Association study of candidate genes for primary cataracts and fine-mapping of a candidate region on dog chromosome 1 in Entlebucher mountain dogs.
OBJECTIVE
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.
Müller
Christina
C
Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Distl
Ottmar
O
D000818:Animals; D002386:Cataract / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000235:genetics*; D004252:DNA Mutational Analysis; D004285:Dogs / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics; D005293:Ferritins / Q000235:genetics; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D018895:Microsatellite Repeats / Q000235:genetics; D020161:Physical Chromosome Mapping
D005136:Eye Proteins; D005293:Ferritins