Equine multiple congenital ocular anomalies and silver coat colour result from the pleiotropic effects of mutant PMEL

PLoS One. 2013 Sep 23;8(9):e75639. doi: 10.1371/journal.pone.0075639. eCollection 2013.


Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome is a heritable eye disorder mainly affecting silver colored horses. Clinically, the disease manifests in two distinct classes depending on the horse genotype. Horses homozygous for the mutant allele present with a wide range of ocular defects, such as iris stromal hypoplasia, abnormal pectinate ligaments, megaloglobus, iridociliary cysts and cataracts. The phenotype of heterozygous horses is less severe and predominantly includes iridociliary cysts, which occasionally extend into the temporal retina. In order to determine the genetic cause of MCOA syndrome we sequenced the entire previously characterized 208 kilobase region on chromosome 6 in ten individuals; five MCOA affected horses from three different breeds, one horse with the intermediate Cyst phenotype and four unaffected controls from two different breeds. This was performed using Illumina TruSeq technology with paired-end reads. Through the systematic exclusion of all polymorphisms barring two SNPs in PMEL, a missense mutation previously reported to be associated with the silver coat colour and a non-conserved intronic SNP, we establish that this gene is responsible for MCOA syndrome. Our finding, together with recent advances that show aberrant protein function due to the coding mutation, suggests that the missense mutation is causative and has pleiotrophic effect, causing both the horse silver coat color and MCOA syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Chromosomes / genetics
  • Eye Abnormalities / genetics*
  • Eye Abnormalities / metabolism
  • Genetic Association Studies / methods
  • Genotype
  • Heterozygote
  • Homozygote
  • Horse Diseases / genetics*
  • Horse Diseases / metabolism
  • Horses / genetics*
  • Horses / metabolism
  • Mutation, Missense / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Sequence Analysis, DNA
  • Silver / metabolism*


  • Silver

Grants and funding

Financial support was obtained from The Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (221-2009-1631), Swedish-Norwegian Foundation for Equine Research (H0947256 and H0847211) and Carl Trygger Foundation (CTS 08:29). Sequencing was performed by the SNP&SEQ Technology Platform in Uppsala. The platform is part of Science for Life Laboratory at Uppsala University and supported as a national infrastructure by the Swedish Research Council. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.