cats there is little pigment
in body hair and more in points where T
is lower because the amount of pigment produced
depends upon Temperature
- ts mutant, tyrosinase T high → low amount of pigment
T low → high amount of pigment
Primary colours in CAT
The figure illustrates that skin color in
humans is a quantitative character.
Quantitative characters usually indicate
that the character is controlled by more
than one gene
polygenic inheritance
A simplification of the genetics of skin
color in humans shows that three genes
interact to determine the level of
pigment in an individual's skin (actually
there are > 10 genes involved in the
production of melanin).
The dominant alleles (A, B, and C) each
contribute one "unit" of pigment to the
individual, and their effects are
cumulative, such that individuals with
more of these alleles will be darker
than those with fewer alleles.
The recessive alleles (a, b, and c) do not contribute any units
of pigment.
Therefore, skin color is related to the number of dominant
alleles present in each individual's genotype.
A cross of two completely heterozygous parents produces
SEVEN genotypes in their offspring, ranging from very
light to very dark skin.
The distribution of skin color in the offspring would
resemble a bell-shaped curve because there would be
more individuals with intermediate skin colors than either
extreme.
As the number of genes involved increases, the
differences between the various genotypes become more
subtle and the distribution fits the curve more closely.
Quantitative Genetics
Polygenic inheritance, also known as
quantitative or multifactorial inheritance
refers to inheritance of a phenotypic characteristic
(trait = QTL) that can be attributed to two or more
genes, or the interaction of genes with the
environment, or both.
Other examples of polygenic inheritance in humans
include height, hair color, eye color (≠ expression of
melanin) and body mass.
This helps to explain the slight variations in these
characters that we see in different individuals.
CAT GENETICS and …
EPISTATIC EFFECT
PLEIOTROPY
LETHAL GENES
Epistasis: When the expression of one
gene interferes with the expression of
another gene.
Such genes are called inhibiting genes.
First defined by the English geneticist
William Bateson in 1907.
Epistasis should not be confused with
dominance, which refers to the interaction
of genes at the same locus.
W allele (white dominant) does NOT code for
the “white colour”, but masks the expression of
all other color genes. W cats are all White.
EPISTATIC EFFECT
[Note that SS and Ss cats have patches of
white to variable extent]
in WW → degeneration of inner ear (cochlea)
→ Deafness (mainly in blue-eyed white cats)
→ careless mothers
in ww → normal pigmentation
Two epistatic recessive genes can
produce deaf-mutism in humans
A , B → Normal Hearing
a , b → Deaf-Mutism
Homozygotic condition for either of these two
(recessive) genes causes deafness and mutism
Two persons with normal hearing,
heterozygous for both of these genes, may
have both normal children and deaf-mutes in
the ratio of 9 : 7
This ratio can be worked out by the
checkerboard method.
MODIFICATIONS OF THE DIHYBRID RATIO
AABB
AABb
AaBB
AaBb
AAbb
Aabb
aaBB
aaBb
aabb
2
4
1
2
1
2
1
1
2
GENOTYPES
A&B both intermediate
A intermediate,
B dominant
1
2
3
6
A&B both dominant
(typical dihybrid)
9
3
aa epistatic to B or b
(recessive epistasis)
9
3
A epistatic to B or b
(dominant epistasis)
aa epistatic to B or b
bb epistatic to A or a
(duplicate recessive
epistasis)
A epistatic to B or b
B epistatic to A or a
(duplicate dominant
epistasis)
1
3
1
4
12
9
3
3
1
7
15
1
Pleiotropic effects (already observed by Mendel)
with lack of anthocyanin
“a single gene influences more than one phenotype”
in cats:
cScS (light sepia-brown pigment) → abnormalities in
the optic nerve
→ Faulty connection between brain and eyes
→ Reduced 3D vision
→ Some (mostly Siamese) cats develop a squint to
compensate for double vision
Pleiotropy
A gene
a gene
Anthocyanin
production
NO
Anthocyanin
production
Lethal Genes - Pleiotropic effects -
[Deviation from
Mendelian proportion]
Ay lethal yellow mutation was described in 1905.
Heterozigosity leads to obesity, increased tumor
susceptibility and premature infertility.
Merc = Maternally expressed hnRNP C-related gene
Essential for pre-implantation of the embryo
Lethal Genes
Manx (M allele) → Mm →
→ MM →
→ mm →
short or missing tail
lethal during gestation
normal tail
Lethal genes can upset the typical Mendelian
phenotypes ratio
[ 2:1 instead of 3:1 ]
Spina bifida
Tailless Manx cat
Can they land on their feet?