Abstract
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 in PMEL17 that resides on ECA6q23. To map the MCOA locus we analyzed 11 genetic markers on ECA6q and herein describe a chromosome interval for the MCOA locus.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 in PMEL17. Significant linkage was found between the MCOA locus and eight of the genetic markers, where marker UPP5 (Theta = 0, z = 12.3), PMEL17ex11 (Theta = 0, z = 19.0) and UPP6 (Theta = 0, z = 17.5) showed complete linkage with the MCOA locus. DNA sequencing of PMEL17 in affected and healthy control individuals did not reveal any additional mutations than the two mutations associated with the Silver coat color.ConclusionThe MCOA locus can with high confidence be positioned within a 4.9 megabase (Mb) interval on ECA6q. The genotype data on UPP5, PMEL17ex11 and UPP6 strongly 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.
Highlights
Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye
Genotyping and Linkage analysis We performed linkage analysis by genotyping 17 paternal half-sib Rocky Mountain horse families segregating for the MCOA locus
Four families were used for identification of an initial and broader interval for the MCOA locus (Figure 3)
Summary
Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of a diverse set of abnormalities predominantly localized to the frontal part of the eye. MCOA is most common in the Rocky Mountain horse breed where it occurs at a high frequency among Silver colored horses. The fact that five out of seven of the ancestral stallion's first-generation offspring had ocular abnormalities suggests that this individual did carry the mutant allele Extensive breeding from this foundation sire's offspring has propagated the causative mutation(s), leading to a high frequency of MCOA syndrome in the Rocky Mountain horse population. There are numerous examples where intense and selective breeding of a few lineages has led to a high occurrence of undesired traits in domesticated animals Examples of such are hyperkalaemic periodic paralysis (HYPP) among Quarter Horses [5] and severe combined immunodeficiency disease (SCID) in Arabian horses [6,7]. The negative effects of breed development from a limited number of individuals and/or inbreeding is evident in dogs, with several cases of high incidence of inherited diseases within modern purebreds [8]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call