Equine multiple congenital ocular anomalies and silver coat colour result from the pleiotropic effects of mutant PMEL.
Authors: Andersson Lisa S, Wilbe Maria, Viluma Agnese, Cothran Gus, Ekesten Björn, Ewart Susan, Lindgren Gabriella
Journal: PloS one
Summary
Multiple congenital ocular anomalies (MCOA) syndrome represents a significant heritable condition in horses, particularly those with silver coat colouration, manifesting as a spectrum of defects including iris stromal hypoplasia, pectinate ligament abnormalities, megaloglobus, iridociliary cysts and cataracts in homozygous carriers, whilst heterozygotes typically present with the milder iridociliary cyst phenotype. Andersson and colleagues sequenced a 208 kilobase region on equine chromosome 6 in ten horses (five MCOA-affected individuals, one with intermediate cyst phenotype, and four unaffected controls) using Illumina TruSeq technology, systematically excluding polymorphisms until two SNPs in the PMEL gene remained as candidates. The researchers identified a missense mutation in PMEL—previously associated with silver coat colour—as the causative variant, demonstrating pleiotrophic effects whereby a single genetic mutation produces both the distinctive silver phenotype and ocular disease. This discovery has direct implications for breeding programmes, particularly in breeds carrying the silver allele, as genetic testing can now identify carriers and affected individuals to minimise disease prevalence; furthermore, the shared molecular pathway between coat colour and ocular pathology suggests that future therapeutic approaches targeting aberrant PMEL protein function could potentially address both manifestations of this condition.
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Practical Takeaways
- •Silver coat colour in horses is genetically linked to MCOA syndrome; breeders should screen breeding animals for this heritable condition regardless of coat colour phenotype
- •Clinical presentation varies by genotype—homozygous affected horses have severe multiple ocular defects while heterozygotes primarily develop iridociliary cysts, useful for diagnosis and prognostication
- •Genetic testing for the PMEL mutation can identify affected and carrier animals, enabling informed breeding decisions to reduce disease incidence in affected breed populations
Key Findings
- •A missense mutation in the PMEL gene on equine chromosome 6 is responsible for MCOA syndrome and silver coat colour
- •Homozygous horses for the mutant allele present severe ocular defects including iris hypoplasia, abnormal pectinate ligaments, megaloglobus, iridociliary cysts and cataracts
- •Heterozygous horses show a milder phenotype predominantly featuring iridociliary cysts that may extend into the temporal retina
- •The PMEL mutation exhibits pleiotropic effects, causing both silver coat colour and ocular anomalies through aberrant protein function