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Genomics2007; 90(1); 93-102; doi: 10.1016/j.ygeno.2007.03.009

Homozygosity mapping approach identifies a missense mutation in equine cyclophilin B (PPIB) associated with HERDA in the American Quarter Horse.

Abstract: Hereditary equine regional dermal asthenia (HERDA), a degenerative skin disease that affects the Quarter Horse breed, was localized to ECA1 by homozygosity mapping. Comparative genomics allowed the development of equine gene-specific markers which were used with a set of affected horses to detect a homozygous, identical-by-descent block spanning approximately 2.5 Mb, suggesting a recent origin for the HERDA mutation. We report a mutation in cyclophilin B (PPIB) as a novel, causal candidate gene for HERDA. A c.115G>A missense mutation in PPIB alters a glycine residue that has been conserved across vertebrates. The mutation was homozygous in 64 affected horses and segregates concordant with inbreeding loops apparent in the genealogy of 11 affected horses. Screening of control Quarter Horses indicates a 3.5% carrier frequency. The development of a test that can detect affected horses prior to development of clinical signs and carriers of HERDA will allow Quarter Horse breeders to eliminate this debilitating disease.
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Publication Date: 2007-05-11 PubMed ID: 17498917DOI: 10.1016/j.ygeno.2007.03.009Google 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 article discusses the identification of a particular mutation, namely a missense mutation in the gene equine cyclophilin B (PPIB), which is associated with a debilitating skin disease in Quarter Horses known as Hereditary equine regional dermal asthenia (HERDA). Through a method called homozygosity mapping, scientists were able to locate the mutation, which appears to have a recent origin. The findings pave the way for the development of a test to detect affected horses, which will help curb or eliminate the disease.

Key Findings

  • The research focused on the debilitating skin disease Hereditary equine regional dermal asthenia (HERDA) that affects Quarter Horses. Using a method called homozygosity mapping, which is designed to detect recessive mutations in dogs, they localised the degenerative skin disease to a particular region, ECA1, wherein they found a 2.5 Mb block that appeared to be homozygous and identical by descent (IBD) in affected horses. This indicates a recent origin for the HERDA mutation.
  • They identified a missense mutation, a type of mutation where a single nucleotide change results in a codon that codes for a different amino acid, in the gene equine cyclophilin B (PPIB). This particular mutation changes a glycine residue that is highly conserved across different vertebrates. This strongly suggests that the mutation in PPIB is the primary culprit for HERDA.
  • Screening of a control group of Quarter Horses apparently healthy showed a carrier frequency of 3.5%, signifying that this mutation is relatively common within this breed. As such, a considerable number of Quarter Horses could be quietly carrying the disease, and it can surface at any given moment causing harmful effects.

Implications and Future Directions

  • The identification of the missense mutation in PPIB affords the development of a potential diagnostic tool for HERDA. Equipped with this detection method, breeders would be able to screen their horses for this mutation before they show any signs of the disease. This early detection would prove significantly beneficial as it would allow the implementation of preventive measures to combat the debilitating illness.
  • The results of this research also pave the way to study the disease more closely and understand its exact etiology. This understanding could then be utilized to develop effective treatments and preventive measures, eventually leading to the eradication of the disease from the Quarter Horse breed.

Cite This Article

APA
Tryon RC, White SD, Bannasch DL. (2007). Homozygosity mapping approach identifies a missense mutation in equine cyclophilin B (PPIB) associated with HERDA in the American Quarter Horse. Genomics, 90(1), 93-102. https://doi.org/10.1016/j.ygeno.2007.03.009

Publication

Genomics
ISSN: 0888-7543
NlmUniqueID: 8800135
Country: United States
Language: English
Volume: 90
Issue: 1
Pages: 93-102

Researcher Affiliations

Tryon, Robert C
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA 9516, USA.
White, Stephen D
    Bannasch, Danika L

      MeSH Terms

      • Amino Acid Sequence
      • Animals
      • Asthenia / genetics
      • Asthenia / veterinary
      • Cyclophilins / genetics
      • Genome
      • Homozygote
      • Horse Diseases / genetics
      • Horses / genetics
      • Molecular Sequence Data
      • Mutation, Missense / genetics
      • Pedigree
      • Peptidylprolyl Isomerase / genetics
      • Physical Chromosome Mapping

      Citations

      This article has been cited 32 times.
      1. Stefaniuk-Szmukier M, Błaszczak A, Długosz B, Musiał A, Ropka-Molik K. Surveillance of a PLOD gene variant linked to fragile foal syndrome in Silesian horses in Poland: implications for genetic monitoring and breeding strategies. J Vet Res 2025 Dec;69(4):600-602.
        doi: 10.2478/jvetres-2025-0060pubmed: 41497457google scholar: lookup
      2. Sharif MB, Mohaseb AF, Orlando L, Saliari K, Kunst GK, Czeika S, Mashkour M, Cucchi T, Peters J, Trixl S, Mohandesan E. Late Iron Age and Roman equine breeding north of the Alps: Genetic insights and cultural implications. iScience 2025 Sep 19;28(9):113224.
        doi: 10.1016/j.isci.2025.113224pubmed: 40837235google scholar: lookup
      3. Ishikawa Y, Tufa SF, Keene DR, Bächinger HP, Winand NJ. Biochemical characterization of collagen I in Warmblood Fragile Foal Syndrome horse lysyl hydroxylase 1 mutation. MicroPubl Biol 2025;2025.
        doi: 10.17912/micropub.biology.001399pubmed: 39839713google scholar: lookup
      4. Durward-Akhurst SA, Marlowe JL, Schaefer RJ, Springer K, Grantham B, Carey WK, Bellone RR, Mickelson JR, McCue ME. Predicted genetic burden and frequency of phenotype-associated variants in the horse. Sci Rep 2024 Apr 10;14(1):8396.
        doi: 10.1038/s41598-024-57872-8pubmed: 38600096google scholar: lookup
      5. Grillos AS, Roach JM, de Mestre AM, Foote AK, Kinglsey NB, Mienaltowski MJ, Bellone RR. First reported case of fragile foal syndrome type 1 in the Thoroughbred caused by PLOD1 c.2032G>A. Equine Vet J 2022 Nov;54(6):1086-1093.
        doi: 10.1111/evj.13547pubmed: 34939209google scholar: lookup
      6. Roberts JH, Halper J. Connective Tissue Disorders in Domestic Animals. Adv Exp Med Biol 2021;1348:325-335.
        doi: 10.1007/978-3-030-80614-9_15pubmed: 34807427google scholar: lookup
      7. Vroman R, Malfait AM, Miller RE, Malfait F, Syx D. Animal Models of Ehlers-Danlos Syndromes: Phenotype, Pathogenesis, and Translational Potential. Front Genet 2021;12:726474.
        doi: 10.3389/fgene.2021.726474pubmed: 34712265google scholar: lookup
      8. Rowe Á, Flanagan S, Barry G, Katz LM, Lane EA, Duggan V. Warmblood fragile foal syndrome causative single nucleotide polymorphism frequency in horses in Ireland. Ir Vet J 2021 Oct 18;74(1):27.
        doi: 10.1186/s13620-021-00206-1pubmed: 34663462google scholar: lookup
      9. Reiter S, Wallner B, Brem G, Haring E, Hoelzle L, Stefaniuk-Szmukier M, Długosz B, Piórkowska K, Ropka-Molik K, Malvick J, Penedo MCT, Bellone RR. Distribution of the Warmblood Fragile Foal Syndrome Type 1 Mutation (PLOD1 c.2032G>A) in Different Horse Breeds from Europe and the United States. Genes (Basel) 2020 Dec 18;11(12).
        doi: 10.3390/genes11121518pubmed: 33353040google scholar: lookup
      10. Jacinto JGP, Häfliger IM, Veiga IMB, Letko A, Benazzi C, Bolcato M, Drögemüller C. A Heterozygous Missense Variant in the COL5A2 in Holstein Cattle Resembling the Classical Ehlers-Danlos Syndrome. Animals (Basel) 2020 Oct 30;10(11).
        doi: 10.3390/ani10112002pubmed: 33143196google scholar: lookup
      11. Beeson SK, Mickelson JR, McCue ME. Exploration of fine-scale recombination rate variation in the domestic horse. Genome Res 2019 Oct;29(10):1744-1752.
        doi: 10.1101/gr.243311.118pubmed: 31434677google scholar: lookup
      12. McElroy A, Rashmir A, Manfredi J, Sledge D, Carr E, Stopa E, Klinge P. Evaluation of the Structure of Myodural Bridges in an Equine Model of Ehlers-Danlos Syndromes. Sci Rep 2019 Jul 10;9(1):9978.
        doi: 10.1038/s41598-019-46444-wpubmed: 31292490google scholar: lookup
      13. Terajima M, Taga Y, Cabral WA, Liu Y, Nagasawa M, Sumida N, Kayashima Y, Chandrasekaran P, Han L, Maeda N, Perdivara I, Hattori S, Marini JC, Yamauchi M. Cyclophilin B control of lysine post-translational modifications of skin type I collagen. PLoS Genet 2019 Jun;15(6):e1008196.
        doi: 10.1371/journal.pgen.1008196pubmed: 31173582google scholar: lookup
      14. Burns EN, Bordbari MH, Mienaltowski MJ, Affolter VK, Barro MV, Gianino F, Gianino G, Giulotto E, Kalbfleisch TS, Katzman SA, Lassaline M, Leeb T, Mack M, Müller EJ, MacLeod JN, Ming-Whitfield B, Alanis CR, Raudsepp T, Scott E, Vig S, Zhou H, Petersen JL, Bellone RR, Finno CJ. Generation of an equine biobank to be used for Functional Annotation of Animal Genomes project. Anim Genet 2018 Dec;49(6):564-570.
        doi: 10.1111/age.12717pubmed: 30311254google scholar: lookup
      15. Stokol T. Veterinary Pathology - A Path Forward with New Directions and Opportunities. Front Vet Sci 2016;3:76.
        doi: 10.3389/fvets.2016.00076pubmed: 27630996google scholar: lookup
      16. Heard ME, Besio R, Weis M, Rai J, Hudson DM, Dimori M, Zimmerman SM, Kamykowski JA, Hogue WR, Swain FL, Burdine MS, Mackintosh SG, Tackett AJ, Suva LJ, Eyre DR, Morello R. Sc65-Null Mice Provide Evidence for a Novel Endoplasmic Reticulum Complex Regulating Collagen Lysyl Hydroxylation. PLoS Genet 2016 Apr;12(4):e1006002.
        doi: 10.1371/journal.pgen.1006002pubmed: 27119146google scholar: lookup
      17. Hansen N, Foster SF, Burrows AK, Mackie J, Malik R. Cutaneous asthenia (Ehlers-Danlos-like syndrome) of Burmese cats. J Feline Med Surg 2015 Nov;17(11):954-63.
        doi: 10.1177/1098612X15610683pubmed: 26486982google scholar: lookup
      18. Stefaniuk M, Ropka-Molik K. RNA sequencing as a powerful tool in searching for genes influencing health and performance traits of horses. J Appl Genet 2016 May;57(2):199-206.
        doi: 10.1007/s13353-015-0320-7pubmed: 26446669google scholar: lookup
      19. Jun J, Cho YS, Hu H, Kim HM, Jho S, Gadhvi P, Park KM, Lim J, Paek WK, Han K, Manica A, Edwards JS, Bhak J. Whole genome sequence and analysis of the Marwari horse breed and its genetic origin. BMC Genomics 2014;15 Suppl 9(Suppl 9):S4.
        doi: 10.1186/1471-2164-15-S9-S4pubmed: 25521865google scholar: lookup
      20. Metzger J, Tonda R, Beltran S, Agueda L, Gut M, Distl O. Next generation sequencing gives an insight into the characteristics of highly selected breeds versus non-breed horses in the course of domestication. BMC Genomics 2014 Jul 4;15(1):562.
        doi: 10.1186/1471-2164-15-562pubmed: 24996778google scholar: lookup
      21. Finno CJ, Bannasch DL. Applied equine genetics. Equine Vet J 2014 Sep;46(5):538-44.
        doi: 10.1111/evj.12294pubmed: 24802051google scholar: lookup
      22. Boudko SP, Ishikawa Y, Lerch TF, Nix J, Chapman MS, Bächinger HP. Crystal structures of wild-type and mutated cyclophilin B that causes hyperelastosis cutis in the American quarter horse. BMC Res Notes 2012 Nov 8;5:626.
        doi: 10.1186/1756-0500-5-626pubmed: 23137129google scholar: lookup
      23. Ishikawa Y, Vranka JA, Boudko SP, Pokidysheva E, Mizuno K, Zientek K, Keene DR, Rashmir-Raven AM, Nagata K, Winand NJ, Bächinger HP. Mutation in cyclophilin B that causes hyperelastosis cutis in American Quarter Horse does not affect peptidylprolyl cis-trans isomerase activity but shows altered cyclophilin B-protein interactions and affects collagen folding. J Biol Chem 2012 Jun 22;287(26):22253-65.
        doi: 10.1074/jbc.M111.333336pubmed: 22556420google scholar: lookup
      24. Doan R, Cohen ND, Sawyer J, Ghaffari N, Johnson CD, Dindot SV. Whole-genome sequencing and genetic variant analysis of a Quarter Horse mare. BMC Genomics 2012 Feb 17;13:78.
        doi: 10.1186/1471-2164-13-78pubmed: 22340285google scholar: lookup
      25. 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
      26. Pyott SM, Schwarze U, Christiansen HE, Pepin MG, Leistritz DF, Dineen R, Harris C, Burton BK, Angle B, Kim K, Sussman MD, Weis M, Eyre DR, Russell DW, McCarthy KJ, Steiner RD, Byers PH. Mutations in PPIB (cyclophilin B) delay type I procollagen chain association and result in perinatal lethal to moderate osteogenesis imperfecta phenotypes. Hum Mol Genet 2011 Apr 15;20(8):1595-609.
        doi: 10.1093/hmg/ddr037pubmed: 21282188google scholar: lookup
      27. 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
      28. Brooks SA, Gabreski N, Miller D, Brisbin A, Brown HE, Streeter C, Mezey J, Cook D, Antczak DF. Whole-genome SNP association in the horse: identification of a deletion in myosin Va responsible for Lavender Foal Syndrome. PLoS Genet 2010 Apr 15;6(4):e1000909.
        doi: 10.1371/journal.pgen.1000909pubmed: 20419149google scholar: lookup
      29. Barnes AM, Carter EM, Cabral WA, Weis M, Chang W, Makareeva E, Leikin S, Rotimi CN, Eyre DR, Raggio CL, Marini JC. Lack of cyclophilin B in osteogenesis imperfecta with normal collagen folding. N Engl J Med 2010 Feb 11;362(6):521-8.
        doi: 10.1056/NEJMoa0907705pubmed: 20089953google scholar: lookup
      30. Choi JW, Sutor SL, Lindquist L, Evans GL, Madden BJ, Bergen HR 3rd, Hefferan TE, Yaszemski MJ, Bram RJ. Severe osteogenesis imperfecta in cyclophilin B-deficient mice. PLoS Genet 2009 Dec;5(12):e1000750.
        doi: 10.1371/journal.pgen.1000750pubmed: 19997487google scholar: lookup
      31. Chang W, Barnes AM, Cabral WA, Bodurtha JN, Marini JC. Prolyl 3-hydroxylase 1 and CRTAP are mutually stabilizing in the endoplasmic reticulum collagen prolyl 3-hydroxylation complex. Hum Mol Genet 2010 Jan 15;19(2):223-34.
        doi: 10.1093/hmg/ddp481pubmed: 19846465google scholar: lookup
      32. Chowdhary BP, Raudsepp T. The horse genome derby: racing from map to whole genome sequence. Chromosome Res 2008;16(1):109-27.
        doi: 10.1007/s10577-008-1204-zpubmed: 18274866google scholar: lookup
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