Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases

The syndrome Multiple Congenital Ocular Anomalies (MCOA) is the collective name ascribed to heritable congenital eye defects in horses. Individuals homozygous for the disease allele (MCOA phenotype) have a wide range of eye anomalies, while heterozygous horses (Cyst phenotype) predominantly have cysts that originate from the temporal ciliary body, iris, and/or peripheral retina. MCOA syndrome is highly prevalent in the Rocky Mountain Horse but the disease is not limited to this breed. Affected horses most often have a Silver coat color; however, a pleiotropic link between these phenotypes is yet to be proven. Locating and possibly isolating these traits would provide invaluable knowledge to scientists and breeders. This would favor maintenance of a desirable coat color while addressing the health concerns of the affected breeds, and would also provide insight into the genetic basis of the disease. Identical-by-descent mapping was used to narrow the previous 4.6-Mb region to a 264-kb interval for the MCOA locus. One haplotype common to four breeds showed complete association to the disease (Cyst phenotype, n = 246; MCOA phenotype, n = 83). Candidate genes from the interval, SMARCC2 and IKZF4, were screened for polymorphisms and genotyped, and segregation analysis allowed the MCOA syndrome region to be shortened to 208 kb. This interval also harbors PMEL17, the gene causative for Silver coat color. However, by shortening the MCOA locus by a factor of 20, 176 other genes have been unlinked from the disease and only 15 genes remain. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00335-011-9325-7) contains supplementary material, which is available to authorized users.