Association Study of Candidate Genes for Primary Cataracts and Fine-mapping of a Candidate Region on Dog Chromosome 1 in Entlebucher Mountain Dogs

Purpose: The Entlebucher mountain dog (EMD) shows a high incidence of primary non-congenital cataracts (CAT). Because of the late-onset of CAT, it is difficult to exclude affected animals from breeding. A screen of candidate genes should help to identify the genes associated with CAT in EMD.

Methods: We genotyped 39 flanking microsatellite markers for 31 cataract candidate genes in 10 EMD families and tested them for linkage and association. For delimitation of a linked chromosome region on canine chromosome 1 (CFA1), we interrogated CFA1 by genotyping 30 additional microsatellites. We also sequenced the whole coding sequence with flanking intronic and untranslated regions of two candidate genes on CFA1.

Results: We found a genome-wide significant genomic region on CFA1, which showed a significantly associated haplotype with the CAT phenotype in the EMDs. Sequencing two candidate genes located on CFA1 revealed three single nucleotide polymorphisms (SNPs), which were not associated with CAT.

Conclusions: We identified a putative CAT region that peaked at 96.07 Mb with genome-wide significant test statistics and extended over 1.3 Mb on CFA1 in the EMD. A significant marker-trait association based on haplotypes corroborated this CAT region. Further research is necessary to determine the gene responsible for CAT that is harbored by this linked and associated genomic region.