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The topic of today's lecture is Coat color genetics in farm animals.

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The lecture is part of Module 2: Animal genetics, that is a part of the ISAGREED project.

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This presentation was supported by Erasmus+ KA2 Cooperation Partnerships Grant

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"Innovation of the content and structure of study programmes

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in the field of management of animal genetic and food resources using digitalization".

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As part of the lecture we will first talk about the importance of coat color and changes in coloration related to domestication.

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Then I will briefly explain pigment synthesis.

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We will list the main genes involved in coat coloration in mammals

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and explain their action using the example of cattle.

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At the end of the lecture, I will mention pleiotropic effect of selected genes.

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There are several important functions of pigment synthesis.

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Coat color is of importance for mating, for protection against predators, and as an adaptation to the environment.

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In fur animals, the coat color is an important production trait.

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In other species such as cattle and sheep, the coat color is an important breed characteristic.

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In contrast to their wild ancestors, domesticated species are often characterized

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by a substantial allelic variability of coat-color-associated genes.

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Recent studies demonstrate that the selection for coat-color phenotypes started at the beginning of domestication.

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Characteristic of modern domesticated animals is their large phenotypic variation,

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which is not found in any of their wild ancestors.

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Wild species are usually uniform in phenotype and show species-specific colors and patterns.

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By contrast, domesticated species are highly variable in both colors and color patterns.

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Although to date more than 300 genetic loci and more than 150 identified coat-color-associated genes have been discovered,

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which influence pigmentation in various ways. Some of them are listed at the right side of this slide.

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In connection with pigmentation, across mammal species, the first two are mainly mentioned,

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the gene for agouti signaling protein (ASIP), and the gene for melanocotin 1 receptor (MC1R).

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These two genes are related to the type of pigment produced and its subsequent distribution on the animal body.

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Several mutations of the KIT gene, which are related to the activity of tyrosinase,

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the important enzyme in the process of pigment formation, are often mentioned in connection

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with the white color, which is often referred to as the "color of domestication". It will be discussed later.

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The process of pigment cell development is crucial for the determination of mammalian coat coloration.

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The pigmentation progress is subdivided into three major stages:

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melanocyte development; pigment production; and pigment distribution.

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Melanocytes can produce the two different pigments

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- eumelanin (dark brownish to black) and pheomelanin (yellowish to reddish).

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This picture shows the process of the formation of pigment cells.

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During vertebrate embryogenesis, neural crest cells arise along the dorsal neural tube,

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and some differentiate into melanoblasts (precursors of melanocytes),

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which migrate ventrally along the body.

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Melanoblasts typically enter the epidermis, where some remain,

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while others localize to the hair follicles and differentiate into melanocytes.

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These melanocytes produce pigment.

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Once pigment is produced, it is packaged into melanosomes

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and transferred to keratinocytes of developing hair (or epidermal cells).

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Melanocytes can produce the two different pigments:

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eumelanin (dark brownish to black) and pheomelanin (yellowish to reddish).

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Tyrosinase is the rate-limiting enzyme in melanogenesis.

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There are over 100 alleles of tyrosinase that have been characterized, ranging from null alleles,

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resulting in the complete absence of pigmentation (so called albinism),

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to alleles with reduced function that limit the melanin production (seen for example in cremello horses).

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Regarding the possible colour phenotypes we distinguish two basic categories.

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On the one hand the so called solid colour, which covers all forms from fully pigmented to white.

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The second group include patterned phenotypes – for example dorso-ventral pigmentation,

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white spotting or markings in varying extents or other special patterns as leopard complex.

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The basic coat color in both categories is given by the ratio between the two types of pigment - eumelanin and pheomelanin.

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This ratio is primarily determined by the agouti signaling protein (ASIP)

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and melanocortin 1 receptor (MC1R) genes mentioned earlier.

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As an example, we will now explain the determination of the formation

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of two different types of pigment and the determination of spotting in cattle.

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In this case, the genotype at two loci, namely EXTENSION and SPOTTING, is important.

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At the EXTENSION locus, three basic alleles have been described in cattle,

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denoted in the genetic notation as usual by uppercase and lowercase letters,

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and since it is an allelic series, we also use the so-called index notation.

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The order of dominance in this series is in the order in which the alleles are listed, therefore from dominant to recessive form.

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The EXTENSION gene determines the pigment color of an animal.

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The dominant allele E is responsible for the production of eumelanin in coat cells of black animals

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and the recessive allele e for phaeomelanin responsible for the red color in animals.

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A third allele is responsible for the wild phenotype (red or red-brown, sometimes  with a light backline).

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It follows from the hierarchy of the alleles that homozygous recessive individuals at the EXTENSION locus are red,

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individuals with at least one dominant allele will be black,

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and carriers of the E+ allele represent the so-called "wild type" phenotype.

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The representation of individual alleles in the population is breed-specific.

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Not all breeds necessarily carry all the listed alleles.

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This also determines what colors we find in the given breed.

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There are breeds uniform in coat color, but also breeds where different color phenotypes are presented.

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The second important locus for coat color in cattle is the SPOTTING locus.

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A total of four alleles are known at this locus.

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The intra-allelic interaction are a bit more complicated resulting in different spotting pattern occuring in cattle.

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There are four alleles recognized at the SPOTTING locus.

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S+ for non-spotting phenotype, SH for Hereford pattern, Sp is responsible for lined back-pattern seen Pinzgauers

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and reccessive allele makes up irregular white spotting seen in breeds like Holstein.

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As a result of pleiotropy (the situation when one gene influences two or more seemingly unrelated phenotypic traits),

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some of the color phenotypes may be associated with the occurrence of defects or diseases.

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For example:

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Oculocutaneous albinism is often connected with vision disorders.

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In horses, in connection with one of the spotting patterns (referred as frame overo),

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the so-called overo lethal white syndrome can appear,

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which is associated with a homozygous dominant genotype at the OVERO locus.

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Affected foals are born after the full 11-month gestation and externally appear normal,

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though they have all-white or nearly all-white coats and blue eyes.

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However, internally, these foals have a nonfunctioning colon.

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Within a few hours, signs of colic appear; affected foals die within a few days.

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Because the death is often painful, such foals are often euthanized once identified.

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In order to prevent the breeding of such an affected foal, it is recommended

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not to mate two carriers of the causative mutation in endothelin receptor type B gene.

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Another disease associated with appaloosa or leopard spotting is night blindness,

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which is more prevalent in homozygous individuals.

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In one of the types of pigment dilution (namely silver one),

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the occurence of multiple congenital ocular anomalies) was described.

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Grey horses are proven to be more susceptible to melanoma's occurrence.

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The positive fact is that these horses usually only develop melanoma at an older age,

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the progression is slower compared to tumors in solid-colored horses,

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and many horses can live with melanoma for a relatively long time without any health complications.

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The merle phenotype is problematic in dogs, where homozygotes

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(so-called double merle) are often deaf and infertile.

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In this context, the International Cynological Federation FCI prohibits the mating of two Merle individuals.

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In this case, the problem may be the so-called cryptic merle, which may not show up in the phenotype.

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Furthermore, some mutations in the KIT gene can negatively affect fertility

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(e.g. in mice or cattle), or may even be lethal (e.g. in horses or hamsters).

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Another manifestation of pleiotropy can be, for example, differences in behavior associated with certain coat color.

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Although the link between tame behavior and coat coloration is not well understood,

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mutations affecting receptor functions could be directly linked to both traits.

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Domestication studies on foxes, rats and minks strongly supported a close relationship

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between the selection for tameness and a manifestation of novel color variants.

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There is a speculated correlation between pale coat color and lower aggressiveness

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related to the common synthesis pathway of adrenalin and dopaquinone from DOPA.

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There are several examples highlighting the correlation between coat color and temperament:

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albinos are less robust,

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horses with the cream allele are gentle and tame,

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piebald cattle, white sheep and swine are more sensitive to certain herbs,

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red Cocker Spaniels are more nervous than other phenotypes of this breed.

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To conclude this presentation:

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Artificial selection is the main factor responsible for the large phenotypic variation observed in domesticated animals.

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Selection for coat color phenotypes started at the beginning of domestication

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resulting in a significant increase of polymorphism in coat-color associated loci.

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The production and ratio of eumelanin and pheomelanin is mainly regulated by the MC1R and ASIP genes.

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Some coat-color phenotypes are associated with or linked to disorders.

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At this moment I would like to thank you for your attention and if you have any questions, you can use the e-mail listed here.