Mapping the locus for ocular melanosis in Cairn Terriers.

Objective: To map the disease locus for familial ocular melanosis (OM) in the Cairn Terrier.

Animals studied: Cairn Terriers with OM and normal control dogs.

Procedure: A genome-wide association study (GWAS) was performed using 63 OM-affected and 31 control Cairn Terriers, followed by haplotype analysis. A significantly associated single-nucleotide polymorphism was genotyped in a larger group of OM-affected and control Cairn Terriers. The coding and splice-site regions of genes mapping within the confidence interval were sequenced.

Results: A ~9.2 Mb region of chromosome 11 was significantly associated with OM. Haplotype analysis narrowed the region to 1.49 Mb. Genotyping of a SNP within the region showed 86% of OM-affected dogs were homozygous or heterozygous for the risk allele, whereas 78% of unaffected dogs were homozygous for the nonrisk allele. Sequencing of the coding regions and splice sites of four genes (c9orf72, IFNK, the 5' end of MOB3B, and the 3' end of LINGO2) and of a microRNA (MIR876) did not detect any genetic variants unique to OM-affected dogs.

Conclusion: OM in Cairn Terriers maps to a 1.49 Mb region of chromosome 11. This accounts for 86% of OM cases in our DNA bank. A second locus may account for the OM phenotype in the remaining 14% of cases. Sequencing of coding regions and splice sites of positional candidate genes and a microRNA did not reveal any genetic variants unique to affected dogs. Further studies are required to elucidate the DNA variant causal for OM in Cairn Terriers and to understand the disease mechanism.