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UNIVERSITY OF VETERINARY MEDICINE - BUDAPEST

DEPARTMENT OF ANIMAL BREEDING NUTRITION AND LABORATORY

ANIMAL SCIENCE

SECTION FOR ANIMAL BREEDING AND GENETICS

Gene effects, Mendelian exceptions

László Zöldág prof. emer.

Mendel’s laws in simple inheritance (for monogenic

traits!)

Preconditions: monogenic, single locus, location on different chromosomes, not X-linked!

1. Homozygosity of parents

• 2. Uniformity and reciprocity (criss-cross) in F1 generation: – identity of genotype and phenotype in case of homozygous

parents,

– independently which of parents carries the dominant or the recessive genes.

• 3. Segregation in F2 generation (1:2:1, 3:1): reappearance of parental characteristics in F2 generation

• 4. Independent and free segregation and new combinations of genes at diff. loci (9:3:3:1 segregation in case of two loci): inter-chromosomal or Mendelian recombination in mono-, di-, tri- and polyhybrid crossings.

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Exceptions for Mendelian Rules: Terminology

• Varied expressivity of dominant genes (white spotting and grey

colour in horses, epigenetics)

• Incomplete penetrance of dominant genes (%, canine JKD)

• Multiple alleles, allelic polymorphism (on the same locus)

• Epistasis (interlocal interaction of genes, coat colours - oligogenie)

– Complementary or epistatic oligogenie (comb types of fowl,

coat colours)

• Genetic heterogeneity (mimic genes, diff. genotypes the same

phenotype)

• Linkage and crossing over (intrachromosomale recombination)

• Pleiotropy (dosage effect or linkage, „side” effects of genes,

Polledness in goats, lethal genes, FecX in sheep)

• Sex-X(Z)-linked inheritance (sexing, auto-sexing chicks, X-linked

diseases)

• Uniparental inheritance (genomic imprinting, maternal inheritance –

mtDNA)

Changes in gene effects: Mendelian inheritance is

not true (?)

• Expressivity of genes:

– Varied manifestation of dominant genes in heterozygotes, and recessive genes in homozygotes.

– Varying expression of the same gene in individual phenotype is possible.

• Explanation: mRNA transcription and translation (transcription factors, epigenetics).

• By chance phenomenon: migration of melanocytes during embryonic development.

– Examples: grey colour in horses, white colour

and white spotting in more species (horses and

dogs).

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Grey-horses (G-, varying expressivity with age)

Flea bitten (Lipizzan)

Dapple grey

(Hung. Sporthorse)

„White” horse (Shagya) Thoroughbred-Arab

Tobiano and Overo white

spotting (varying expressivity of

dominant gene in Paint/Pinto horse

breeds:

Tobiano homozygote/heterozygote

(To/To; To/to)

Overo homozygote/heterozygote

(O/O; O/o)

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Varying gene-expressivity of white (p, piebald)

spotting in dogs

(English Bulldog, Landseer, Pyrenean Shepherd, The

same genotype: spsp)

Epigenetics

• Epigenetics, epigenomics: changes, modifications to DNA in gene expression and transcriptions. Not DNA-based inheritance:

– Transcription factors.

– (miRNA).

– Influence of cytoplasmatic factors on nuclear DNA • DNA-methylation, acetylation,

• histone modifications and associations to DNA,

• cell memory.

– Individual and transgenerational inheritance and environmental effects: acquired characteristics (not DNA-based) can be inherited through cell memory for 2-3 generations.

– X-chromosome inactivation, maternal effects, environmental effects (nutrition)

– Genomic imprinting (uniparental inheritance): gene inactivation, gene silencing: regulation, switching on and off of gene expressions in gametes.

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Changes in gene effects: Mendelian inheritance is

not true (?)

• Penetrance of genes:

– Differences of the dominant gene in

heterozygotes.

– Penetrance may be complete

(100%) or

– Incomplete (?%), percentage at

population level.

– Example: JKD, juvenile kidney

disease of dogs, histology positive,

clinical signs only 5-10%).

Dominance with incomplete penetrance

(Example: JRG, Juvenile Renal Dysplasia

in dogs)

• Many breeds of dogs are affected with JRD, common phenotype: characterized by immature glomeruli, and/or tubules.

• Penetrance refers to the population frequency that the phenotype (or some characteristics of the disease) is observed.

• If, for example, the penetrance is 75%, then the chances of offspring to develop a disease are 3 out of 4.

• In the case of JRD, the penetrance is low. – Estimated to be about 2-5% (max 10%).

– Therefore only a small number of individuals with the mutation will show clinical signs of the disease.

• However, they can pass the disease on to their offspring (dominance!).

• This is why a genetic test is crucial to manage JRD; this is the only way to eliminate this disorder.

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Changes in gene effects: Mendelian inheritance is

not true (?)

• Multiple alleles, allelic series, allelic variants =

polymorphism on the same locus; serial genes –

allelic variants in order of dominance or co-dominant

inheritance.

– One pair (gene – allele) in an organism (on

homologous chromosomes).

– Increase of combinations in populations.

– Examples: colour inheritance, albinism (alleles: C,

cch , ch, cb, c), blood group systems, MHC

haplotypes etc.)

– SNP (single nucleotide polymorphism = point

mutation): very common sort of multiple alleles.

Genotype (DNA) polymorphism

(more allelic variants on the same locus at

population level)

• Prerequisite for variability and diversity of populations!

• General feature of genome and individuals, detectable:

– In genotype: chromosome structures and molecular level (genes, alleles, microsatellites etc) and

– in phenotype: colour, biochemical constituents, proteins and enzymes, blood groups.

• Co-dominant inheritance: blood groups, proteins, enzymes.

• Gene/allele (coding DNA sequences): polymorphic systems based frequently on SNP (single nucleotide polymorphism = point mutations).

• Microsatellites (not coding, inactive DNA sequences): polymorphism on different number of repeating units.

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Polymorphic „c” alleles of C-locus

(tyrosinase), allelic series in

dominance hierarchy in rabbits:

C: normal pigment synthesis

cch: chinchilla

ch=cs: Himalayan, Siamese,

colourpoint California rabbits (heat

sensitive tyrosinase, OCA2)

cb: blue-eyed albinism

c: true or red-eyed albinism (OCA1)

OCA = oculocutaneous albinism

Polymorphic „c” alleles of C-locus

(tyrosinase), allelic series in

dominance order in cats:

C: normal pigment synthesis (tabby)

ch=cs: Himalayan, Siamese,

colourpoint cats (heat sensitive

tyrosinase, OCA2)

cb: blue-eyed albinism

c: true or red-eyed albinism (OCA1)

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Alleles and genotypes of locus C: cch, cs (=ch), cb, c.

(heat sensitive tyrosinase variants, colourpoints, Siamese,

Himalayan cats, Albinism)

cscs, Siamese

cscs, Himalayan

cc: red-eyed

albino

• Allelic polymorphism and varying gene

expression (in age, pups are born dark!)

• A (agouti, agouti signaling protein, ASIP):

polymorphic alleles, dominance hierarchy:

Ay > Aw or A+> at > a. Colours: DNA-test.

– Ay, fawn/sable (yellowish, reddish, darker tips),

– aw or a+: wild, wolf colour, pale grey, banded;

– at: black and tan, tan points; saddle or blanket; at at

or ata

– aa: only recessive black (Shetland Sheepdog and

German Shepherd).

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Phenotype polymorphism (gene products, proteins)

• Colour inheritance: in a single locus more than two allelic variants, polyallelism, allelic or gene polymorphism (agouti and albino locus, tyrosinase mutations)

• Blood groups: blood group systems (in a system more than two alleles or factors)

• Biochemical (protein and enzyme) polymorphic systems: albumin, transferrin, lactoferrin, alpha-, beta- and kappa-caseins, LDH, GPX etc.

• MHC (major histocompatibility complex, immunsystem, HLA, LA, human leukocyte antigen, BLA, bovine): linked groups/units of polymorphic genes, haplotypes, inherited as „single gene or locus” – MHC class I: β2-microglobulins,

– MHC class II: B-lymphocytes and macrophage’s histoglobulins, presentation of antigens to T-lymphocytes,

– MHC class III: complements, heat shock proteins, TNF: tumour necrosis factor

Changes in gene effects: Mendelian inheritance is

not true (?)

• Epistasis (modifiers): epistatic/hypostatic

relation of genes at different loci (interlocal

interaction of genes) frequently at coat

colours (oligogenie).

• Epistasis - complementary or epistatic oligogenie:

comb types of fowl, coat colours e.g.

– Combless (bdbd),

– Combed (BdBd, Bredas fowl breed):

• rose (R),

• pea (P),

• walnut (R-P-) and

• simple (rrpp) comb

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Epistatic relation (interlocal interaction) between three gene

loci (grey, G, agouti, A, and extension- melanokortin receptor, E)

• Epistasis (modifiers): epistatic/hypostatic relation of genes at

different loci (interlocal interaction of genes) frequently at

coat colours (e.g. grey colour of horses, G)

Interlocal

interactions:

G- and A-/aa locus

G- and E-/ee locus A-/G-/E- ee/G- aa/G-/E-

Varied gene expressivity of grey colour:

territorial/ age (dapple grey, flea bitten grey)

Complementary or epistatic oligogenie: comb types and forms

of fowl: loci included: combed (Bd) from Bredas breed; rose (R),

pea (P), walnut (R-P-) and simple (rrpp) comb. Possible genotypes (3

gene loci included),

allelic combinations: Combless: bdbd

Combed: BdBd

rose (BdBd; R-/pp),

walnut (BdBd; R-/P-),

pea (BdBd; rr/P-),

simple (BdBd; rr/pp).

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Changes in gene effects: Mendelian inheritance is

not true (?)

• Genetic heterogeneity (mimic genes, different

genotypes - the same or similar phenotype):

– frequently at genetic diseases (COL, collagen

diseases - dermatosparaxis, PRA, progressive retinal

atrophy of dogs, colours etc).

– Mutations on different gene loci the same or

similar clinical entity (phenotype), or

– different mutations on the same gene locus (allelic

variants) the same or different phenotypes,

clinical entity.

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Genetic heterogeneity (heterogenia)

(different genotypes - allelic variations and mutations –

similar phenotype, mimicry phenomenon)

• Two kinds of red, black and

grey colour (grey – silver –

blue): different genotypes:

– „Ay” agouti fawn and „ee”

yellow (red);

– Dominant (KB-//B-) and

recessive black (aa);

– Grey (G-, Silver) and „blue”

(dd) kutyák.

Example for genetic heterogeneity of diseases:

dermatosparaxis

• Ehlers-Danlos syndrome (dermatosparaxis or

cutaneous asthenia, HERDA, hereditary equine regional

dermal asthenia, hyperelastosis cutis, HC) in animals.

– Abnormal types of collagen polypeptide.

– Signs: very fragile, tensile, stretching skin, lacerations

(collagen disease).

– Inheritance:

• AR: sheep, cattle (enzyme mutations).

• AD: horse, cat, dog, mink, rabbit (pro-collagen

mutations).

– Difficult to establish the form of inheritance, signs are

similar or the same!

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Dermatosparaxis (hyperelastosis cutis, HC, heterogeneity)

1-, 2-pro-

collagen,

COL1

gene

Collagen,

Connective

tissue

Budapest, 1888 Horse: HERDA,

hereditary equine

regional dermal

asthenia

Pro-collagen 1,

Carboxy-

proteinase

Pro-collagen 2,

Amino-

proteinase

Proteinase

enzymes 1, 2 Winged cats

White colour in horses ( KIT and other gene mutations

(polymorphic alleles, genetic heterogeneity, varying

expressivity and penetrance)

• True (completely) white horses

(majority is Kit gene (tirosin kinase

receptor) mutation, more than 10!)

– Dominant white (W-, Kit,

pleiotropy, homozygote is lethal,

dosage effect)

– White born Appaloosa foal

(LP//LP remains white as adult!)

– Lethal white overo foal

syndrome (EDNRB, endothelin-B

receptor mutation, OO

homozygote is lethal, linkage of

AR mutation)

– Sabino white (sabino-1, SB//SB,

high expression differences )

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Heterogenia (genetic heterogeneity): ichthyosis –

fish scale-disease (hyperkeratosis) in dogs

• Varying phenotype, expression and penetrance

problems.

• Mild or severe keratinisation, hyperkeratosis (Genetic

mutations in 20% of clinical cases).

• Cause: more and different mutations (fat metabolism and

keratin types, ICHTYN, PNPLA1, KRT10, transglutaminase 1

- TGM1).

• More dog breeds are affected (Golden Retriever,

Rhodesian Ridgeback, GSD, Jack Russell Terrier, American

Bulldog and other breeds and crossings).

• Severe puppy cases: euthanasia.

• Mild cases (local scaling): therapy and remission.

Heterogenia (genetic heterogeneity): ichthyosis –

fish scale-disease (hyperkeratosis)

• Due to secondary infections (bacteria, fungi) confusing

clinics!

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Changes in gene effects: Mendelian inheritance is not true (?)

• Linkage and crossing over: close and remote genes on the same chromosome can be linked or exchanged. Results new genetic combinations by intra-chromosomal re-combinations!

• Crossing over: Exchange of remote genes between homologous chromosomes in first meiotic division (AB, ab ↔ Ab, aB) occurs frequently. – Can be utilized in relative positioning of genes

and mapping. Unit of gene distance: 1cM (To date: bp, in base pairs!)

– In swine: Ha blood antigen and stress sensitivity;

– in fowl: linkage of F (frizzled) and I (white plumage) genes;

– linkage groups (MHC haplotypes);

– cat: white coat and deafness;

– rabbit: hair length and solid colour etc.

Double crossing over of linked traits

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Crossing over: segregation of closely linked traits

(recombinations, F-I, frizzle and white); double crossing over

(M-m exchange)

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Changes in gene effects: Mendelian inheritance is

not true (?)

• Pleiotropy as a contradictory term!

• Pleiotropy: phenomenon where a gene affects more than one phenotype (several different traits).

• Background may be linkage or dosage effect.

• Antagonistic pleiotropy: where a gene has a

positive effect on one trait but a negative effect

on another trait (example: dominant lethal genes)

• Pleiotropic lethal genes: the gene causes certain

colour of the coat (or any other trait) and also

affects the viability (lethality).

Pleiotropy in animal genetics

• Classic examples of pleiotropy:

– In humans the disease phenylketonuria (PKU). This

disease can cause mental retardation and reduced hair and

skin pigmentation as pleiotropic effect.

– Deafness in white and blue-eyed cats and dogs.

• Pleiotropy (mainly an „undesired negative side effect” of dominant genes in homozygote).

– Polledness in goats: Polled homozygous (PP) female goats are intersexes and a proportion of males are sterile (may be X-liked mutation).

– X-linked prolificacy gene (FecX) in sheep (prolificacy – infertility /sterility in homozygote ewe, negative dosage effect).

– Dominant lethal genes (dosage effect, colour – vitality/mortality in homozygote)

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Pleiotropy (linkage of deafness and white

colour) in white cats and dogs

Pleiotropy (polledness): Polled homozygous (PP) female goats are intersexes and a proportion of males are sterile

Sex influenced

expression in

Dorset sheep

Both sexes are fertile

in sheep, Vendeen, F,

no pleiotropy)

Pleiotropy is

only in goats!

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Pleiotropy in horses

Grey horses: melanomatosis in homozygote (G//G) with

ageing and depigmentation in skin (vitiligo, pleiotropy).

Appaloosa and other paint horses: dominant leopard

spotting in homozygote (Lp//Lp) may have pleiotropic effect:

ophthalmologic disorders, CSNB (congenital stationary night

blindness) and uveitis (linkage of a recessive mutation)

Fecundity – X-linked fertility gene mutation in sheep - FecX:

BMP15 (bone morphogenetic protein), GDF9B (growth

differentiation factor)

• Sex-limited – sex determined trait:

• Effect only in heterozygotes: superiority of heterozygotes (twinning).

• Dominant inheritance and negative dosage effect: in homozygous ewes ovarian sterility (infertile, FSH – inhibin modulation) - pleiotropy!

• How to breed for it? Crossing with hemizygote rams (XFECY × XfecXfec → XFECXfec)!

• Polymorphism (min. 5 working allelic mutations) – Romney, Inverdale sheep breeds: FecXI

– Irish Belclare, Galway, Hanna sheep breeds: FecXB FecXG FecXH

– Coopworth, Woodland: FecX2W maternal genomic imprinting

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Particular dominant (pleiotropic) lethal genes in animal

breeding

• Field-mouse (wild-agouti colour) yellow mutation (a+aY / a+aY aYaY embryonic lethal)

• Hairlessness in Mexican and Peruvian dogs (HH lethal)

• Manx factor in cats (MxMx lethal)

• Chondrodysplasia in Munchkin cats (MkMk lethal)

• Merle gene mutation in dogs (MM subvital, Mm = merle colour)

• Silver fox platinum colour mutant (WP WP embryonic lethal)

• Silver fox "white face" mutant (W1W1 embryonic lethal, W1WP

also)

• Horse dominant white colour (WW embryonic lethal)

• LWO (lethal white overo foals) of paint/pinto horses (linkage, megacolon = aganglionosis = Hirschsprung-disease, OO lethal postnatal)

• Dexter cattle (Kerry mutant, DD lethal „bulldog” calve)

• Shiraz gene mutation (gray Karakul lamb, ShSh lethal after weaning)

Field-mouse: wild-agouti colour and yellow mutation (a+aY ˟ a+aY aYaY embryonic lethal)

Hairlessness is breed feature

in Chinese, Peruvian and

Mexican hairless dogs (Hh

HH embryonic lethal)

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Silver fox platinum colour mutant (WWP WP WP embryonic

lethal), and "white face" mutant (WW1 W1W1 embryonic

lethal, W1WP also)

Manx factor (Mxmx MxMx lethal) and chondrodysplasia

(Munchkin) (MkMk lethal) in cats

Merle gene mutation in dogs (MM subvital, Mm = merle colour)

Dominant white colour of horses (Ww WW embryonic lethal)

LWO (lethal white overo foals, frame overo white spotting) of

paint/pinto horses (linkage, megacolon, aganglionosis,

Hirschsprung-disease, Oo OO lethal only postnatal)

Ww

ToTo

Foal: OO

Mare: Oo

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Shiraz gene mutation: grey (Sh-) Karakul lamb, only homozygotes (Sh/Sh) are lethal after weaning, due to dysfunction of the rumen)

Dexter (dwarf) cattle (Kerry

mutant, Dd DD lethal

„bulldog” calve)

Genotype: Dd

DD

Changes in gene effects: Mendelian inheritance is

not true (?)

• X(Z)-linked inheritance: uniformity, reciprocity and segregation rules are limitedly true.

• Uniparental inheritance: – Genomic imprinting: gene inactivation,

methylization in one of the sexes during gametogenesis

– Maternal inheritance: mitochondrion, mtDNA, mitochondrion diseases

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SEX DETERMINATION

• Sex chromosomes

– Mammals: XX, XY;

– birds: ZZ, ZW;

– sex ration 50%, homo- and heterogametic males and

females, haploid sex in honey bee and other insects

• Sex (gender) may be: genetic, gonadic, phenotypical,

behavioural

• Sex determination (SD): may be genetic (genotype, sex

chromosomes, GSD, CSD) and environmental (temperature,

TSD)

– Male sex is determined by Y-linked SRY-gene (sex-

determining region on Y-chromosome)

– Female sex: General principle is female sexual

development! XX are needed! Complications may be:

freemartins, intersexes, tfm-syndrome, Turner disease etc.

Genetic (genotype, sex chromosomes, GSD, CSD) and environmental (temperature,

TSD) sex determination in vertebrates

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TSD sex determination by regulating of gene expression: P450

cytochrome aromatase (inhibition or stimulation) (crocodiles,

some lizards, turtles and fishes)

Regulation key: Aromatase activity higher at higher, lower at lower temperature!

DNA sex DNA test in monomorph birds

M: male

F: female

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SEX-LINKED INHERITANCE

• Sex (chromosome)-linked inheritance (XLD XLR, YL) and traits

– Y(W) chromosome rarely inherits (hairy ears in man)

– X(Z) chromosomes may transmit many traits

– Uniformity, reciprocity and segregations (Mendelian rules) are only limitedly true

• Sex-limited inheritance and traits: manifestation only in one of the sexes (inherited by both sexes), milk and egg production, prolificacy, kryptorchismus, white heifer disease in shorthorn cattle

• Sex influenced inheritance and traits: expression in both sexes but differently, meat production, muscling, racing performance, horns in Dorset sheep etc.

X-linked inheritance in mammals

Tortoiseshell or tortie (bicolour, tricolour, calico) female cats (XOXo):

Also called as X-inactivation in female Mammals.

Gene dosage compensation (X-inactivation) between male and female sexes.

O dominant red allele is X–linked inherited only in cats.

Appear two colours: red + another colour in females!

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Only in female Mammals: By chance

50-50 % of maternal and paternal X-

chromosomes are inactivated in

somatic cells (during embryonic

development).

Importance for understanding the

pathophysiology of X-linked dominant

diseases (less severe in females!)

X-linked inheritance of red (O, orange) colour

in cats: tortoiseshell or tortie females

• O (orange, epistatic dominant): X-linked, XL inheritance, due to 50-50% X-inactivation or gene dosis compensation → heterozygote female cats are tortoiseshell, alleles O-, oo, and genotypes:

– XOXo: tortoiseshell or tortie females (Oo), due to X-inactivation, maternal and paternal X-chromosomes in embryonic cells are randomly (up to 50-50 %) inactivated (bi-colour);

– XoXo: any colour;

– XOY hemizygous males: red;

– XoY hemizygous males: any not red colour;

– XXY (trisomia, Klinefelter syndrome) or mozaics (XX/XY), rarely chimeras: rare tortie male!

– Oo and S- combination is called a calico (tri-coloured cat)

Spackled

paw, mottling)

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X-linked inheritance in mammals: X-linked diseases

•Recessive mutations:

•In mammals males (XdY), in birds females (ZdW) are affected!

•Always the hemizygote and the heterogametic sex is

severely diseased!

•Dominant mutations:

•The hemizygote is always severely diseased!

•Females (heterozygote, XDXd) are less severely diseased.

•Due to X-inactivation (maternal and paternal up to 50-50%).

•Examples: •Hemophilia A (VIII) and B (IX) in dog (recessive males: XhY).

•Duchenne Muscular dystrophy (DMD, dystrophin, XmdY): Golden

Retriever, Belgian Sheepdog.

•Nephritis (X-linked recessive and dominant): Samoyed, Spaniel.

•Tremor (recessive, shaker disease, myoclonia): hypomyelinogenesis,

Spaniel.

•Severe combined immunodeficiency (SCID, X-linked recessive)

•Antimasculine and antifeminine lethal genes in mammals and fowl.

Use of Z-linked inheritance for detecting sex

of day-old chicks: sexing

• Phenotype sexing (cloacal eminence)

• Feather colour and feathering (feather growth) genes are Z-linked, in criss-cross inheritance: F1 is not uniform!

• Breeding homozygous lines first! (males are homozygous recessive, females dominant hemizygotes in crossings)

• Genes for sexing fowl

– Silver dominant (S-) and gold (ss) feather: Rhode island red males (ZsZs) × Sussex or Wyandotte white females (ZSW): F1 will be different in colour: ZSZs ; ZsW

– Slow dominant (K) and rapid, fast (kk) feathering in chickens: fast ZkZk males × slow ZKW females: F1 will be different in feather growth: ZKZk ; ZkW

– Barred, barring (B-) and black (bb) feather colour: Rhode island black males (ZbZb) × barred Plymouth females (ZBW): F1 will be different in colour: ZBZb; ZbW

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Black and barring criss-cross

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Dosis effect in Z-linked inheritance: auto-

sexing character (colour-sex links)

• Auto-sexing character: homo- and heterogametic sexes (homo- and hemizygotes) are different in colour due to dosage effect

• In genetically pure, homozygous lines in young and adult age!

• Auto-sexing genes: – pigmentation inhibitor gene (II, I-) in Texan

and King pigeons (homogametic males are lighter)

– Barring (BB, B-) in chickens (homogametic males are lighter)

– Grey (sd, sdsd) feather of geese (homogametic males are lighter colour, „white”, Pilgrim goose)

• To distinguish from sex dimorphism!

Auto-sexing breeds: Plymouth,

Welbar, Gold Legbar

Day old chicks

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Use of Z-linked inheritance to produce uniform F1 generation

• Uniformity of F1 in both sexes: if males are homozygous dominant in crossings

• Dwarf poultry (dwarfism): Z-linked recessive gene (dw), intensive growth is dominant, regulates GH receptors and growth

– Practical application in broiler chicken production (dwarf, dw homozygous maternal lines are more economical!)

– Crossing: dwarf females (ZdwW) × intensive growth males (ZDwZDw)→ F1 will be intensive growth (ZDwZdw ,

ZDwW)

– ZdwW × ZDWZDW → F1 uniform: ZDWZdw , ZDWW both sexes of F1!

Normal growth line Dwarf line

Both sexes are of

intensive growth

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Use of Z-linked inheritance to produce uniform F1 generation

• Uniformity of F1 in both sexes: if males are homozygous dominant in crossings!

• To produce white feather in geese (white is important):

– White feather (silver dilution, Sd) of geese is dominant, grey colour (wild, sd) is recessive.

– Crossing dominant white (SdSd) males × grey females (sd-) → F1 (Sdsd, Sd-) can be used for white feather production.

– ZSdZSd × Zsd-→ F1 uniform: ZSdZsd, ZSd-, both sexes are! white

Uniparental inheritance

• Expression in both sexes and only

one of parents inherits!

• 1. Genomic imprinting, gene

inactivation maternal or paternal: 3

genotype (allelic) variations

(callipyge, muscular hypertrophy

dominant gene of sheep):

– CLPGP - activated during spermatogenesis

and expressed in somatic cells

– clpg - no mutated gene

– CLPGM - inactivation during oogenesis and

not expressed in somatic cells

• 2. Maternal inheritance: mitochondrion

diseases (to distinguish maternal

effects!)

Callipyge (CLPG)

muscular

hypertrophy in sheep

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Maternal (mitochondrion) inheritance

Genomic imprinting (= gene inactivation)

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Maternal effect =

complex: genetic

(genome: nucleus

+ mitochondrion)

and

environmental

components.

Classical (historical)

experiments:

1. Pony × shire horse crossing

(polygene, the same genome!)

2. Transfer of black and adipose

mouse embryos in white mice

(sigle gene)

Don’t be confused about maternal effect and maternal inheritance!

Mare Mare Stallion Stallion

Birth

1 Month

Exceptions for Mendelian Rules: Summary

• Varied expressivity of dominant genes (coat colours, epigenetics)

• Incomplete penetrance of dominant genes (%, canine JKD)

• Multiple alleles, allelic polymorphism (very common)

• Epistasis (interlocal interaction of genes, coat colours)

• Complementary or epistatic oligogenie (comb types of fowl,

colours)

• Genetic heterogeneity (mimic genes, diff. genotypes the same

phenotype)

• Linkage and crossing over (intrachromosomale recombination)

• Pleiotropy (dosage effect, „side” effects of genes, Polledness in

goats, lethal genes, FecX in sheep)

• Sex-X(Z)-linked inheritance (sexing, auto-sexing chicks, X-

dosage compensation in mammals)

• Uniparental inheritance (genomic imprinting, maternal

inheritance – mtDNA)