Atypical Genotypes for Canine Agouti Signaling Protein Suggest Novel Chromosomal Rearrangement

Abstract

<jats:p>Canine coat color is a readily observed phenotype of great interest to dog enthusiasts; it is also an excellent avenue to explore the mechanisms of genetics and inheritance. As such, multiple commercial testing laboratories include basic color alleles in their popular screening panels, allowing for the creation of genotyped datasets at a scale not before appreciated in canine genetic research. These vast datasets have revealed rare genotype anomalies that encourage further exploration of color and pattern inheritance. We previously reported the simultaneous presence of greater than two allele variants at the Agouti Signaling Protein (ASIP) locus in a commercial genotype cohort of 11,790 canids. Here we present additional data to characterize the occurrence of anomalous ASIP genotypes. We document the detection of combinations of three or four ASIP allele variants in 17 dog breeds and Dingoes, at within-breed frequencies of 1.32–63.34%. We analyze the potential impact on phenotype that these allele combinations present, and propose mechanisms that could account for the findings, including: gene recombination, duplication, and incorrect causal variant identification. These findings speak to the accuracy of industry-wide protocols for commercial ASIP genotyping and imply that ASIP should be analyzed via haplotype, rather than using only the existing allele hierarchy, in the future.</jats:p>

Genome scans of dog behavior implicate a gene network underlying psychopathology in mammals, including humans

“…Text). Both loci are under strong evolutionary selection, but the coat-pattern alleles presumed to be under selection cannot be discerned from the present SNP genotype data 20 . Two cohorts had chr20 associations with escaping and owner-directed aggression; and single cohorts had associations with chasing, separation anxiety and separation-related urination.…”

Comprehensive genetic testing combined with citizen science reveals a recently characterized ancient MC1R mutation associated with partial recessive red phenotypes in dog

“…The expected coat colors for these dogs were a w wolf sable, a t tan point or a recessive black determined by their A locus (due to only wild type variant k y being present on the K locus of these dogs). A maximum copy number of two allelic variants at the A locus was found in any of the Tamaskan Dogs and no a y variant, indicating that no A locus anomalies were present as recently observed in a small number of other dog breeds [ 12 ]. The observed coat color phenotypes were in concordance with expected phenotypes for 26 of the Tamaskan Dogs, while 17 of the Tamaskan Dogs manifested more abundantly pheomelanic hairs in areas of head, legs and body on which the coat color pattern known as “domino” or “grizzle” is formed.…”

“…Such variable expression of ASIP expression and phenotype could be due to epigenetic mechanisms as shown in mice [ 10 , 11 ]. In addition, combinations of more than two allelic variants at the A locus were identified, with variable phenotypic manifestation, in a small number of dog breeds [ 12 ]. The canine beta-Defensin 103 ( CBD103 ) gene, known as the K locus, is a neutral antagonist of MC1R .…”

Comprehensive genetic testing combined with citizen science reveals a recently characterized ancient MC1R mutation associated with partial recessive red phenotypes in dog&nbsp;

“…Genotyping. Genotyping of coat color gene variants of MC1R (2-5), CBD103 (12,13) and ASIP (7-9) loci, and the R301C variant of the MC1R gene was carried out according to manufacturer-recommended standard protocols on a custom-designed Illumina In nium technology bead chip ( (41,42), Illumina, San Diego, Ca, USA). The genotyping quality control measures for this platform were previously described in (41,42).…”

“…Such variable expression of ASIP expression and phenotype could be due to epigenetic mechanisms as shown in mice (10,11). In addition, combinations of more than two allelic variants at the A locus were identi ed, with variable phenotypic manifestation, in a small number of dog breeds (12). The canine beta-Defensin 103 (CBD103) gene, known as the K locus, is a neutral antagonist of MC1R.…”