The feather pattern autosomal barring in chicken is strongly associated with segregation at the MC1R locus.

Color patterns within individual feathers are common in birds but little is known about the genetic mechanisms causing such patterns. Here, we investigate the genetic basis for autosomal barring in chicken, a horizontal striping pattern on individual feathers. Using an informative backcross, we demonstrate that the MC1R locus is strongly associated with this phenotype. A deletion at SOX10, underlying the dark brown phenotype on its own, affects the manifestation of the barring pattern. The coding variant L133Q in MC1R is the most likely causal mutation for autosomal barring in this pedigree. Furthermore, a genetic screen across six different breeds showing different patterning phenotypes revealed that the most striking shared characteristics among these breeds were that they all carried the MC1R alleles Birchen or brown. Our data suggest that the presence of activating MC1R mutations enhancing pigment synthesis is an important mechanism underlying pigmentation patterns on individual feathers in chicken. We propose that MC1R and its antagonist ASIP play a critical role for determining within-feather pigmentation patterns in birds by acting as activator and inhibitor possibly in a Turing reaction-diffusion model.

A missense mutation in TYRP1 causes the chocolate plumage color in chicken and alters melanosome structure.

The chocolate plumage color in chickens is due to a sex-linked recessive mutation, choc, which dilutes eumelanin pigmentation. Because TYRP1 is sex-linked in chickens, and TYRP1 mutations determine brown coat color in mammals, TYRP1 appeared as the obvious candidate gene for the choc mutation. By combining gene mapping with gene capture, a complete association was identified between the chocolate phenotype and a missense mutation leading to a His214Asn change in the ZnA zinc-binding domain of the protein. A diagnostic test confirmed complete association by screening 428 non-chocolate chickens of various origins. This is the first TYRP1 mutation described in the chicken. Electron microscopy analysis showed that melanosomes were more numerous in feather follicles of chocolate chickens but exhibited an abnormal structure characterized by a granular content and an irregular shape. A similar altered morphology was observed on melanosomes of another TYRP1 mutant in birds, the roux mutation of the quail.

The evolution of Sex-linked barring alleles in chickens involves both regulatory and coding changes in CDKN2A.

Sex-linked barring is a fascinating plumage pattern in chickens recently shown to be associated with two non-coding and two missense mutations affecting the ARF transcript at the CDKN2A tumor suppressor locus. It however remained a mystery whether all four mutations are indeed causative and how they contribute to the barring phenotype. Here, we show that Sex-linked barring is genetically heterogeneous, and that the mutations form three functionally different variant alleles. The B0 allele carries only the two non-coding changes and is associated with the most dilute barring pattern, whereas the B1 and B2 alleles carry both the two non-coding changes and one each of the two missense mutations causing the Sex-linked barring and Sex-linked dilution phenotypes, respectively. The data are consistent with evolution of alleles where the non-coding changes occurred first followed by the two missense mutations that resulted in a phenotype more appealing to humans. We show that one or both of the non-coding changes are cis-regulatory mutations causing a higher CDKN2A expression, whereas the missense mutations reduce the ability of ARF to interact with MDM2. Caspase assays for all genotypes revealed no apoptotic events and our results are consistent with a recent study indicating that the loss of melanocyte progenitors in Sex-linked barring in chicken is caused by premature differentiation and not apoptosis. Our results show that CDKN2A is a major locus driving the differentiation of avian melanocytes in a temporal and spatial manner.

Dominant Red Coat Color in Holstein Cattle Is Associated with a Missense Mutation in the Coatomer Protein Complex, Subunit Alpha (COPA) Gene.

Coat color in Holstein dairy cattle is primarily controlled by the melanocortin 1 receptor (MC1R) gene, a central determinant of black (eumelanin) vs. red/brown pheomelanin synthesis across animal species. The major MC1R alleles in Holsteins are Dominant Black (MC1RD) and Recessive Red (MC1Re). A novel form of dominant red coat color was first observed in an animal born in 1980. The mutation underlying this phenotype was named Dominant Red and is epistatic to the constitutively activated MC1RD. Here we show that a missense mutation in the coatomer protein complex, subunit alpha (COPA), a gene with previously no known role in pigmentation synthesis, is completely associated with Dominant Red in Holstein dairy cattle. The mutation results in an arginine to cysteine substitution at an amino acid residue completely conserved across eukaryotes. Despite this high level of conservation we show that both heterozygotes and homozygotes are healthy and viable. Analysis of hair pigment composition shows that the Dominant Red phenotype is similar to the MC1R Recessive Red phenotype, although less effective at reducing eumelanin synthesis. RNA-seq data similarly show that Dominant Red animals achieve predominantly pheomelanin synthesis by downregulating genes normally required for eumelanin synthesis. COPA is a component of the coat protein I seven subunit complex that is involved with retrograde and cis-Golgi intracellular coated vesicle transport of both protein and RNA cargo. This suggests that Dominant Red may be caused by aberrant MC1R protein or mRNA trafficking within the highly compartmentalized melanocyte, mimicking the effect of the Recessive Red loss of function MC1R allele.