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Mammalian genome : official journal of the International Mammalian Genome Society2011; 22(5-6); 353-360; doi: 10.1007/s00335-011-9325-7

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

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.
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Publication Date: 2011-04-05 PubMed ID: 21465164PubMed Central: PMC3098992DOI: 10.1007/s00335-011-9325-7Google Scholar: Lookup
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  • Comparative Study
  • 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.

This research focuses on the heritable eye disorder in horses known as Multiple Congenital Ocular Anomalies (MCOA). Using genetic mapping, the researchers have narrowed down the locations on the genetic code where this disorder might originate. This information can help breeders maintain desirable traits in horses while avoiding the health issues associated with the MCOA disorder.

Understanding MCOA in Horses

  • MCOA, or Multiple Congenital Ocular Anomalies, is a genetically inherited eye disorder in horses with symptoms including a wide range of eye anomalies. Homozygous horses (those with two identical alleles for the disease) exhibit this syndrome, while heterozygous horses (those with differing alleles) tend to show only the cyst-forming attributes of the disease.
  • This disorder is known to occur most frequently in the Rocky Mountain Horse breed, but it’s not exclusive to them. Horses carrying this disease often exhibit a Silver coat color, though a definitive link between the coat color and the disease hasn’t been found.

Genetic Mapping of MCOA

  • The researchers utilized a technique called identical-by-descent mapping to find the location of the MCOA genetic component on a horse’s chromosome. This allowed them to narrow down the previously known 4.6-Mb region to a 264-kb segment on the chromosome where the MCOA gene can be found.
  • This smaller section of genes isn’t just found in Rocky Mountain Horses, but also in three other breeds, helping to confirm its link to the disease.

Narrowing Down the MCOA Locus

  • The researchers further investigated and screened the genes found within the 264-kb region and found two specific candidate genes: SMARCC2 and IKZF4. Genotyping and segregation analysis of these genes allowed them to shrink the suspected cause for the MCOA syndrome down to an even smaller 208-kb region on the horse’s chromosome.
  • The researchers note that this narrowed-down region also contains PMEL17, the gene responsible for the Silver coat color in horses. This made it a viable candidate for further scrutiny given the commonly observed link between the MCOA syndrome and Silver coat color in affected horses.
  • By successfully narrowing down the suspected area for MCOA syndrome within the horse’s chromosome, the researchers were able to disassociate 176 other genes from the disease. Now only 15 genes, including PMEL17, remain linked to the disease. This offers a more specialized area for future research in better understanding and dealing with MCOA syndrome in horses.

Cite This Article

APA
Andersson LS, Lyberg K, Cothran G, Ramsey DT, Juras R, Mikko S, Ekesten B, Ewart S, Lindgren G. (2011). Targeted analysis of four breeds narrows equine Multiple Congenital Ocular Anomalies locus to 208 kilobases. Mamm Genome, 22(5-6), 353-360. https://doi.org/10.1007/s00335-011-9325-7

Publication

Mammalian genome : official journal of the International Mammalian Genome Society
ISSN: 1432-1777
NlmUniqueID: 9100916
Country: United States
Language: English
Volume: 22
Issue: 5-6
Pages: 353-360

Researcher Affiliations

Andersson, Lisa S
  • Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Undervisningsplan 4A, PO Box 7023, 750 07 Uppsala, Sweden.
Lyberg, Katarina
    Cothran, Gus
      Ramsey, David T
        Juras, Rytis
          Mikko, Sofia
            Ekesten, Björn
              Ewart, Susan
                Lindgren, Gabriella

                  MeSH Terms

                  • Animals
                  • Base Sequence
                  • Chromosome Mapping
                  • Chromosomes, Mammalian / genetics
                  • Eye Abnormalities / genetics
                  • Eye Abnormalities / veterinary
                  • Genetic Loci / genetics
                  • Genotype
                  • Haplotypes / genetics
                  • Horse Diseases / genetics
                  • Horses
                  • Microsatellite Repeats / genetics
                  • Molecular Sequence Data
                  • Polymorphism, Single Nucleotide / genetics
                  • Sequence Analysis, DNA
                  • Species Specificity
                  • Syndrome
                  • Transcription Factors / genetics

                  References

                  This article includes 35 references
                  1. Andersson LS, Juras R, Ramsey DT, Eason-Butler J, Ewart S, Cothran G, Lindgren G. Equine Multiple Congenital Ocular Anomalies maps to a 4.9 megabase interval on horse chromosome 6.. BMC Genet 2008;9:88.
                    doi: 10.1186/1471-2156-9-88pmc: PMC2653074pubmed: 19099555google scholar: lookup
                  2. Benson G. Tandem repeats finder: a program to analyze DNA sequences.. Nucleic Acids Res 1999;27(2):573–580.
                    doi: 10.1093/nar/27.2.573pmc: PMC148217pubmed: 9862982google scholar: lookup
                  3. 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
                  4. 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(5):1376–1381.
                    doi: 10.1073/pnas.0506940103pmc: PMC1360527pubmed: 16407134google scholar: lookup
                  5. Corbeel L, Freson K. Rab proteins and Rab-associated proteins: major actors in the mechanism of protein-trafficking disorders.. Eur J Pediatr 2008;167(7):723–729.
                    doi: 10.1007/s00431-008-0740-zpmc: PMC2413085pubmed: 18463892google scholar: lookup
                  6. Das AV, James J, Bhattacharya S, Imbalzano AN, Antony ML, Hegde G, Zhao X, Mallya K, Ahmad F, Knudsen E, Ahmad I. SWI/SNF chromatin remodeling ATPase Brm regulates the differentiation of early retinal stem cells/progenitors by influencing Brn3b expression and Notch signaling.. J Biol Chem 2007;282(48):35187–35201.
                    doi: 10.1074/jbc.M706742200pubmed: 17855369google scholar: lookup
                  7. Dechassa ML, Zhang B, Horowitz-Scherer R, Persinger J, Woodcock CL, Peterson CL, Bartholomew B. Architecture of the SWI/SNF–nucleosome complex.. Mol Cell Biol 2008;28(19):6010–6021.
                    doi: 10.1128/MCB.00693-08pmc: PMC2547009pubmed: 18644858google scholar: lookup
                  8. Duncan B, Zhao K. HMGA1 mediates the activation of the CRYAB promoter by BRG1.. DNA Cell Biol 2007;26(10):745–752.
                    doi: 10.1089/dna.2007.0629pubmed: 17723105google 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(2):93–98.
                    doi: 10.1093/jhered/91.2.93pubmed: 10768120google scholar: lookup
                  10. 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(7):675–681.
                    pmc: PMC2430397pubmed: 18827844
                  11. Hodgkinson CA, Moore KJ, Nakayama A, Steingrímsson E, Copeland NG, Jenkins NA, Arnheiter H. Mutations at the mouse microphthalmia locus are associated with defects in a gene encoding a novel basic-helix-loop-helix-zipper protein.. Cell 1993;74(2):395–404.
                    doi: 10.1016/0092-8674(93)90429-Tpubmed: 8343963google scholar: lookup
                  12. Hu R, Sharma SM, Bronisz A, Srinivasan R, Sankar U, Ostrowski MC. Eos, MITF, and PU.1 recruit corepressors to osteoclast-specific genes in committed myeloid progenitors.. Mol Cell Biol 2007;27(11):4018–4027.
                    doi: 10.1128/MCB.01839-06pmc: PMC1900027pubmed: 17403896google scholar: lookup
                  13. Johnson JL, Rajagopalan KV, Renier WO, Van der Burgt I, Ruitenbeek W. Isolated sulfite oxidase deficiency: mutation analysis and DNA-based prenatal diagnosis.. Prenat Diagn 2002;22(5):433–436.
                    doi: 10.1002/pd.335pubmed: 12001203google scholar: lookup
                  14. Karlsson AC, Kerje S, Hallbook F, Jensen P. The Dominant white mutation in the PMEL17 gene does not cause visual impairment in chickens.. Vet Ophthalmol 2009;12(5):292–298.
                    doi: 10.1111/j.1463-5224.2009.00714.xpubmed: 19751488google scholar: lookup
                  15. Kerje S, Sharma P, Gunnarsson U, Kim H, Bagchi S, Fredriksson R, Schutz K, Jensen P, von Heijne G, Okimoto R, Andersson L. The Dominant white, Dun and Smoky color variants in chicken are associated with insertion/deletion polymorphisms in the PMEL17 gene.. Genetics 2004;168(3):1507–1518.
                    doi: 10.1534/genetics.104.027995pmc: PMC1448810pubmed: 15579702google scholar: lookup
                  16. Komaromy A, Rowlan JS. Multiple congenital ocular abnormalities (MCOA) syndrome in two silver coat colored ponies.. Proc Am Coll Vet Ophthalmol 2009;40:113.
                  17. Kuehn C, Weikard R. Multiple splice variants within the bovine silver homologue (SILV) gene affecting coat color in cattle indicate a function additional to fibril formation in melanophores.. BMC Genomics 2007;8:335.
                    doi: 10.1186/1471-2164-8-335pmc: PMC2099443pubmed: 17892572google scholar: lookup
                  18. Kwon BS, Halaban R, Ponnazhagan S, Kim K, Chintamaneni C, Bennett D, Pickard RT. Mouse silver mutation is caused by a single base insertion in the putative cytoplasmic domain of Pmel17.. Nucleic Acids Res 1995;23(1):154–158.
                    doi: 10.1093/nar/23.1.154pmc: PMC306643pubmed: 7870580google scholar: lookup
                  19. Liu Z, Carvajal M, Carothers Carraway CA, Carraway KL, Pflugfelder SC. Increased expression of the type 1 growth factor receptor family in the conjunctival epithelium of patients with keratoconjunctivitis sicca.. Am J Ophthalmol 2000;129(4):472–480.
                    doi: 10.1016/S0002-9394(99)00407-9pubmed: 10764856google scholar: lookup
                  20. Liu R, Liu H, Chen X, Kirby M, Brown PO, Zhao K. Regulation of CSF1 promoter by the SWI/SNF-like BAF complex.. Cell 2001;106(3):309–318.
                    doi: 10.1016/S0092-8674(01)00446-9pubmed: 11509180google scholar: lookup
                  21. Nobukuni Y, Watanabe A, Takeda K, Skarka H, Tachibana M. Analyses of loss-of-function mutations of the MITF gene suggest that haploinsufficiency is a cause of Waardenburg syndrome type 2A.. Am J Hum Genet 1996;59(1):76–83.
                    pmc: PMC1915102pubmed: 8659547
                  22. Ramsey DT, Ewart SL, Render JA, Cook CS, Latimer CA. Congenital ocular abnormalities of Rocky Mountain horses.. Vet Ophthalmol 1999;2(1):47–59.
                    doi: 10.1046/j.1463-5224.1999.00050.xpubmed: 11397242google scholar: lookup
                  23. 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(10):1317–1321.
                    pubmed: 10791948
                  24. Ramsey DT, Mutti DO, Zadnik C, Bullimore MA, Murphy CJ. Refractive error in Rocky Mountain horses with cornea globosa and with normal corneas.. Invest Ophthalmol Vis Sci 2000;41(4):S135.
                  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. 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(3):241–250.
                    doi: 10.1111/j.1365-2052.1992.tb00136.xpubmed: 1323940google scholar: lookup
                  27. Santschi EM, Purdy AK, Valberg SJ, Vrotsos PD, Kaese H, Mickelson JR. Endothelin receptor B polymorphism associated with lethal white foal syndrome in horses.. Mamm Genome 1998;9(4):306–309.
                    doi: 10.1007/s003359900754pubmed: 9530628google scholar: lookup
                  28. 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(2):421–436.
                    doi: 10.1016/j.ydbio.2005.06.001pubmed: 16024012google scholar: lookup
                  29. 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(8):3565–3569.
                    pubmed: 9103416
                  30. Theos AC, Truschel ST, Raposo G, Marks MS. The Silver locus product Pmel17/gp100/Silv/ME20: controversial in name and in function.. Pigment Cell Res 2005;18(5):322–336.
                    doi: 10.1111/j.1600-0749.2005.00269.xpmc: PMC2788625pubmed: 16162173google scholar: lookup
                  31. Thierry-Mieg D, Thierry-Mieg J. AceView: a comprehensive cDNA-supported gene and transcripts annotation.. Genome Biol 2006;7 Suppl 1:S12.1–14.
                    pmc: PMC1810549pubmed: 16925834
                  32. Tryon RC, White SD, Bannasch DL. Homozygosity mapping approach identifies a missense mutation in equine cyclophilin B (PPIB) associated with HERDA in the American Quarter Horse.. Genomics 2007;90(1):93–102.
                    doi: 10.1016/j.ygeno.2007.03.009pubmed: 17498917google scholar: lookup
                  33. Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F, Lear TL, Adelson DL, Bailey E, Bellone RR, Blocker H, Distl O, Edgar RC, Garber M, Leeb T, Mauceli E, MacLeod JN, Penedo MC, Raison JM, Sharpe T, Vogel J, Andersson L, Antczak DF, Biagi T, Binns MM, Chowdhary BP, Coleman SJ, Della Valle G, Fryc S, Guerin G, Hasegawa T, Hill EW, Jurka J, Kiialainen A, Lindgren G, Liu J, Magnani E, Mickelson JR, Murray J, Nergadze SG, Onofrio R, Pedroni S, Piras MF, Raudsepp T, Rocchi M, Roed KH, Ryder OA, Searle S, Skow L, Swinburne JE, Syvanen AC, Tozaki T, Valberg SJ, Vaudin M, White JR, Zody MC, Lander ES, Lindblad-Toh K. Genome sequence, comparative analysis, and population genetics of the domestic horse.. Science 2009;326(5954):865–867.
                    doi: 10.1126/science.1178158pmc: PMC3785132pubmed: 19892987google scholar: lookup
                  34. Wang L, Wormstone IM, Reddan JR, Duncan G. Growth factor receptor signalling in human lens cells: role of the calcium store.. Exp Eye Res 2005;80(6):885–895.
                    doi: 10.1016/j.exer.2005.01.002pubmed: 15939046google scholar: lookup
                  35. Watanabe A, Takeda K, Ploplis B, Tachibana M. Epistatic relationship between Waardenburg syndrome genes MITF and PAX3.. Nat Genet 1998;18(3):283–286.
                    doi: 10.1038/ng0398-283pubmed: 9500554google scholar: lookup

                  Citations

                  This article has been cited 3 times.
                  1. Le L, Sirés-Campos J, Raposo G, Delevoye C, Marks MS. Melanosome Biogenesis in the Pigmentation of Mammalian Skin. Integr Comp Biol 2021 Oct 14;61(4):1517-1545.
                    doi: 10.1093/icb/icab078pubmed: 34021746google scholar: lookup
                  2. 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
                  3. 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
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