Equine Multiple Congenital Ocular Anomalies and Silver Coat Colour Result from the Pleiotropic Effects of Mutant PMEL

Lisa S Andersson,Susan Ewart,Maria Wilbe,Gabriella Lindgren,Gus Cothran,Agnese Viluma,Björn Ekesten,Claire Wade

doi:10.1371/journal.pone.0075639

Abstract

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.

Highlights

Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of different combinations of clinical symptoms that affect the anterior and posterior segment of the eye
Additional horse breeds that have been diagnosed with MCOA syndrome include the Icelandic Horse, Shetland Pony, Exmoor Pony, American Miniature Horse, Belgian Draft and Morgan Horse, as well as the Kentucky Mountain Saddle Horse and Mountain Pleasure Horse, both of which are closely related to the Rocky Mountain Horse [1,2,3,4,5,6,7]
This study aimed at identifying the causative mutation of MCOA syndrome and in doing so, evaluate if PMEL is involved in this eye disease

Summary

Introduction

Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome consists of different combinations of clinical symptoms that affect the anterior and posterior segment of the eye. Horses with the MCOA phenotype are homozygous for the disease allele and have a wide range of eye anomalies (Figure 1a and b). These include, but are not restricted to, uveal cysts, cornea globosa, iris stromal hypoplasia, abnormal pectinate ligaments, cataracts and iris hypoplasia [1,8,9]. The majority of MCOA syndrome horses have the valued Silver coat color (Figure 1c).

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Conclusion