Abstract
Structural variations (SVs) represent a large fraction of all genetic diversity, but how this genetic diversity is translated into phenotypic and organismal diversity is unclear. Explosive diversification of dog coat color and patterns after domestication can provide a unique opportunity to explore this question; however, the major obstacle is to efficiently collect a sufficient number of individuals with known phenotypes and genotypes of hundreds of thousands of markers. Using customer-provided information about coat color and patterns of dogs tested on a commercial canine genotyping platform, we identified a genomic region on chromosome 38 that is strongly associated with a mottled coat pattern (roaning) by genome-wide association study. We identified a putative causal variant in this region, an 11-kb tandem duplication (11,131,835-11,143,237) characterized by sequence read coverage and discordant reads of whole-genome sequence data, microarray probe intensity data, and a duplication-specific PCR assay. The tandem duplication is in an intronic region of usherin gene (USH2A), which was perfectly associated with roaning but absent in non-roaned dogs. We detected strong selection signals in this region characterized by reduced nucleotide diversity (π), increased runs of homozygosity, and extended haplotype homozygosity in Wirehaired Pointing Griffons and Australian Cattle Dogs (typically roaned breeds), as well as elevated genetic difference (FST) between Wirehaired Pointing Griffon (roaned) and Labrador Retriever (non-roaned). Surprisingly, all Dalmatians (N = 262) carried the duplication embedded in identical or similar haplotypes with roaned dogs, indicating this region as a shared target of selection during the breed's formation. We propose that the Dalmatian's unique spots were a derived coat pattern by establishing a novel epistatic interaction between roaning "R-locus" on chromosome 38 and an uncharacterized modifier locus. These results highlight the utility of consumer-oriented genotype and phenotype data in the discovery of genomic regions contributing to phenotypic diversity in dogs.
Highlights
Diverse coat colors and patterns observed in dogs and other domestic animals have long fascinated breeders
The most significant marker was at the Genetic basis of roaned coat in dogs position 11,085,443 on CFA38, an exonic region of usherin gene (USH2A) (P = 6.9 x 10−46)
The second most significant marker was on CFA13 at the position 8,625,896 that was in an intronic region of R-spondin 2 gene (RSPO2) (P = 1.1 x 10−29)
Summary
Diverse coat colors and patterns observed in dogs and other domestic animals have long fascinated breeders. Years of research on the genetics of coat color have led to the identification of a number of genes that have been repeatedly involved in the formation of diverse color morphs in both wild and domesticated animals [1]. One of the wellknown genes involved in the repeated evolution of light and dark color polymorphisms is the melanocortin-1 receptor (MC1R) that modulates the activity of the melanin synthesis pathways in the fur, plumage, scales and skin of mammals, birds, reptiles, amphibians, and fish [2]. Similar coloration has independently evolved in multiple lineages via mutations in different genes (e.g., LYST and AIM1 in polar bears and KIT and MATP in horses with white coats) [3,4,5]. High conservation of melanogenesis pathways across vertebrates warrants transformative research in human genomics research, such as the case of MC1R that is strongly associated with increased risk for melanoma [6,7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
