Cat caryotype (38 chromosomes)

dihybrid

d → dilute pigment

L → short hair – dominant l → long hair

The Calico phenotype reflects transcriptional

regulation by chromatin structure

specifically X chromosome inactivation

-Cat Genetics and Mosaicism

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 !

XIC

Chromosome counting mechanism: when 2 or more XIC are present, X inactivation takes place

MOSAICISM in

♀

Barr bodies.

M. Lyon (hypothesis)

→

Tortoise shell &

Calico cats.

Can calico cats be clonally produced ?

Euchromatic configuration

Etherochromatic configuration

Xist = X inactive specific transcript

encodes a non translated RNA (18 Kb)

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

X_m maternal X_p 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:

Also in mice and rabbits

Probably related to the ability to camouflage

A coat pattern in which each individual hair has light-colored bands contrasted with

darker-colored bands. The lighter color lies close to the skin and the hair ends with a dark tip.

Agouti = yellow/orange bands

ALL CATS, regardless of color, are

genetically tabbies carrying:

T

wild type (Mackerel or striped) or

T

_{(Abyssinian or ticked or agouti) or}

t

_{(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.

Wild type T

Tabby Black cat

Genotype: aa B C D L T(?)

t

_T

Basic pattern of stripes

T

-ticked

T

_T

_{or Tt}

striped

t

_t

classic

ss

SS

The S allele is incompletely dominant, but variably expressed

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 = full

color

dominant gene

c

₌

_{recessive Siamese gene}

c

₌

_{recessive Burmese gene}

c

= albino (very rare)

c

_{is only partially dominant over c}

Human Blood type ABO is inherited in a

codominant pattern – 4 types

-H-antigen ( )

Oligosaccharide moiety of glycolipids exposed on the

surface of human red blood cells

A B H

dominant dominant

recessive

Cytogenetic band of ABO gene: 9q34.1-q34.2

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

Transferase A, alpha 1-3-N-acetylgalactosaminyltransferase; Transferase B, alpha1-3-galactosyltransferase;

AB

I

_I

B

I

_I

_{& I}

_I

A

I

_I

_{& I}

_I

O

I

_I

Blood type

Genotype

Distribution of the B type blood allele

Distribution of the O type blood allele Distribution of the A type blood allele

The distribution of blood groups differ around the world

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.

CAT GENETICS and

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.

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.

aa

= non-agouti

B

= black pigment

C = maximum pigmentation

D = dense pigmentation

ii

= full development of pigmentation

S =

white spotting

Magpie cats: aa B C D ii S Magpie is the name given to the pattern

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)

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.

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

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 + → for a warm or deep color Polygenes Rufus - → for a cool or pale coat color

Growth within the womb

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

Environmental effects on gene

expression

T-effect on c

_c

_{(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}

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.

EPISTATIC EFFECT

PLEIOTROPY

LETHAL GENES

CAT GENETICS and …

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}

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.

1 15 A epistatic to B or b B epistatic to A or a (duplicate dominant epistasis) 7 9 aa epistatic to B or b bb epistatic to A or a (duplicate recessive epistasis) 1 3 12 A epistatic to B or b (dominant epistasis) 4 3 9 aa epistatic to B or b (recessive epistasis) 1 3 3 9

A&B both dominant (typical dihybrid) 1 3 2 1 6 3 A intermediate, B dominant 1 2 1 2 1 4 2 2 1 A&B both intermediate

aabb aaBb aaBB Aabb AAbb AaBb AaBB AABb AABB GENOTYPES

Pleiotropic effects

(already observed by Mendel)

with lack of anthocyanin

“a single gene influences more than one phenotype”

in cats:

c

_c

_{(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

Lethal Genes

Pleiotropic effects

-Ay _{lethal yellow mutation was described in 1905.} Heterozigosity leads to obesity, increased tumor susceptibility and premature infertility.

[Deviation from

Merc = Maternally expressed hnRNP C-related gene Essential for pre-implantation of the embryo

Lethal Genes

Manx (M allele) → Mm → short or missing tail

→ MM → lethal during gestation

→ mm → normal tail

Lethal genes can upset the typical Mendelian phenotypes ratio [ 2:1 instead of 3:1 ]

Tailless Manx cat

Can they land on their feet?