Dataset Information

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

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.

SUBMITTER: Andersson LS

PROVIDER: S-EPMC3781063 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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

Andersson Lisa S LS Wilbe Maria M Viluma Agnese A Cothran Gus G Ekesten Björn B Ewart Susan S Lindgren Gabriella G

PloS one 20130923 9

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 iridoc ...[more]

PMID: 24086599

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Project description:BACKGROUND: Equine 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. RESULTS: We 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. CONCLUSION: The 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.

Project description:BACKGROUND:The increasing popularity of alpacas and llamas outside of South America is undeniable. The associated limited genetic diversity raises questions about health and other genetically determined traits like coat colour. Therefore, a survey studying the prevalence of congenital disorders and coat colours and patterns in South American camelids was performed in Austria, Germany and Switzerland. Moreover, the motivation for keeping these animals, the herd size and breeds was assessed. RESULTS:A total of 146 questionnaires were returned corresponding to 16 farms from Austria, 69 farms from Germany, and 61 farms from Switzerland. In total, the returned surveys reported data on 2770 animals including?~?85% alpacas and?~?15% llamas. The most common alpaca breed was Huacaya (87.7%), the most common llama breed was Wooly (15.6%). Breeding (69.4%), wool production (63.3%) and keeping them as pets (53.7%) were the most common motivations to keep these animals, although this varied among countries. The three coat colour groups, solid white (24.8%), brown and black (64.8%) and grey (10.4%), occurred at different frequencies. About 7% of the South American camelids with solid white coat showed blue-pigmented eyes, corresponding to the known blue-eyed white phenotype, of which more than every second animal was apparently deaf. Uniform solid coloured animals occurred predominantly (81.4%), whereas pinto (8.8%), speckled (6.4%) and spotted (3.4%), also known as appaloosa, were comparably less prevalent. In total 161 observations of congenital disorders occurring during a 5-year-period were reported. The most prevalent disorders were in the group of musculoskeletal disorders such as spiral toe growth (16.4%), hyperextension of the fetlock joint (12.3%), angular limb deformities (11.0%) and axial rotation of the limbs (8.2%). CONCLUSIONS:This survey revealed first insights into the occurrence of different traits and disorders in the current South American camelid population of Austria, Germany, and Switzerland. The identification of the most common musculoskeletal disorders might encourage the breeders to eliminate affected animals from their breeding program to decrease the incidence although traits such as spiral toe growth might also represent phenocopies.

Dataset Information

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

Publications

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

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