FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
BMC genetics2008; 9; 88; doi: 10.1186/1471-2156-9-88

Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on horse chromosome 6.

Abstract: 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. Conclusions: 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.
Get Full Text
Publication Date: 2008-12-19 PubMed ID: 19099555PubMed Central: PMC2653074DOI: 10.1186/1471-2156-9-88Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the genetic origins of Equine Multiple Congenital Ocular Anomalies (MCOA) in horses, locating the responsible gene within a 4.9 megabase interval on horse chromosome 6.

Background on MCOA

  • MCOA is a syndrome manifested through a range of eye abnormalities, particularly located in the frontal part of the horse’s eye.
  • This genetic disorder is primarily observed in the Rocky Mountain horse breed, especially in those with Silver coat color.
  • The different repercussions of the disorder depend on whether the horse is heterozygous or homozygous for the genetic mutation causing the syndrome.
  • Heterozygous animals typically have cysts originating from several parts of the eye whereas homozygous animals may experience more severe abnormalities such as cornea globosa, iris hypoplasia, and congenital cataracts.

Investigation of Genetic Markers

  • The study analyzed 11 genetic markers on ECA6q, the horse chromosome region where PMEL17, the gene associated with the Silver coat color, resides.
  • A total of 17 paternal half-sib families of the Rocky Mountain horse breed were subjected to a linkage analysis.
  • Of the 131 offspring horses, over half showed the cyst phenotype associated with the mutant allele, while about one third were diagnosed with MCOA.
  • The diagnosis was confirmed by genotyping 10 microsatellite markers positioned mainly on ECA6q22-23, as well as the missense mutation responsible for the Silver phenotype in PMEL17.

Linkage Analysis and Conclusions

  • The MCOA locus showed significant linkage with eight of the genetic markers, but complete linkage was found with three specific markers: UPP5, PMEL17ex11, and UPP6.
  • No other mutations were detected in PMEL17, apart from the two already associated with the Silver coat color.
  • Based on these results, researchers concluded that the MCOA locus is very likely located within a 4.9 megabase (Mb) interval on ECA6q.
  • This data provides strong evidence that horses with the Cyst phenotype are heterozygous for the mutant allele and horses diagnosed with MCOA are homozygous for the mutant allele.

Cite This Article

APA
Andersson LS, Juras R, Ramsey DT, Eason-Butler J, Ewart S, Cothran G, Lindgren G. (2008). Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on horse chromosome 6. BMC Genet, 9, 88. https://doi.org/10.1186/1471-2156-9-88

Publication

BMC genetics
ISSN: 1471-2156
NlmUniqueID: 100966978
Country: England
Language: English
Volume: 9
Pages: 88

Researcher Affiliations

Andersson, Lisa S
  • Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden. Lisa.Andersson@hgen.slu.se
Juras, Rytis
    Ramsey, David T
      Eason-Butler, Jessica
        Ewart, Susan
          Cothran, Gus
            Lindgren, Gabriella

              MeSH Terms

              • Alleles
              • Animals
              • Chromosome Mapping
              • Chromosomes, Mammalian / genetics
              • Eye Abnormalities / genetics
              • Eye Abnormalities / veterinary
              • Genetic Markers
              • Genotype
              • Horses / genetics
              • Microsatellite Repeats
              • Pedigree
              • Phenotype
              • Sequence Analysis, DNA

              References

              This article includes 28 references
              1. Ramsey DT, Ewart SL, Render JA, Cook CS, Latimer CA. Congenital ocular abnormalities of Rocky Mountain Horses.. Vet Ophthalmol 1999;2:47–59.
                doi: 10.1046/j.1463-5224.1999.00050.xpubmed: 11397242google scholar: lookup
              2. Grahn BH, Pinard C, Archer S, Bellone R, Forsyth G, Sandmeyer LS. Congenital ocular anomalies in purebred and crossbred Rocky and Kentucky Mountain horses in Canada.. Can Vet J 2008;49:675–681.
                pmc: PMC2430397pubmed: 18827844
              3. Roberts SM. Congenital ocular anomalies.. Vet Clin North Am Equine Pract 1992;8:459–478.
                pubmed: 1458324
              4. Crowe MW, Swerczek TW. Equine congenital defects.. Am J Vet Res 1985;46:353–358.
                pubmed: 3994101
              5. Rudolph JA, Spier SJ, Byrns G, Hoffman EP. Linkage of hyperkalaemic periodic paralysis in quarter horses to the horse adult skeletal muscle sodium channel gene.. Anim Genet 1992;23:241–250.
                pubmed: 1323940
              6. Wiler R, Leber R, Moore BB, VanDyk LF, Perryman LE, Meek K. Equine severe combined immunodeficiency: a defect in V(D)J recombination and DNA-dependent protein kinase activity.. Proc Natl Acad Sci USA 1995;92:11485–11489.
                doi: 10.1073/pnas.92.25.11485pmc: PMC40426pubmed: 8524788google scholar: lookup
              7. Shin EK, Perryman LE, Meek K. A kinase-negative mutation of DNA-PK(CS) in equine SCID results in defective coding and signal joint formation.. J Immunol 1997;158:3565–3569.
                pubmed: 9103416
              8. Ostrander EA, Wayne RK. The canine genome.. Genome Res 2005;15:1706–1716.
                doi: 10.1101/gr.3736605pubmed: 16339369google scholar: lookup
              9. Ewart SL, Ramsey DT, Xu J, Meyers D. The horse homolog of congenital aniridia conforms to codominant inheritance.. J Hered 2000;91:93–98.
                doi: 10.1093/jhered/91.2.93pubmed: 10768120google scholar: lookup
              10. Ramsey DT, Hauptman JG, Petersen-Jones SM. Corneal thickness, intraocular pressure, and optical corneal diameter in Rocky Mountain Horses with cornea globosa or clinically normal corneas.. Am J Vet Res 1999;60:1317–1321.
                pubmed: 10791948
              11. Brunberg E, Andersson L, Cothran G, Sandberg K, Mikko S, Lindgren G. A missense mutation in PMEL17 is associated with the Silver coat color in the horse.. BMC Genet 2006;7:46.
                doi: 10.1186/1471-2156-7-46pmc: PMC1617113pubmed: 17029645google scholar: lookup
              12. Kerje S, Sharma P, Gunnarsson U, Kim H, Bagchi S, Fredriksson R, Schutz K, Jensen P, von Heijne G, Okimoto R. The Dominant white, Dun and Smoky color variants in chicken are associated with insertion/deletion polymorphisms in the PMEL17 gene.. Genetics 2004;168:1507–1518.
                doi: 10.1534/genetics.104.027995pmc: PMC1448810pubmed: 15579702google scholar: lookup
              13. Schonthaler HB, Lampert JM, von Lintig J, Schwarz H, Geisler R, Neuhauss SC. A mutation in the silver gene leads to defects in melanosome biogenesis and alterations in the visual system in the zebrafish mutant fading vision.. Dev Biol 2005;284:421–436.
                doi: 10.1016/j.ydbio.2005.06.001pubmed: 16024012google scholar: lookup
              14. Dausch D, Wegner W, Michaelis W, Reetz I. [Eye changes in the merle syndrome in the dog (author's transl)]. Albrecht Von Graefes Arch Klin Exp Ophthalmol 1978;206:135–150.
                doi: 10.1007/BF00414621pubmed: 418699google scholar: lookup
              15. Gelatt KN, Powell NG, Huston K. Inheritance of microphthalmia with coloboma in the Australian shepherd dog.. Am J Vet Res 1981;42:1686–1690.
                pubmed: 7325429
              16. Clark LA, Wahl JM, Rees CA, Murphy KE. Retrotransposon insertion in SILV is responsible for merle patterning of the domestic dog.. Proc Natl Acad Sci USA 2006;103:1376–1381.
                doi: 10.1073/pnas.0506940103pmc: PMC1360527pubmed: 16407134google scholar: lookup
              17. Green P, Falls KA, Crooks S. Documentation for CRI-MAP, version 2.4.. Washington Univ, School Med St Louis, MO 1990.
              18. Ensembl
              19. Wade CM, Gnerre S, Garber M, Broad Institute Genome Sequencing and Analysis Team, Lander E, Lindblad-Toh K, Community twtEGS. Preliminary analysis of the equine genome sequence.. Plant & Animal Genomes XVI Conference 2008;W141:34.
              20. Schedl A, Ross A, Lee M, Engelkamp D, Rashbass P, van Heyningen V, Hastie ND. Influence of PAX6 gene dosage on development: overexpression causes severe eye abnormalities.. Cell 1996;86:71–82.
                doi: 10.1016/S0092-8674(00)80078-1pubmed: 8689689google scholar: lookup
              21. Sowden JC. Molecular and developmental mechanisms of anterior segment dysgenesis.. Eye 2007;21:1310–1318.
                doi: 10.1038/sj.eye.6702852pubmed: 17914434google scholar: lookup
              22. Pal B, Mohamed MD, Keen TJ, Williams GA, Bradbury JA, Sheridan E, Inglehearn CF. A new phenotype of recessively inherited foveal hypoplasia and anterior segment dysgenesis maps to a locus on chromosome 16q23.2-24.2.. J Med Genet 2004;41:772–777.
                doi: 10.1136/jmg.2004.020040pmc: PMC1735603pubmed: 15466012google scholar: lookup
              23. UCSC Genome Browser
              24. Benson G. Tandem repeats finder: a program to analyze DNA sequences.. Nucleic Acids Res 1999;27:573–580.
                doi: 10.1093/nar/27.2.573pmc: PMC148217pubmed: 9862982google scholar: lookup
              25. Rozen S, Skaletsky H. Primer3 on the WWW for general users and for biologist programmers.. Methods Mol Biol 2000;132:365–386.
                pubmed: 10547847
              26. Pielberg G, Olsson C, Syvanen AC, Andersson L. Unexpectedly high allelic diversity at the KIT locus causing dominant white color in the domestic pig.. Genetics 2002;160:305–311.
                pmc: PMC1461930pubmed: 11805065
              27. Chowdhary BP, Raudsepp T, Kata SR, Goh G, Millon LV, Allan V, Piumi F, Guerin G, Swinburne J, Binns M. The first-generation whole-genome radiation hybrid map in the horse identifies conserved segments in human and mouse genomes.. Genome Res 2003;13:742–751.
                doi: 10.1101/gr.917503pmc: PMC430160pubmed: 12671008google scholar: lookup
              28. Tozaki T, Penedo MC, Oliveira RP, Katz JP, Millon LV, Ward T, Pettigrew DC, Brault LS, Tomita M, Kurosawa M. Isolation, characterization and chromosome assignment of 341 newly isolated equine TKY microsatellite markers.. Anim Genet 2004;35:487–496.
                doi: 10.1111/j.1365-2052.2004.01208.xpubmed: 15566484google scholar: lookup

              Citations

              This article has been cited 13 times.
              1. Reddy RM, Lakra MS, Meshram RJ, Taksande A, Wanjari MB. A Rare Variant and Unusual Presentation of Holt Oram Syndrome in a Child. Cureus 2022 Nov;14(11):e31076.
                doi: 10.7759/cureus.31076pubmed: 36475197google scholar: lookup
              2. Ishishita S, Takahashi M, Yamaguchi K, Kinoshita K, Nakano M, Nunome M, Kitahara S, Tatsumoto S, Go Y, Shigenobu S, Matsuda Y. Nonsense mutation in PMEL is associated with yellowish plumage colour phenotype in Japanese quail. Sci Rep 2018 Nov 13;8(1):16732.
                doi: 10.1038/s41598-018-34827-4pubmed: 30425278google scholar: lookup
              3. Johansson MK, Jäderkvist Fegraeus K, Lindgren G, Ekesten B. The refractive state of the eye in Icelandic horses with the Silver mutation. BMC Vet Res 2017 Jun 2;13(1):153.
                doi: 10.1186/s12917-017-1059-7pubmed: 28577553google scholar: lookup
              4. Reissmann M, Musa L, Zakizadeh S, Ludwig A. Distribution of coat-color-associated alleles in the domestic horse population and Przewalski's horse. J Appl Genet 2016 Nov;57(4):519-525.
                doi: 10.1007/s13353-016-0352-7pubmed: 27194311google scholar: lookup
              5. Corbin LJ, Kranis A, Blott SC, Swinburne JE, Vaudin M, Bishop SC, Woolliams JA. The utility of low-density genotyping for imputation in the Thoroughbred horse. Genet Sel Evol 2014 Feb 4;46(1):9.
                doi: 10.1186/1297-9686-46-9pubmed: 24495673google scholar: lookup
              6. Andersson LS, Wilbe M, Viluma A, Cothran G, Ekesten B, Ewart S, Lindgren G. Equine multiple congenital ocular anomalies and silver coat colour result from the pleiotropic effects of mutant PMEL. PLoS One 2013;8(9):e75639.
                doi: 10.1371/journal.pone.0075639pubmed: 24086599google scholar: lookup
              7. Hellström AR, Watt B, Fard SS, Tenza D, Mannström P, Narfström K, Ekesten B, Ito S, Wakamatsu K, Larsson J, Ulfendahl M, Kullander K, Raposo G, Kerje S, Hallböök F, Marks MS, Andersson L. Inactivation of Pmel alters melanosome shape but has only a subtle effect on visible pigmentation. PLoS Genet 2011 Sep;7(9):e1002285.
                doi: 10.1371/journal.pgen.1002285pubmed: 21949658google scholar: lookup
              8. Andersson LS, Swinburne JE, Meadows JR, Broström H, Eriksson S, Fikse WF, Frey R, Sundquist M, Tseng CT, Mikko S, Lindgren G. The same ELA class II risk factors confer equine insect bite hypersensitivity in two distinct populations. Immunogenetics 2012 Mar;64(3):201-8.
                doi: 10.1007/s00251-011-0573-1pubmed: 21947540google scholar: lookup
              9. Komáromy AM, Rowlan JS, La Croix NC, Mangan BG. Equine Multiple Congenital Ocular Anomalies (MCOA) syndrome in PMEL17 (Silver) mutant ponies: five cases. Vet Ophthalmol 2011 Sep;14(5):313-20.
                doi: 10.1111/j.1463-5224.2011.00878.xpubmed: 21929608google scholar: lookup
              10. Andersson LS, Axelsson J, Dubielzig RR, Lindgren G, Ekesten B. Multiple congenital ocular anomalies in Icelandic horses. BMC Vet Res 2011 May 26;7:21.
                doi: 10.1186/1746-6148-7-21pubmed: 21615885google scholar: lookup
              11. Andersson LS, Lyberg K, Cothran G, Ramsey DT, Juras R, Mikko S, Ekesten B, Ewart S, Lindgren G. Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases. Mamm Genome 2011 Jun;22(5-6):353-60.
                doi: 10.1007/s00335-011-9325-7pubmed: 21465164google scholar: lookup
              12. Brosnahan MM, Brooks SA, Antczak DF. Equine clinical genomics: A clinician's primer. Equine Vet J 2010 Oct;42(7):658-70.
                doi: 10.1111/j.2042-3306.2010.00166.xpubmed: 20840582google scholar: lookup
              13. Webb AA, Cullen CL. Coat color and coat color pattern-related neurologic and neuro-ophthalmic diseases. Can Vet J 2010 Jun;51(6):653-7.
                pubmed: 20808581
              Subscribe to our newsletter
              Join 99,658 horse owners like you who receive our email updates on horse health and nutrition.