Cat caryotype (38 chromosomes)

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1 CAT GENETICS

2 Cat caryotype (38 chromosomes)

3 D Dense pigment d dilute pigment L short hair dominant l long hair monohybrid dihybrid

4 Cat Genetics and Mosaicism The Calico phenotype reflects transcriptional regulation by chromatin structure - specifically X chromosome inactivation - Oo heterozygous

5 1 X chromosome MAMMALS 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)

6 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

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8 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?

9 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!!

10 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

11 Summary of the dosage-compensation and X-chromosome inactivation strategies X m maternal X p paternal

12 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)

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14 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 = yellow/orange bands Non-agouti = no yellow/orange bands

15 ALL CATS, regardless of color, are genetically tabbies carrying: T T a t b 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.

16 t b Wild type T T a ticked Basic pattern of stripes Tabby Black cat Genotype: aa B C D L T(?)

17 T a - ticked T m T m or Tt b striped t b t b classic

18 The S allele is incompletely dominant, but variably expressed continuous gradient of white pigmentation ss SS

19 CAT GENETICS and CODOMINANCE

20 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 S = recessive Siamese gene c b = recessive Burmese gene c a = albino (very rare) c b is only partially dominant over c S Dominance series (or hierarchy) : C > c b = c s > c a > c

21 Human Blood type ABO is inherited in a codominant pattern 4 types - H-antigen ( ) dominant dominant recessive Oligosaccharide moiety of glycolipids exposed on the surface of human red blood cells A B H Universal recipient

22 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

23 Neither gene is dominant over the other I o I o Genotype Blood type O I A I A I B I B I A I B & I A I o & I B I o A B AB

24 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

25 CAT GENETICS and INCOMPLETE DOMINANCE

26 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. c b c s = Tonkinese combination phenotype

27 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.

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29 Magpie cats: aa B C D ii S Magpie is the name given to the pattern aa B C D ii S = non-agouti = black pigment = maximum pigmentation = dense pigmentation = full development of pigmentation = white spotting

30 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)

31 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.

32 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

33 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

34 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

35 Melanin (a derivative of tyrosine) is the black pigment giving rise to black color polymer 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

36 Environmental effects on gene expression T-effect on c S c S (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

37 Primary colours in CAT

38 The figure illustrates that skin color in humansisa 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.

39 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.

40 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.

41 CAT GENETICS and EPISTATIC EFFECT PLEIOTROPY LETHAL GENES

42 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 Epistasis should not be confused with dominance, which refers to the interaction of genes at the same locus.

43 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 whitetovariableextent] in WW degeneration of inner ear (cochlea) Deafness (mainly in blue-eyed white cats) careless mothers in ww normal pigmentation

44 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.

45 MODIFICATIONS OF THE DIHYBRID RATIO GENOTYPES AABB AABb AaBB AaBb AAbb Aabb aabb aabb aabb A&B both intermediate A intermediate, B dominant A&B both dominant (typical dihybrid) aa epistatic to B or b (recessive epistasis) A epistatic to B or b (dominant epistasis) aa epistatic to B or b bb epistatic to A or a (duplicate recessive epistasis) 9 7 A epistatic to B or b B epistatic to A or a (duplicate dominant epistasis) 15 1

46 Pleiotropic effects (already observed by Mendel) with lack of anthocyanin a single gene influences more than one phenotype in cats: c S c S (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

47

48 Pleiotropy A gene Anthocyanin production a gene NO Anthocyanin production

49 Lethal Genes - Pleiotropic effects - [Deviation from Mendelian proportion] A y lethal yellow mutation was described in Heterozigosity leads to obesity, increased tumor susceptibility and premature infertility.

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

51 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?

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