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Tyrosinase‑related protein 2 (TRP‑2) is one of the most important members of the tyrosinase family, and is a key enzyme involved in melanin biosynthesis. In the present study, a skin transcriptome profile, immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction were used to investigate TRP‑2 expression in sheep with different coat colors, namely, black, white and black‑white. TRP‑2 was overexpressed in melanocytes in order to study the effect of TRP‑2 on melanin production. Results revealed differing TRP‑2 levels in sheep of different coat colors and in various parts of the coat with different colors in the same sheep. TRP‑2 expression levels in dark‑colored areas were significantly increased compared with light‑colored areas in piebald sheep. TRP‑2 overexpression may regulate melanogenesis and significantly increase melanogenesis associated transcription factor expression in vitro. Therefore, TRP‑2 may affect melanin production in sheep, and different expression levels determine coat color. The results may provide novel approaches for developing therapeutic strategies for skin diseases associated with pigmentation disorders.

Merle is a distinct coat color and pattern found in numerous species, including the domestic dog, characterized by patches of diluted eumelanin (black pigment) interspersed among areas of normal pigmentation. In dogs, this variegated pattern is caused by an insertion of a SINE element into the canine PMEL gene. Although variation in the length of the SINE insertion - due to a variable-length poly(A) tail - has been observed to be associated with variation in merle coat color and patterning, no systematic evaluation of this correlation has been conducted and published in the scientific literature. We performed high-resolution analysis of the SINE insertion lengths in 175 dogs (99 Australian shepherds, 45 miniature Australian shepherds, and 31 miniature American shepherds) and compared the genotypes with the coat phenotypes (when available). SINE insertion lengths varied from 201 to 277 bp, indicating that merle insertion variants can occur in virtually any size along the entire continuum. Genotype-phenotype correlation of 126 dogs with only a single SINE insertion (m/M) identified at least 4 major phenotypic clusters designated as "cryptic," "atypical," "classic," and "harlequin" merle. However, we found several phenotypic outliers that did not cluster within these major groupings, suggesting that insertion size is not the only factor responsible for merle phenotypic variability. In addition, we detected 25 dogs with 2 SINE insertions (M/M) and 24 dogs with more than 2 PMEL (merle) alleles, indicating mosaicism. Genotype-phenotype correlation of M/M dogs suggests that cryptic merle alleles often act like non-merle (m) alleles when combined with atypical, classic, and harlequin-sized alleles. The finding of mosaicism has important implications for the dog's phenotype and the ability to potentially transmit various alleles to its offspring. Furthermore, we identified examples of the SINE insertion poly(A)-tail expansion and contraction between generations, which also has important implications for breeding practices and determining mating pairs to avoid producing double merle dogs. These data demonstrate that there is a continuum of merle insertion lengths associated with a spectrum of coat color and patterns and that genotype-phenotype exceptions and overlap make it difficult to strictly assign certain insertion sizes with an expected coat color, although some generalizations are possible., (© 2018 S. Karger AG, Basel.)

Background: Studies on the molecular genetics of horse skin pigmentation have typically focused on very few genes and proteins. In this study, we used Illumina sequencing to determine the global gene expression profiles in horses with white-colored coats and those with black-colored coats, with the goal of identifying novel genes that could regulate horse coat color., Results: Genes encoding ribosomal-associated proteins were highly expressed in horse skin. We found a total of 231 unigenes that were differentially expressed between horses with white coats and horses with black coats; 119 were down-regulated, and 112 were up-regulated. Many of the up-regulated genes in black horses, such as genes related to tyrosine metabolism, may directly regulate dark coat color. Keratin genes, MIA family genes, fatty acid-related genes, and melanoma-associated genes were also differentially regulated, which suggests that they may play important roles in coat color formation., Conclusions: These findings show that the transcription profiles from white and black horse skin provide useful information to understand the genetics underlying the control of skin melanin synthesis in horses, which may enhance our knowledge of human skin diseases, such as melanoma and albinism.

The effects of the use of glyphosate (GLY), glyphosate plus carfentrazone (GLY/CAR), and paraquat (PAR) as plant desiccators on the technological and chemical properties of cowpea grains were investigated. All studied desiccants provided lower cooking time to freshly harvested cowpea. However, the coat color of PAR- and GLY/CAR-treated cowpea was reddish in comparison to the control treatment. Principal component analysis (PCA) from liquid chromatography-mass spectrometry (LC-MS) data sets showed a clear distinction among cowpea from the different treatments. Catechin-3-glucoside and epicatechin significantly contributed for discriminating GLY-treated cowpea, while citric acid was responsible for discriminating GLY/CAR-treated cowpea. Quercetin derivative and gluconic acid were responsible for discriminating control treatment. Residual glyphosate and paraquat content was higher than the maximum limits allowed by Codex Alimentarius and the European Union Commission. Improvements in the technological and chemical properties of cowpea may not be overlapped by the risks that those desiccants exhibit when exceeding the maximum limits of tolerance in food.

The Burmese is a breed of domestic cat that originated in Southeast Asia and was further developed in the United States. Variants in melanocortin 1 receptor (MC1R) causes common coat colour phenotypes in a variety of mammalian species but only limited colour variation in the domestic cat. Known as the extension (E) locus, melanocortin 1 receptor (MC1R) interacts with the agouti locus to produce the eumelanin and pheomelanin pigments. Recently, a novel reddish coloration, which is termed russet, was identified in the Burmese cat breed. Because this russet Burmese coloration changes with aging, MC1R was suggested as candidate gene. The similar colouration in specific lineages of Norwegian Forest cat known as amber (e) (c.250G>A; p.Asp84Asn) was excluded for this Burmese phenotype. The complete 954-bp coding region of MC1R was directly sequenced in russet Burmese and suspected carriers. A 3-bp deletion (c.439_441del) associated with the deletion of a phenyalanine (p.Phe146del) in the protein sequence was identified. All russet coloured cats were homozygous for the variant, and all obligate carriers were heterozygous, confirming that the deletion segregated concordantly with colouring in Burmese cats from the New Zealand foundation lineage. The variant was not identified in 442 cats from 26 different breeds and random-bred cats. Twenty-six Burmese from the USA did not have the variant. This MC1R variant defines a unique coloration and the second breed-specific MC1R variant in cats. The interactions of the two recessive feline MC1R alleles (E  >  e, e r ) is unknown., (© 2016 Stichting International Foundation for Animal Genetics.)

The deleterious effects of heat stress on animal health are being increasingly recognized. This study aimed to determine hair cortisol (HC) and serotonin levels in lactating Holstein cows under heat stress conditions with different coat and hair-cut color. Forty-five multiparous lactating Holstein cows (days in milk = 130 ± 47, body weight = 753 ± 85 kg) were divided to two main groups of over 80% black coat color (BC) and over 85% white coat color (WC) visually observed based on registry certificates and subdividing to black hair sample (BH) and white hair samples (WH) in 2 × 2 factorial arrangements. Hair samples were taken from the forehead of the individuals. Higher HC levels were observed in BC than WC cows (P < 0.05). No differences were found in HC levels between BH and WH groups (P > 0.05). Serotonin levels showed no difference between BC and WC (P > 0.05). Interaction between coat color and hair color was not significant (P > 0.05). The cortisol levels in hair are not affected by pigmentation. However, pigmentation within the coat alters cortisol levels. In conclusion, white coat color retains less cortisol than the black coat. Therefore, white coats are preferable for dairy cows under heat stress conditions., (© 2016 Japanese Society of Animal Science.)

Horses have substantial variation in coat color, and the genetic loci responsible for the coat color variations have been well investigated. It has been believed that some color variations should follow a single-locus Mendelian law. Examples include the Gray locus that causes the gray phenotype and the Extension locus that specifies the chestnut phenotype. We reevaluated the roles of the Gray and Extension loci by using a large number of mating records of Thoroughbred racing horses. We showed that the data indeed fits the Mendelian law extremely well for the two loci. Furthermore, we demonstrated that the Extension and Agouti loci might have an additional role in determining the degree of melanin that should distinguish bay, dark bay, and brown.

Guanine nucleotide-binding protein subunit alpha-s (Gnαs) is a small subunit of the G protein-couple signaling pathway, which is involved in the formation of coat color. The expression level and distribution of Gnαs were detected by quantitative real-time-polymerase chain reaction (qPCR), western blot, and immunohistochemistry to investigate the underlying mechanisms of coat color in white and black skin tissues of mice. qPCR and western blot results suggested that Gnαs was expressed at significantly higher levels in black mice compared with that of white mice, and transcripts and protein possessed the same expression in both colors. Immunohistochemistry demonstrated Gnαs staining in the root sheath and dermal papilla in hair follicle of mice skins. The results indicated that the Gnαs gene was expressed in both white and black skin tissues, and the expression level of Gnαs in the two types of color was different. Therefore, Gnαs may be involved in the coat color formation in mice.

To investigate whether ocular albinism type 1 ( OA1 ) is differentially expressed in the skin of mice with different coat colors and to determine its correlation with coat color establishment in mouse, the expression patterns and tissue distribution characterization of OA1 in the skin of mice with different coat colors were qualitatively and quantitatively analyzed by real-time quantitative PCR (qRT-PCR), immunofluorescence staining and Western blot. The qRT-PCR analysis revealed that OA1 mRNA was expressed in all mice skin samples tested, with the highest expression level in brown skin, a moderate expression level in black skin and the lowest expression level in gray skin. Positive OA1 protein bands were also detected in all skin samples by Western blot analysis. The relative expression levels of OA1 protein in both black and brown skin were significantly higher than that in gray skin, but there was no significant difference between black and brown mice. Immunofluorescence assays revealed that OA1 was mainly expressed in the hair follicle matrix, the inner and outer root sheath in the skin tissues with different coat colors. To get further insight into the important role of OA1 in the melanocytes' pigmentation, we transfected the OA1 into mouse melanocytes and then detected the relative expression levels of pigmentation-related gene. Simultaneously, we tested the melanin content of melanocytes. As a result, the overexpression of OA1 significantly increased the expression levels of microphthalmia-associated transcription factor ( MITF ), tyrosinase ( TYR ), tyrosinase-related protein 1 ( TRP1 ) and premelanosome protein ( PMEL ). However, the tyrosinase-related protein 2 ( TRP2 ) level was attenuated. By contrast, the level of glycoprotein non-metastatic melanoma protein b ( GPNMB ) was unaffected by OA1 overexpression. Furthermore, we observed a significant increase in melanin content in mouse melanocyte transfected OA1 . Therefore, we propose that OA1 may participate in the formation of coat color by regulating the level of MITF and the number, size, motility and maturation of melanosome., Competing Interests: The authors declare no conflict of interest.

The melanocortin-1 receptor (MC1R) belongs to the family of seven transmembrane G protein-coupled receptors and plays a central role in animal coat color. We have sequenced the full coding region of 954bp of the MC1R gene in 72 goats of three breeds with different coat colors and identified five missense mutations (K226E, F250V, G255D, V265I, and C267W) and one silent mutation (A61A), among which two haplotypes with complete linkage disequilibrium (A61A and F250V, G255D and V265I) were found. We performed detailed functional studies on the six single and two double mutations in transiently transfected HEK293T cells. We found that none of the mutants had decreased cell surface expression. However, all the mutants except A61A had decreased constitutive activities in the cAMP pathway. Five mutations (F250V, G255D, G267W, A61A/F250V, G255D/V265I) exhibited significant defects in ligand binding and consequent agonist-induced cAMP signaling and ERK1/2 activation. Additionally, K226E, with normal ligand binding affinity and cAMP signaling, showed a significant defect in ERK1/2 activation, exhibiting biased signaling. Co-expression studies showed that the five defective mutants did not affect wild-type MC1R signaling, hence they were not dominant negative. In summary, we provided detailed data of these goat MC1R mutations leading to a better understanding of the role of MC1R mutation and coat color in goats., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Yung-Chih Lai, Shiao-Wei Huang, and Hon-Tsen Yu (2016) Color polymorphism is a long-standing issue in ecological and evolutionary biology. The black-bellied vole ( Eothenomys melanogaster ) with complete melanic and brown forms provides an outstanding opportunity to study the genetic polymorphism underpinning color variation. Mutations in the coding region of melanocortin 1 receptor ( Mc1r ) have been shown to cause color variation in a wide range of species. However, the contribution to color variation produced by the Mc1r regulatory regions have rarely been studied in wild animals. To this end, the Mc1r promoter sequence in black-bellied voles was cloned and characterized in this study. At least 11 distinct transcription initiation sites were identified using 5'-RACE. Furthermore, a candidate core promoter region in the upstream GC-rich sequence was identified based on key transcription factor binding motifs. The black-bellied vole Mc1r coding region was conserved with that found in the house mouse and demonstrated characteristics that are consistent with the structure of a G-protein coupled receptor, e.g. seven transmembrane domains. We found a negative association between coat color variations and polymorphisms of either regulatory or coding regions. This implies that Mc1r might reflect geographic cline rather than adaptive evolution. Although we found a negative association, the extra information we obtained in the Mc1r promoter of the black-bellied vole can be beneficial to other studies in exploring the association between regulatory mutations and adaptive phenotypes in wild animals.

Guanine nucleotide-binding protein subunit alpha-s (Gnαs) and guanine nucleotide-binding protein subunit alpha-11 (Gnα11) play an important role in coat color formation. To improve our understanding of Gnαs and Gnα11 expression levels and pattern in the skin of black sheep (Ovis aries) compared with white sheep, we analyzed the expression levels through quantitative real time PCR (qPCR) and Western blot, immunohistochemistry and immunofluorescence. qPCR and Western blot results suggested that Gnαs and Gnα11 were significantly expressed at high levels in black sheep skin compared with the white sheep skin. Gnα11 expression was higher than Gnαs expression in both skin colors, transcripts and protein exhibited the same expression pattern in white and black sheep skins. Immunohistochemical results revealed that Gnαs and Gnα11 were localized in the outer root sheath of hair follicle in sheep. Furthermore, the expression of Gnα11 in outer root sheath of hair follicle was stronger than that in Gnαs. Immunofluorescencence further demonstrated that signals of Gnαs and Gnα11 were detected in outer root sheath and hair papilla. These results provide a novel insight into the role of Gnαs and Gnα11 in the regulation of sheep coat color., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Melanocortin receptor 1 (MC1R), Agouti signaling protein (ASIP), and Tyrosinase-related protein 1 (TYRP1) are reported critical genes that regulate pheomelanin and eumelanin synthesis in mammals. Liangshan pig is a special Chinese indigenous pig breed with two completely different coat colors, solid black and blond. In this study, we detected polymorphisms of the above three genes and assessed the relationships between the variations and coat color phenotypes in Liangshan pigs. The findings revealed that the blond phenotype of Liangshan pig was related to dominant mutations in TYRP1, but not related to mutations in MC1R or ASIP. We found three closely linked mutations in TYRP1, g.8406G>A in intron 4, g.11100A>G in intron 5, and g.17599&#95;17604del in exon 8, that were completely associated with blond coat color in Liangshan pigs. Further analysis revealed that a 6-bp deletion mutation resulted in deletion of Met and Gly residues at positions 495 and 496 in TYRP1 protein, and altered the structure of transmembrane domain of TYRP1. Together, our findings indicated that these three mutations in TYRP1 cause the blond phenotype in Liangshan pigs., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Domestication and subsequent selective pressures have produced a large variety of pig coat colors in different regions and breeds. The melanocortin 1 receptor (MC1R) gene plays a crucial role in determining coat color of mammals. Here, we investigated genetic diversity and selection at the coding region of the porcine melanocortin receptor 1 (MC1R) in Tibetan pigs and Landrace pigs. By contrast, genetic variability was much lower in Landrace pigs than in Tibetan pigs. Meanwhile, haplotype analysis showed that Tibetan pigs possessed shared haplotypes, suggesting a possibility of recent introgression event by way of crossbreeding with neighboring domestic pigs or shared ancestral polymorphism. Additionally, we detected positive selection at the MC1R in both Tibetan pigs and Landrace pigs through the dN/dS analysis. These findings suggested that novel phenotypic change (dark coat color) caused by novel mutations may help Tibetan pigs against intensive solar ultraviolet (UV) radiation and camouflage in wild environment, whereas white coat color in Landrace were intentionally selected by human after domestication. Furthermore, both the phylogenetic analysis and the network analysis provided clues that MC1R in Asian and European wild boars may have initially experienced different selective pressures, and MC1R alleles diversified in modern domesticated pigs., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The authors explored a possible relationship between coat color and aggressive behaviors in the domestic cat. This study used an Internet-based survey to collect information on coat color, affiliative behaviors toward cats/humans, agonistic behaviors toward cats/humans, other "problem" behaviors, and cat and guardian demographic data. A total of 1,432 cat guardians completed the online survey; after exclusions based on study protocol, data analysis included 1,274 completed surveys. Guardians reported sex-linked orange female (tortoiseshells, calicos, and "torbies"), black-and-white, and gray-and-white cats to be more frequently aggressive toward humans in 3 settings: during everyday interactions, during handling, and during veterinary visits. Kruskal-Wallis 1-way analysis of variance was used to compare possible differences between the 2 sexes and among different coat colors. Analyses of aggression due to handling, as well as aggression displayed during veterinarian visits, showed little difference among coat colors in these settings.

Introduction: To investigate whether the membrane-associated transporter protein SLC45A2 is differentially expressed in the skin of sheep with different coat colors and to determine its correlation with coat color establishment in sheep., Material and Methods: The expression of SLC45A2 in sheep skin samples with different coat colors was qualitatively and quantitatively analyzed by PCR amplification, RT-PCR, immunohistochemical staining and Western blotting., Results: A 193-bp SLC45A2 CDS sequence was successfully amplified from sheep skin samples with diverse coat colors. RT-PCR analysis revealed that SLC45A2 mRNA was expressed in all sheep skin samples tested, with relative expression levels of 512.74 ± 121.51 in black skin, 143.38 ± 119.31 and 1.36 ± 0.09 in black dots and white dots of piebald skin, respectively, and 1.02 ± 0.23 in white skin (p < 0.01**). Positive SLC45A2 protein bands were also detected in all skin samples by Western blot analysis, with relative expression levels of 0.85 ± ± 0.17** in black skin, 0.60 ± 0.05** and 0.34 ± 0.07 in black dots and white dots of piebald skin, respectively, and 0.20 ± 0.05 in white skin (p < 0.01**). Immunohistochemical assays revealed that SLC45A2 was expressed in the hair follicle matrix, the inner and outer root sheath, and the dermal papilla in the skin tissues with different coat colors. These patterns were quantified by optical density (OD) analysis, which yielded relative expression levels of 0.23 ± 0.11 in black skin, 0.19 ± 0.09 and 0.10 ± 0.03 in black dots and white dots of piebald skin, respectively, and 0.08 ± 0.01 in white skin (p < 0.05*)., Conclusion: SLC45A2 is detectably expressed in sheep skin of all coat colors, though at significantly different levels. SLC45A2 may participate in the establishment of coat color by regulating the synthesis and trafficking of melanin.

Hepatocyte growth factor (HGF)/c-Met signaling has been considered as a key pathway in both melanocyte development and melanogenesis. To understand better the expression patterns and tissue distribution characterization of HGF and its receptor c-Met in skin of white versus brown alpaca (Vicugna pacos), we detected the tissue distribution of HGF and c-Met using immunohistochemistry and analyzed the expression patterns by using Western blot and quantitative real time PCR (qPCR). Immunohistochemistry analysis demonstrated that HGF staining robustly increased in the dermal papilla and mesenchymal cells of white alpaca skin compared with that of brown. However, c-Met staining showed strongly positive result, particularly inhair matrix and root sheath in brown alpaca skin. Western blot and qPCR results suggested that HGF and c-Met were expressed at significantly high levels in white and brown alpaca skins, respectively, and protein and transcripts possessed the same expression pattern in white and brown alpaca skins. The results suggested that HGF/c-Met signaling functions in alpaca coat color formation offer essential theoretical basis for further exploration of the role of HGF/c-Met signaling in pigment formation., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

The red fox (Vulpes vulpes) demonstrates a variety of coat colors including platinum, a common phenotype maintained in farm-bred fox populations. Foxes heterozygous for the platinum allele have a light silver coat and extensive white spotting, whereas homozygosity is embryonic lethal. Two KIT transcripts were identified in skin cDNA from platinum foxes. The long transcript was identical to the KIT transcript of silver foxes, whereas the short transcript, which lacks exon 17, was specific to platinum. The KIT gene has several copies in the fox genome: an autosomal copy on chromosome 2 and additional copies on the B chromosomes. To identify the platinum-specific KIT sequence, the genomes of one platinum and one silver fox were sequenced. A single nucleotide polymorphism (SNP) was identified at the first nucleotide of KIT intron 17 in the platinum fox. In platinum foxes, the A allele of the SNP disrupts the donor splice site and causes exon 17, which is part of a segment that encodes a conserved tyrosine kinase domain, to be skipped. Complete cosegregation of the A allele with the platinum phenotype was confirmed by linkage mapping (LOD 25.59). All genotyped farm-bred platinum foxes from Russia and the US were heterozygous for the SNP (A/G), whereas foxes with different coat colors were homozygous for the G allele. Identification of the platinum mutation suggests that other fox white-spotting phenotypes, which are allelic to platinum, would also be caused by mutations in the KIT gene., (© 2015 Stichting International Foundation for Animal Genetics.)

Agouti Signaling Protein (ASIP) controls the localized expression of red and black pigment in the domestic dog through interaction with other genes, such as Melanocortin 1 Receptor and Beta-Defensin 103. Specific ASIP alleles are necessary for many of the coat color patterns, such as black-and-tan and saddle tan. Mutations in 2 ASIP alleles, ay and a, have previously been identified. Here, we characterize a mutation consisting of a short interspersed nuclear element (SINE) insertion in intron 1 of ASIP that allows for the differentiation of the aw wolf sable and at black-and-tan alleles. The SINE insertion is present in dogs with the at and a alleles but absent from dogs with the aw and ay alleles. Dogs with the saddle tan phenotype were all at/at. Schnauzers were all aw/aw. Genotypes of 201 dogs of 35 breeds suggest that there are only 4 ASIP alleles, as opposed to the 5 or 6 predicted in previous literature. These data demonstrate that the dominance hierarchy of ASIP is ay > aw > at > a. [ABSTRACT FROM PUBLISHER]

Wild boar meat cannot be easily distinguished from domestic pig meat, especially in processed products, thus it can be fraudulently substituted with cheaper domestic pork. In this study we genotyped polymorphisms in two genes (MC1R, affecting coat color and NR6A1, associated with number of vertebrae) in 293 domestic pigs of five commercial breeds, 111 wild boars sampled in Italy, and 90 in Slovenia and other Western Balkan regions. Allele and genotype frequency data were used to set up a DNA-based method to distinguish meat of wild boars and domestic pigs. Genotyping results indicated that domesticated genes were introgressed into wild boar populations. This complicated the determination of the origin of the meat and would cause a high error rate if markers of only one gene were used. The combined use of polymorphisms in the two analyzed genes substantially reduced false negative results., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

White-spotting patterns in mammals can be caused by mutations in the gene KIT, whose protein is necessary for the normal migration and survival of melanocytes from the neural crest. The alpaca (Vicugna pacos) blue-eyed white (BEW) phenotype is characterized by 2 blue eyes and a solid white coat over the whole body. Breeders hypothesize that the BEW phenotype in alpacas is caused by the combination of the gene causing gray fleece and a white-spotting gene. We performed an association study using KIT flanking and intragenic markers with 40 unrelated alpacas, of which 17 were BEW. Two microsatellite alleles at KIT-related markers were significantly associated (P < 0.0001) with the BEW phenotype (bew1 and bew2). In a larger cohort of 171 related individuals, we identify an abundance of an allele (bew1) in gray animals and the occurrence of bew2 homozygotes that are solid white with pigmented eyes. Association tests accounting for population structure and familial relatedness are consistent with a proposed model where these alleles are in linkage disequilibrium with a mutation or mutations that contribute to the BEW phenotype and to individual differences in fleece color., (© The American Genetic Association. 2012. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Domestic yaks (Bos grunniens) exhibit two major coat color variations: a brown vs. wild-type black pigmentation and a white spotting vs. wild-type solid color pattern. The genetic basis for these variations in color and distribution remains largely unknown and may be complicated by a breeding history involving hybridization between yaks and cattle. Here, we investigated 92 domestic yaks from China using a candidate gene approach. Sequence variations in MC1R, PMEL and TYRP1 were surveyed in brown yaks; TYRP1 was unassociated with the coloration and excluded. Recessive mutations from MC1R, or p.Gln34*, p.Met73Leu and possibly p.Arg142Pro, are reported in bovids for the first time and accounted for approximately 40% of the brown yaks in this study. The remaining 60% of brown individuals correlated with a cattle-derived deletion mutation from PMEL (p.Leu18del) in a dominant manner. Degrees of white spotting found in yaks vary from color sidedness and white face, to completely white. After examining the candidate gene KIT, we suggest that color-sided and all-white yaks are caused by the serial translations of KIT (Cs6 or Cs29 ) as reported for cattle. The white-faced phenotype in yaks is associated with the KIT haplotype S(wf) . All KIT mutations underlying the serial phenotypes of white spotting in yaks are identical to those in cattle, indicating that cattle are the likely source of white spotting in yaks. Our results reveal the complex genetic origins of domestic yak coat color as either native in yaks through evolution and domestication or as introduced from cattle through interspecific hybridization., (© 2014 Stichting International Foundation for Animal Genetics.)

The site 1 protease, encoded by Mbtps1, mediates the initial cleavage of site 2 protease substrates, including sterol regulatory element binding proteins and CREB/ATF transcription factors. We demonstrate that a hypomorphic mutation of Mbtps1 called woodrat (wrt) caused hypocholesterolemia, as well as progressive hypopigmentation of the coat, that appears to be mechanistically unrelated. Hypopigmentation was rescued by transgenic expression of wild-type Mbtps1, and reciprocal grafting studies showed that normal pigmentation depended upon both cell-intrinsic or paracrine factors, as well as factors that act systemically, both of which are lacking in wrt homozygotes. Mbtps1 exhibited a maternal-zygotic effect characterized by fully penetrant embryonic lethality of maternal-zygotic wrt mutant offspring and partial embryonic lethality (~40%) of zygotic wrt mutant offspring. Mbtps1 is one of two maternal-zygotic effect genes identified in mammals to date. It functions nonredundantly in pigmentation and embryogenesis.