What is MCOA?

Multiple Congenital Ocular Anomalies (MCOA) and the Silver Gene

An overview of MCOA, its link with the silver coat colour gene, and why testing is important for owners, breeders, and clinicians.

A guide when considering breeding plans and horse management.

What is MCOA?

MCOA is an inherited eye condition linked to the silver dilution gene, PMEL17, which codes for pre-melanosomal protein 17, vital for melanosome function in melanocytes. This single genetic mutation causes both the distinctive silver coat colour and ocular abnormalities.

The Silver Gene (PMEL17)

• Location: chromosome 6 (ECA6q)
• Mutation: specific missense mutation in exon 11 of PMEL17
• Inheritance: incompletely dominant (severity depends on 1 vs 2 copies, i.e., heterozygous vs homozygous)

How Silver Affects Coat Colour

• Black base: dilutes to chocolate with flaxen/silver mane and tail, often with dapples.
• Bay base: dark points diluted, flaxen/silver mane and tail (red/bay silvers).
• Chestnut base: no visible change, but can still carry MCOA.

Inheritance and Genotypes

• N/N = normal: no silver, no MCOA risk.
• Z/N = heterozygous: silver dilute, mild MCOA (cysts).
• Z/Z = homozygous: silver dilute, severe MCOA (multiple eye defects).

Clinical Signs
• Z/N (heterozygous): mild ocular cysts, usually little impact on vision.
• Z/Z (homozygous): severe abnormalities including cysts, cataracts, glaucoma, enlarged cornea, abnormal iris/retina.

Testing for MCOA

Recommended testing involves BOTH genetic testing and ophthalmic exams:

1. Genetic Testing
2. Ophthalmic Examination

• Pull 20–40 mane/tail hairs with roots.
• Send to accredited labs
• Results show N/N, Z/N, or Z/Z genotype.
• Pupils dilated with 1% tropicamide.
• Exam with slit lamp, ophthalmoscope, tonometer.
• Detects cysts, iris/retina changes, and other abnormalities.

Breeds Affected

Silver dilution and MCOA occur not just in the Rocky Mountain Horse, but in the Kentucky Mountain Horse, Mountain Pleasure Horse, Icelandic Horse/Pony, Morgan, Miniature Horse, Missouri Foxtrotter, Gypsy Cob/Vanner, Appaloosa, Arabian, Shetland, Welsh Pony, Swedish Warmblood, and related breeds.

Key Points

• The silver gene affects both coat colour and eye health.
• Z/N horses: silver colour, mild MCOA effects.
• Z/Z horses: silver colour, severe MCOA effects.
• Chestnuts: no coat change, but can still carry and will exhibit MCOA.
• Always combine genetic and eye exams for responsible breeding.

ARTICLES ON GENETICS

Information is reproduced from the RMHA website with permission

A WORD OF CAUTION REGARDING THE INFORMATION PROVIDED HERE
Please be aware of the dates on the following articles. Some of the information in these articles may be of historical interest only. New or more up-to-date information may be available.

For a copy of, or to read the full report of the article below visit the RMHA website.

REPORT TO ROCKY MOUNTAIN HORSE ASSOCIATION
GENETIC SURVEY OF THE PMEL17/ SILVER MUTATION WHICH CAUSES MULTIPLE CONGENITAL OCULAR ANOMALIES (MCOA)

Final Draft accepted by RMHA Board: 3 October 2020

Prepared by Noah Anderson
Chair, Genetics Committee RMHA
Assistant Professor of Biology
Winona State University

Background

In a large study of 514 Rocky Mountain Horses, a group of congenital eye defects was first described in 1999 (Ramsey et al., 1999). Originally, these defects were lumped under the term Anterior Segment Dysgenesis (ASD). However, this syndrome of congenital defects has been re-termed Multiple Congenital Ocular Anomalies (hereafter referred to as MCOA) to more accurately represent the range of changes to the equine eye. It is beyond the scope of this report to summarize all of the eye defects present in MCOA, but rather, I give a brief overview (below).

Genetic testing has demonstrated that MCOA is caused by a mutation called PMEL17 located on the 6th chromosome of the horse genome (Andersson et al., 2013). It has also been demonstrated that PMEL17 is the mutation that causes the silver dapple/chocolate coloration found in horses. Since that original 1999 study, MCOA has been found in several more breeds (e.g., Kentucky mountain saddle horse, Mountain pleasure horse, Icelandic horse, Exmoor pony, Belgian draft horse, Shetland pony, American miniature horse, Comtois, Quarter horse, Morgan horse and any other breed that inherited PMEL17 mutation from its ancestors; Bellone, 2017) The widespread distribution of this gene in different breeds suggests that is has been present in the gene pool of horses since ancient times (Andersson et al., 2011).

The genetics of MCOA behaves in an incomplete dominant fashion—in other words, there is a gradual effect of the gene, depending on how many copies a horse possesses. Horses sort into three categories (affected, cysts only, normal). The letter Z is used as genetic shorthand for the presence of the PMEL17 mutation. The letter N is used for horses with a functional allele. That means that animals that are homozygous for the PMEL17/silver mutation (Z/Z) are affected with pronounced eye defects. Horses that are heterozygous for the silver mutation (Z/N) have only been found to have fluid filled cysts. Horses that lack PMEL17 (N/N) have normal eyes.

It is important to remember that while MCOA accounts for a range of eye defects, it is distinct from several other eye problems commonly found in horses. Common eye disorders that are NOT associated with MCOA include: primary glaucoma, equine recurrent uveitis, other forms of megaloglobus and acquired retinal detachment (among others; Premont and Knott 2020).

What do we know about MCOA?

1. It is caused by a gene called PMEL17, which also causes the silver (chocolate) coat coloration (Andersson et al., 2013).

2. The eye abnormalities seen in MCOA are more common and severe in homozygous silver (Z/Z) horses. These include but are not limited to: retinal detachment, retinal dysplasia, large, protrusive corneas (pop eyes), dysfunctional pupils that lack typical pupillary response, myopia (near-sightedness) and cataracts (Ramsey et al., 1999).

3. Horses that are heterozygous (Z/N) for silver typically have no major eye abnormalities, instead presenting with cysts within the eye. Studies have not been able to determine what effect, if any, cysts have on the eyesight of the horse.

4. To date, myopia (near-sightedness) has been shown to be the only progressive component of MCOA. This is true at least in heterozygous silver Icelandic horses older than 16 years (Johansson et al. 2017). Other defects have been found to be stable over the horse’s lifetime (Bellone, 2017).

5. Lastly, it is important to remember that not all eye problems are caused by MCOA. Horses, just like humans, can acquire or develop eye problems.

For a copy of, or to read the full report of the article below visit the RMHA website.

Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases

Lisa S. Andersson • Katarina Lyberg • Gus Cothran • David T. Ramsey • Rytis Juras • Sofia Mikko • Björn Ekesten • Susan Ewart • Gabriella Lindgren

Received: 29 November 2010 / Accepted: 8 March 2011 / Published online: 5 April 2011
©The Author(s) 2011. This article is published with open access at Springerlink.com

Abstract The syndrome Multiple Congenital Ocular Anomalies (MCOA) is the collective name ascribed to heritable congenital eye defects in horses. Individuals homozygous for the disease allele (MCOA phenotype) have a wide range of eye anomalies, while heterozygous horses (Cyst phenotype) predominantly have cysts that originate from the temporal ciliary body, iris, and/or peripheral retina. MCOA syndrome is highly prevalent in the Rocky Mountain Horse but the disease is not limited to this breed. Affected horses most often have a Silver coat color; however, a pleiotropic link between these phenotypes is yet to be proven. Locating and possibly isolating these traits would provide invaluable knowledge to scientists and breeders. This would favor maintenance of a desirable coat color while addressing the health concerns of the affected breeds, and would also provide insight into the genetic basis of the disease. Identical-by-descent mapping was used to narrow the previous 4.6-Mb region to a 264-kb interval for the MCOA locus. One haplotype common to four breeds showed complete association to the disease (Cyst phenotype, n = 246; MCOA phenotype, n = 83). Candidate genes from the interval, SMARCC2 and IKZF4, were screened for polymorphisms and genotyped, and segregation analysis allowed the MCOA syndrome region to be shortened to 208 kb. This interval also harbors PMEL17, the gene causative for Silver coat color. However, by shortening the MCOA locus by a factor of 20, 176 other genes have been unlinked from the disease and only 15 genes remain.

For a copy of, or to read the full report of the article below visit the RMHA website.

An Overview of Equine Multiple Congenital Ocular Anomalies (MCOA)

1 Susan Ewart, DVM, PhD, Dipl. ACVIM, and 2 David Ramsey, DVM, MS, Dipl. ACVO

1Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI

2Animal Ophthalmology Center, Williamston, MI

Introduction

Multiple Congenital Ocular Anomalies (MCOA, formerly called Anterior Segment Dysgenesis (ASD)) is an inherited eye disease of horses. The disease is congenital (present at birth) and generally does not progress in severity over the lifespan of an affected horse. Two types of ocular changes occur in association with the MCOA disease complex: 1) fluid-filled cysts that are present on the posterior iris, peripheral retina, or ciliary body, which is a structure within the eye that is located just behind the iris, and 2) cysts in combination with other ocular defects affecting the cornea, iris, lens, and/or retina (for details of the ocular defects, see Ramsey et al, 1999a). The two phenotypes are termed “cyst” and “MCOA,” respectively. Thorough ocular examination by a veterinary ophthalmologist or veterinarian familiar with clinical signs associated with this disease is required to diagnose cysts or MCOA. Cysts in particular can be very difficult to see and may require use of specialized equipment by a veterinary ophthalmologist to discern.