Comparative FISH-Mapping of MC1R, ASIP, and TYRP1 in New and Old World Camelids and Association Analysis With Coat Color Phenotypes in the Dromedary (Camelus dromedarius)

Abstract

Melanocortin 1 receptor ( MC1R ), the agouti signaling protein ( ASIP ), and tyrosinase related protein 1 ( TYRP1 ) are among the major regulators of pigmentation in mammals. Recently, MC1R and ASIP sequence variants were associated with white and black/dark brown coat colors, respectively, in the dromedary. Here we confirmed this association by independent sequencing and mutation discovery of MC1R and ASIP coding regions and by TaqMan genotyping in 188 dromedaries from Saudi Arabia and United States, including 38 black, 53 white, and 97 beige/brown/red animals. We showed that heterozygosity for a missense mutation c.901C > T in MC1R is sufficient for the white coat color suggesting a possible dominant negative effect. Likewise, we confirmed that the majority of black dromedaries were homozygous for a frameshift mutation in ASIP exon 2, except for 4 animals, which were heterozygous. In search for additional mutations underlying the black color, we identified another frameshift mutation in ASIP exon 4 and 6 new variants in MC1R including a significantly associated SNP in 3′UTR. In pursuit of sequence variants that may modify dromedary wild-type color from dark-reddish brown to light beige, we identified 4 SNPs and one insertion in TYRP1 non-coding regions. However, none of these were associated with variations in wild-type colors. Finally, the three genes were cytogenetically mapped in New World (alpaca) and Old World (dromedary and Bactrian camel) camelids. The MC1R was assigned to chr21, ASIP to chr19 and TYRP1 to chr4 in all 3 species confirming extensive conservation of camelid karyotypes. Notably, while the locations of ASIP and TYRP1 were in agreement with human-camelid comparative map, mapping MC1R identified a new evolutionary conserved synteny segment between camelid chromosome 21 and HSA16. The findings contribute to coat color genomics and the development of molecular tests in camelids and toward the chromosome level reference assemblies of camelid genomes.

Genome-wide genetic structure and selection signatures for color in 10 traditional Chinese yellow-feathered chicken breeds

“…The 10 YFC populations divide into northern, central and southern clusters, agreeing with the trends earlier proposed by microsatellite-based studies of chickens from these regions of China [1,11,12]. This sub-structuring may be reflective of some extent of differential exchange of genetic materials in neighboring locations, breeding histories, or natural and artificial selection drivers as described in several chicken populations [16,34]. This explains the existence of genomic grouping among populations with close phenotypic appearances such as the YFCs.…”

“…ASIP gene codes for agoutisignaling protein, which antagonizes the α-MSH hormone (melanocyte stimulating hormone) for the melanocyte-1 receptor (MC1R) counteracting the production of eumelanin (black/brown melanin) and favoring the synthesis of pheomelanin (yellow/red melanin) [33]. Both ASIP and MC1R are genes which continue to be synonymous with nearly all studies on pigmentation in mammalian and avian species [34][35][36][37][38]. Interestingly, it has been demonstrated that a >90kb deletion upstream of avian ASIP, encompassing portions of the RALY locus, places ASIP under the regulatory control of RALY promoter [39].…”

Genome-wide genetic structure and selection signatures for color in 10 traditional Chinese yellow-feathered chicken breeds

“…The 10 YFC populations divide into northern, central and southern clusters, agreeing with the trends earlier proposed by microsatellite-based studies of chickens from these regions of China [1,11,12]. This sub-structuring may be reflective of some extent of differential exchange of genetic materials in neighboring locations, breeding histories, or natural and artificial selection drivers as described in several chicken populations [16,34]. This explains the existence of genomic grouping among populations with close phenotypic appearances such as the YFCs.…”

“…ASIP gene codes for agoutisignaling protein, which antagonizes the α-MSH hormone (melanocyte stimulating hormone) for the melanocyte-1 receptor (MC1R) counteracting the production of eumelanin (black/brown melanin) and favoring the synthesis of pheomelanin (yellow/red melanin) [33]. Both ASIP and MC1R are genes which continue to be synonymous with nearly all studies on pigmentation in mammalian and avian species [34][35][36][37][38]. Interestingly, it has been demonstrated that a >90kb deletion upstream of avian ASIP, encompassing portions of the RALY locus, places ASIP under the regulatory control of RALY promoter [39].…”

Chromosomal Localization of Candidate Genes for Fiber Growth and Color in Alpaca (Vicugna pacos)

“…Mutations in this gene have shown to cause the black coat color phenotype in different species, such as guinea pigs (Lai et al, 2019), black-bone chicken (Yu et al, 2019), sheep (Norris and Whan, 2008; Royo et al, 2008), Iranian Markhoz goats (Nazari-Ghadikolaei et al, 2018), donkeys (Abitbol et al, 2015), horses (Rieder et al, 2001), dogs (Kerns et al, 2004), cats (Eizirik et al, 2003), and impala antelope (Miller et al, 2016). In camelids the agouti signaling protein gene ( ASIP ) is involved in fiber color development in alpacas (Bathrachalam et al, 2011; Chandramohan et al, 2013), llamas (Daverio et al, 2016) and dromedaries (Almathen et al, 2018; Alshanbari et al, 2019). Sequence variants (SNPs) in other genes from this linkage group have been associated with color phenotypes in several mammalian species.…”