Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on horse chromosome 6

BackgroundEquine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. The disease is in agreement with a codominant mode of inheritance in our horse material. Animals presumed to be heterozygous for the mutant allele have cysts originating from the temporal ciliary body, peripheral retina and/or iris. In contrast, animals predicted to be homozygous for the disease-causing allele possess a wide range of multiple abnormalities, including iridociliary and/or peripheral retinal cysts, iridocorneal angle abnormalities, cornea globosa, iris hypoplasia and congenital cataracts. MCOA is most common in the Rocky Mountain horse breed where it occurs at a high frequency among Silver colored horses. The Silver coat color is associated with mutations inPMEL17that resides on ECA6q23. To map theMCOAlocus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for theMCOAlocus.ResultsWe performed linkage analysis within 17 paternal half-sib families of the Rocky Mountain horse breed. More than half of the 131 offspring had the Cyst phenotype and about one third had MCOA. Segregation data were obtained by genotyping 10 microsatellite markers most of which are positioned on ECA6q22-23, as well as the missense mutation for the Silver phenotype inPMEL17. Significant linkage was found between theMCOAlocus and eight of the genetic markers, where markerUPP5(Theta = 0, z = 12.3),PMEL17ex11(Theta = 0, z = 19.0) andUPP6(Theta = 0, z = 17.5) showed complete linkage with theMCOAlocus. DNA sequencing ofPMEL17in affected and healthy control individuals did not reveal any additional mutations than the two mutations associated with the Silver coat color.ConclusionTheMCOAlocus can with high confidence be positioned within a 4.9 megabase (Mb) interval on ECA6q. The genotype data onUPP5,PMEL17ex11andUPP6strongly support the hypothesis that horses with the Cyst phenotype are heterozygous for the mutant allele and that horses with the MCOA phenotype are homozygous for the mutant allele.