FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
G3 (Bethesda, Md.)2022; 12(10); jkac179; doi: 10.1093/g3journal/jkac179

Selection signature analyses and genome-wide association reveal genomic hotspot regions that reflect differences between breeds of horse with contrasting risk of degenerative suspensory ligament desmitis.

Abstract: Degenerative suspensory ligament desmitis is a progressive idiopathic condition that leads to scarring and rupture of suspensory ligament fibers in multiple limbs in horses. The prevalence of degenerative suspensory ligament desmitis is breed related. Risk is high in the Peruvian Horse, whereas pony and draft breeds have low breed risk. Degenerative suspensory ligament desmitis occurs in families of Peruvian Horses, but its genetic architecture has not been definitively determined. We investigated contrasts between breeds with differing risk of degenerative suspensory ligament desmitis and identified associated risk variants and candidate genes. We analyzed 670k single nucleotide polymorphisms from 10 breeds, each of which was assigned one of the four breed degenerative suspensory ligament desmitis risk categories: control (Belgian, Icelandic Horse, Shetland Pony, and Welsh Pony), low risk (Lusitano, Arabian), medium risk (Standardbred, Thoroughbred, Quarter Horse), and high risk (Peruvian Horse). Single nucleotide polymorphisms were used for genome-wide association and selection signature analysis using breed-assigned risk levels. We found that the Peruvian Horse is a population with low effective population size and our breed contrasts suggest that degenerative suspensory ligament desmitis is a polygenic disease. Variant frequency exhibited signatures of positive selection across degenerative suspensory ligament desmitis breed risk groups on chromosomes 7, 18, and 23. Our results suggest degenerative suspensory ligament desmitis breed risk is associated with disturbances to suspensory ligament homeostasis where matrix responses to mechanical loading are perturbed through disturbances to aging in tendon (PIN1), mechanotransduction (KANK1, KANK2, JUNB, SEMA7A), collagen synthesis (COL4A1, COL5A2, COL5A3, COL6A5), matrix responses to hypoxia (PRDX2), lipid metabolism (LDLR, VLDLR), and BMP signaling (GREM2). Our results do not suggest that suspensory ligament proteoglycan turnover is a primary factor in disease pathogenesis.
© The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.
Get Full Text
Publication Date: 2022-07-23 PubMed ID: 35866615PubMed Central: PMC9526059DOI: 10.1093/g3journal/jkac179Google 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
  • N.I.H.
  • Extramural

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 researchers studied the genetic factors contributing to a horse disease called degenerative suspensory ligament desmitis and found certain gene variants associated with a higher risk of the disease, particularly in the Peruvian horse breed.

Research Context

  • The research focused on degenerative suspensory ligament desmitis (DSLD), a disease that damages the suspensory ligaments in horse legs leading to lameness. The occurrence of this disease is discovered to be breed-specific, making it prevalent amongst Peruvian Horses and scarce in pony and draft breeds.
  • The disease is known to occur in families of Peruvian Horses, implying possible genetic factors.
  • DSLD’s exact genetic composition remained undefined before this study, making it the researchers’ primary objective.

Methodology

  • The study was conducted analyzing 670k single nucleotide polymorphisms (SNPs), variations at a single position in a DNA sequence, across 10 horse breeds. The breeds were categorized according to their risk of developing DSLD: control, low risk, medium risk, and high risk.
  • The researchers used these SNPs for a genome-wide association and selection signature analysis, utilizing the assigned breed risk levels.

Key Findings

  • Peruvian Horse, a breed with a high risk of DSLD, was found to have a low effective population size, implying that this breed has less genetic diversity.
  • DSLD was identified as a polygenic disease, meaning it is influenced by multiple genes.
  • The study identified potential disease-related SNPs on chromosomes 7, 18, and 23, showing signs of positive selection, meaning these variations were advantageous due to the influence of natural selection.
  • The genetic variants suggested a disturbance in the homeostasis of the suspensory ligament, affecting numerous functions such as collagen synthesis, lipid metabolism, aging in tendon, matrix responses to mechanical loading and hypoxia, and BMP signaling.
  • Proteoglycan turnover in suspensory ligament, however, was not implicated as a significant factor in the disease’s development.

Implications

  • The findings provide a better understanding of the genetic architecture of DSLD, paving the way for further research into prevention and treatment measures.
  • The study also offers valuable insights into how genetic factors can contribute to breed-specific diseases in horses, highlighting the importance of genetic diversity.

Cite This Article

APA
Momen M, Brounts SH, Binversie EE, Sample SJ, Rosa GJM, Davis BW, Muir P. (2022). Selection signature analyses and genome-wide association reveal genomic hotspot regions that reflect differences between breeds of horse with contrasting risk of degenerative suspensory ligament desmitis. G3 (Bethesda), 12(10), jkac179. https://doi.org/10.1093/g3journal/jkac179

Publication

G3 (Bethesda, Md.)
ISSN: 2160-1836
NlmUniqueID: 101566598
Country: England
Language: English
Volume: 12
Issue: 10
PII: jkac179

Researcher Affiliations

Momen, Mehdi
  • Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Brounts, Sabrina H
  • Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Binversie, Emily E
  • Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Sample, Susannah J
  • Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Rosa, Guilherme J M
  • Department of Animal and Dairy Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA.
Davis, Brian W
  • Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
Muir, Peter
  • Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.

MeSH Terms

  • Animals
  • Genome-Wide Association Study
  • Genomics
  • Horse Diseases / genetics
  • Horse Diseases / pathology
  • Horses / genetics
  • Ligaments / metabolism
  • Ligaments / pathology
  • Mechanotransduction, Cellular
  • Muscular Diseases / metabolism
  • Proteoglycans / metabolism

Grant Funding

  • R21 AR073301 / NIAMS NIH HHS
  • T15 LM007359 / NLM NIH HHS
  • T32 OD010423 / NIH HHS

References

This article includes 95 references
  1. Ablondi M, Dadousis C, Vasini M, Eriksson S, Mikko S, Sabbioni A. Genetic Diversity and Signatures of Selection in a Native Italian Horse Breed Based on SNP Data.. Animals (Basel) 2020 Jun 8;10(6).
    pmc: PMC7341496pubmed: 32521830doi: 10.3390/ani10061005google scholar: lookup
  2. Alexander DH, Novembre J, Lange K. Fast model-based estimation of ancestry in unrelated individuals.. Genome Res 2009 Sep;19(9):1655-64.
    pmc: PMC2752134pubmed: 19648217doi: 10.1101/gr.094052.109google scholar: lookup
  3. Alexander D, Shringarpure S, Novembre J, Lange K. ADMIXTURE Version 1.3.0; [Internet]. https://dalexander.github.io/admixture/.
  4. Aljenedil S, Ruel I, Watters K, Genest J. Severe xanthomatosis in heterozygous familial hypercholesterolemia.. J Clin Lipidol 2018 Jul-Aug;12(4):872-877.
    pubmed: 29778561doi: 10.1016/j.jacl.2018.03.087google scholar: lookup
  5. Bancelin S, Lynch B, Bonod-Bidaud C, Ducourthial G, Psilodimitrakopoulos S, Dokládal P, Allain JM, Schanne-Klein MC, Ruggiero F. Ex vivo multiscale quantitation of skin biomechanics in wild-type and genetically-modified mice using multiphoton microscopy.. Sci Rep 2015 Dec 3;5:17635.
    pmc: PMC4668561pubmed: 26631592doi: 10.1038/srep17635google scholar: lookup
  6. Barbato M, Orozco-terWengel P, Tapio M, Bruford MW. SNeP: a tool to estimate trends in recent effective population size trajectories using genome-wide SNP data.. Front Genet 2015;6:109.
    pmc: PMC4367434pubmed: 25852748doi: 10.3389/fgene.2015.00109google scholar: lookup
  7. 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.
    pmc: PMC6771410pubmed: 31434677doi: 10.1101/gr.243311.118google scholar: lookup
  8. Bittermann A, Gao S, Rezvani S, Li J, Sikes KJ, Sandy J, Wang V, Lee S, Holmes G, Lin J, Plaas A. Oral Ibuprofen Interferes with Cellular Healing Responses in a Murine Model of Achilles Tendinopathy.. J Musculoskelet Disord Treat 2018;4(2).
    pmc: PMC6347402pubmed: 30687812doi: 10.23937/2572-3243.1510049google scholar: lookup
  9. Casper J, Zweig AS, Villarreal C, Tyner C, Speir ML, Rosenbloom KR, Raney BJ, Lee CM, Lee BT, Karolchik D, Hinrichs AS, Haeussler M, Guruvadoo L, Navarro Gonzalez J, Gibson D, Fiddes IT, Eisenhart C, Diekhans M, Clawson H, Barber GP, Armstrong J, Haussler D, Kuhn RM, Kent WJ. The UCSC Genome Browser database: 2018 update.. Nucleic Acids Res 2018 Jan 4;46(D1):D762-D769.
    pmc: PMC5753355pubmed: 29106570doi: 10.1093/nar/gkx1020google scholar: lookup
  10. Chang CC, Chow CC, Tellier LC, Vattikuti S, Purcell SM, Lee JJ. Second-generation PLINK: rising to the challenge of larger and richer datasets.. Gigascience 2015;4:7.
    pmc: PMC4342193pubmed: 25722852doi: 10.1186/s13742-015-0047-8google scholar: lookup
  11. Chen L, Liu J, Tao X, Wang G, Wang Q, Liu X. The role of Pin1 protein in aging of human tendon stem/progenitor cells.. Biochem Biophys Res Commun 2015 Aug 21;464(2):487-92.
    pubmed: 26150353doi: 10.1016/j.bbrc.2015.06.163google scholar: lookup
  12. Chiarelli N, Carini G, Zoppi N, Ritelli M, Colombi M. Molecular insights in the pathogenesis of classical Ehlers-Danlos syndrome from transcriptome-wide expression profiling of patients' skin fibroblasts.. PLoS One 2019;14(2):e0211647.
    pmc: PMC6361458pubmed: 30716086doi: 10.1371/journal.pone.0211647google scholar: lookup
  13. Chu KL, Lew QJ, Rajasegaran V, Kung JT, Zheng L, Yang Q, Shaw R, Cheong N, Liou YC, Chao SH. Regulation of PRDX1 peroxidase activity by Pin1.. Cell Cycle 2013 Mar 15;12(6):944-52.
    pmc: PMC3637353pubmed: 23421996doi: 10.4161/cc.23916google scholar: lookup
  14. Cosgrove EJ, Sadeghi R, Schlamp F, Holl HM, Moradi-Shahrbabak M, Miraei-Ashtiani SR, Abdalla S, Shykind B, Troedsson M, Stefaniuk-Szmukier M, Prabhu A, Bucca S, Bugno-Poniewierska M, Wallner B, Malek J, Miller DC, Clark AG, Antczak DF, Brooks SA. Genome Diversity and the Origin of the Arabian Horse.. Sci Rep 2020 Jun 16;10(1):9702.
    pmc: PMC7298027pubmed: 32546689doi: 10.1038/s41598-020-66232-1google scholar: lookup
  15. Cutter AD, Payseur BA. Genomic signatures of selection at linked sites: unifying the disparity among species.. Nat Rev Genet 2013 Apr;14(4):262-74.
    pmc: PMC4066956pubmed: 23478346doi: 10.1038/nrg3425google scholar: lookup
  16. Dai GC, Li YJ, Chen MH, Lu PP, Rui YF. Tendon stem/progenitor cell ageing: Modulation and rejuvenation.. World J Stem Cells 2019 Sep 26;11(9):677-692.
    pmc: PMC6789185pubmed: 31616543doi: 10.4252/wjsc.v11.i9.677google scholar: lookup
  17. Dandine-Roulland C, Perdry H. Genome-wide data manipulation, association analysis, and heritability estimates in R with Gaston 1.5. Human Hered 2017;83:6.
  18. Danecek P, Auton A, Abecasis G, Albers CA, Banks E, DePristo MA, Handsaker RE, Lunter G, Marth GT, Sherry ST, McVean G, Durbin R. The variant call format and VCFtools.. Bioinformatics 2011 Aug 1;27(15):2156-8.
    pmc: PMC3137218pubmed: 21653522doi: 10.1093/bioinformatics/btr330google scholar: lookup
  19. de Simoni Gouveia JJ, da Silva MV, Paiva SR, de Oliveira SM. Identification of selection signatures in livestock species.. Genet Mol Biol 2014 Jun;37(2):330-42.
    pmc: PMC4094609pubmed: 25071397doi: 10.1590/s1415-47572014000300004google scholar: lookup
  20. Doherty A, Lopes I, Ford CT, Monaco G, Guest P, de Magalhães JP. A scan for genes associated with cancer mortality and longevity in pedigree dog breeds.. Mamm Genome 2020 Aug;31(7-8):215-227.
    pmc: PMC7496057pubmed: 32661568doi: 10.1007/s00335-020-09845-1google scholar: lookup
  21. Fariello MI, Boitard S, Naya H, SanCristobal M, Servin B. Detecting signatures of selection through haplotype differentiation among hierarchically structured populations.. Genetics 2013 Mar;193(3):929-41.
    pmc: PMC3584007pubmed: 23307896doi: 10.1534/genetics.112.147231google scholar: lookup
  22. Felsenstein J. PHYLIP (Phylogeny Inference Package). Version 3.5c. Joseph Felsenstein; 1993.
  23. Frankham RC, Bradshaw JA, Brook BW. Genetics in conservation management: revised recommendations for the 50/500 rules, red list criteria and population viability analyses. Biol Conserv 2014;170:56–63.
  24. Gee HY, Zhang F, Ashraf S, Kohl S, Sadowski CE, Vega-Warner V, Zhou W, Lovric S, Fang H, Nettleton M, Zhu JY, Hoefele J, Weber LT, Podracka L, Boor A, Fehrenbach H, Innis JW, Washburn J, Levy S, Lifton RP, Otto EA, Han Z, Hildebrandt F. KANK deficiency leads to podocyte dysfunction and nephrotic syndrome.. J Clin Invest 2015 Jun;125(6):2375-84.
    pmc: PMC4497755pubmed: 25961457doi: 10.1172/jci79504google scholar: lookup
  25. Gianola D. Theory and analysis of threshold characters. J. Anim. Sci. 1982;54(5):1079–1096.
  26. Gossmann TI, Keightley PD, Eyre-Walker A. The effect of variation in the effective population size on the rate of adaptive molecular evolution in eukaryotes.. Genome Biol Evol 2012;4(5):658-67.
    pmc: PMC3381672pubmed: 22436998doi: 10.1093/gbe/evs027google scholar: lookup
  27. Guiraud S, Migeon T, Ferry A, Chen Z, Ouchelouche S, Verpont MC, Sado Y, Allamand V, Ronco P, Plaisier E. HANAC Col4a1 Mutation in Mice Leads to Skeletal Muscle Alterations due to a Primary Vascular Defect.. Am J Pathol 2017 Mar;187(3):505-516.
    pmc: PMC5389361pubmed: 28056338doi: 10.1016/j.ajpath.2016.10.020google scholar: lookup
  28. Gurgul A, Jasielczuk I, Semik-Gurgul E, Pawlina-Tyszko K, Stefaniuk-Szmukier M, Szmatoła T, Polak G, Tomczyk-Wrona I, Bugno-Poniewierska M. A genome-wide scan for diversifying selection signatures in selected horse breeds.. PLoS One 2019;14(1):e0210751.
    pmc: PMC6353161pubmed: 30699152doi: 10.1371/journal.pone.0210751google scholar: lookup
  29. Halper J, Kim B, Khan A, Yoon JH, Mueller PO. Degenerative suspensory ligament desmitis as a systemic disorder characterized by proteoglycan accumulation.. BMC Vet Res 2006 Apr 12;2:12.
    pmc: PMC1459153pubmed: 16611357doi: 10.1186/1746-6148-2-12google scholar: lookup
  30. Halper J, Khan A, Mueller POE. Degenerative suspensory ligament desmitis—a new reality. Pakistan Vet J 2011;31(1):1–8.
  31. Haythorn A, Young M, Stanton J, Zhang J, Mueller POE, Halper J. Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis.. J Orthop Surg Res 2020 Oct 7;15(1):460.
    pmc: PMC7541307pubmed: 33028365doi: 10.1186/s13018-020-01994-ygoogle scholar: lookup
  32. Imamura Y, Scott IC, Greenspan DS. The pro-alpha3(V) collagen chain. Complete primary structure, expression domains in adult and developing tissues, and comparison to the structures and expression domains of the other types V and XI procollagen chains.. J Biol Chem 2000 Mar 24;275(12):8749-59.
    pubmed: 10722718doi: 10.1074/jbc.275.12.8749google scholar: lookup
  33. Jacobson KR, Lipp S, Acuna A, Leng Y, Bu Y, Calve S. Comparative Analysis of the Extracellular Matrix Proteome across the Myotendinous Junction.. J Proteome Res 2020 Oct 2;19(10):3955-3967.
    pmc: PMC8325396pubmed: 32830507doi: 10.1021/acs.jproteome.0c00248google scholar: lookup
  34. Jeong SJ, Kim S, Park JG, Jung IH, Lee MN, Jeon S, Kweon HY, Yu DY, Lee SH, Jang Y, Kang SW, Han KH, Miller YI, Park YM, Cheong C, Choi JH, Oh GT. Prdx1 (peroxiredoxin 1) deficiency reduces cholesterol efflux via impaired macrophage lipophagic flux.. Autophagy 2018;14(1):120-133.
    pmc: PMC5846566pubmed: 28605287doi: 10.1080/15548627.2017.1327942google scholar: lookup
  35. Johnston JM, Connizzo BK, Shetye SS, Robinson KA, Huegel J, Rodriguez AB, Sun M, Adams SM, Birk DE, Soslowsky LJ. Collagen V haploinsufficiency in a murine model of classic Ehlers-Danlos syndrome is associated with deficient structural and mechanical healing in tendons.. J Orthop Res 2017 Dec;35(12):2707-2715.
    pmc: PMC5632109pubmed: 28387435doi: 10.1002/jor.23571google scholar: lookup
  36. Kakinuma N, Roy BC, Zhu Y, Wang Y, Kiyama R. Kank regulates RhoA-dependent formation of actin stress fibers and cell migration via 14-3-3 in PI3K-Akt signaling.. J Cell Biol 2008 May 5;181(3):537-49.
    pmc: PMC2364698pubmed: 18458160doi: 10.1083/jcb.200707022google scholar: lookup
  37. Kalbfleisch TS, Rice ES, DePriest MS Jr, Walenz BP, Hestand MS, Vermeesch JR, O Connell BL, Fiddes IT, Vershinina AO, Saremi NF, Petersen JL, Finno CJ, Bellone RR, McCue ME, Brooks SA, Bailey E, Orlando L, Green RE, Miller DC, Antczak DF, MacLeod JN. Improved reference genome for the domestic horse increases assembly contiguity and composition.. Commun Biol 2018;1:197.
    pmc: PMC6240028pubmed: 30456315doi: 10.1038/s42003-018-0199-zgoogle scholar: lookup
  38. Kang HR, Lee CG, Homer RJ, Elias JA. Semaphorin 7A plays a critical role in TGF-beta1-induced pulmonary fibrosis.. J Exp Med 2007 May 14;204(5):1083-93.
    pmc: PMC2118575pubmed: 17485510doi: 10.1084/jem.20061273google scholar: lookup
  39. Karlsson EK, Sigurdsson S, Ivansson E, Thomas R, Elvers I, Wright J, Howald C, Tonomura N, Perloski M, Swofford R, Biagi T, Fryc S, Anderson N, Courtay-Cahen C, Youell L, Ricketts SL, Mandlebaum S, Rivera P, von Euler H, Kisseberth WC, London CA, Lander ES, Couto G, Comstock K, Starkey MP, Modiano JF, Breen M, Lindblad-Toh K. Genome-wide analyses implicate 33 loci in heritable dog osteosarcoma, including regulatory variants near CDKN2A/B.. Genome Biol 2013 Dec 12;14(12):R132.
    pmc: PMC4053774pubmed: 24330828doi: 10.1186/gb-2013-14-12-r132google scholar: lookup
  40. Kemper KE, Saxton SJ, Bolormaa S, Hayes BJ, Goddard ME. Selection for complex traits leaves little or no classic signatures of selection.. BMC Genomics 2014 Mar 28;15(1):246.
    pmc: PMC3986643pubmed: 24678841doi: 10.1186/1471-2164-15-246google scholar: lookup
  41. Laity JH, Lee BM, Wright PE. Zinc finger proteins: new insights into structural and functional diversity.. Curr Opin Struct Biol 2001 Feb;11(1):39-46.
    pubmed: 11179890doi: 10.1016/s0959-440x(00)00167-6google scholar: lookup
  42. Lamandé SR, Bateman JF. Collagen VI disorders: Insights on form and function in the extracellular matrix and beyond.. Matrix Biol 2018 Oct;71-72:348-367.
    pubmed: 29277723doi: 10.1016/j.matbio.2017.12.008google scholar: lookup
  43. Lawson DJ, van Dorp L, Falush D. A tutorial on how not to over-interpret STRUCTURE and ADMIXTURE bar plots.. Nat Commun 2018 Aug 14;9(1):3258.
    pmc: PMC6092366pubmed: 30108219doi: 10.1038/s41467-018-05257-7google scholar: lookup
  44. Letunic I, Bork P. Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation.. Nucleic Acids Res 2021 Jul 2;49(W1):W293-W296.
    pmc: PMC8265157pubmed: 33885785doi: 10.1093/nar/gkab301google scholar: lookup
  45. Luo W, Sandy J, Trella K, Gorski D, Gao S, Li J, Brounts S, Galante J, Plaas A. Degenerative Suspensory Ligament Desmitis (DSLD) in Peruvian Paso Horses Is Characterized by Altered Expression of TGFβ Signaling Components in Adipose-Derived Stromal Fibroblasts.. PLoS One 2016;11(11):e0167069.
    pmc: PMC5130251pubmed: 27902739doi: 10.1371/journal.pone.0167069google scholar: lookup
  46. Lv L, Ye M, Duan R, Yuan K, Chen J, Liang W, Zhou Z, Zhang L. Downregulation of Pin1 in human atherosclerosis and its association with vascular smooth muscle cell senescence.. J Vasc Surg 2018 Sep;68(3):873-883.e5.
    pubmed: 28986099doi: 10.1016/j.jvs.2017.09.006google scholar: lookup
  47. Mak KM, Png CY, Lee DJ. Type V Collagen in Health, Disease, and Fibrosis.. Anat Rec (Hoboken) 2016 May;299(5):613-29.
    pubmed: 26910848doi: 10.1002/ar.23330google scholar: lookup
  48. Mendias CL, Gumucio JP, Lynch EB. Mechanical loading and TGF-β change the expression of multiple miRNAs in tendon fibroblasts.. J Appl Physiol (1985) 2012 Jul;113(1):56-62.
    pmc: PMC3404830pubmed: 22539168doi: 10.1152/japplphysiol.00301.2012google scholar: lookup
  49. Mero JL, Scarlett JM. Diagnostic criteria for degenerative suspensory ligament desmitis in Peruvian Paso horses. J Equine Vet Sci 2005;25(5):224–228.
  50. Mero JL, Pool R. Twenty cases of degenerative suspensory ligament desmitis in Peruvian Paso horses. AAEP Proc 2002;48:329–334.
  51. Metzger J, Distl O. Genetics of Equine Orthopedic Disease.. Vet Clin North Am Equine Pract 2020 Aug;36(2):289-301.
    pubmed: 32534855doi: 10.1016/j.cveq.2020.03.008google scholar: lookup
  52. Mi H, Muruganujan A, Casagrande JT, Thomas PD. Large-scale gene function analysis with the PANTHER classification system.. Nat Protoc 2013 Aug;8(8):1551-66.
    pmc: PMC6519453pubmed: 23868073doi: 10.1038/nprot.2013.092google scholar: lookup
  53. Mi H, Muruganujan A, Ebert D, Huang X, Thomas PD. PANTHER version 14: more genomes, a new PANTHER GO-slim and improvements in enrichment analysis tools.. Nucleic Acids Res 2019 Jan 8;47(D1):D419-D426.
    pmc: PMC6323939pubmed: 30407594doi: 10.1093/nar/gky1038google scholar: lookup
  54. Paradžik M, Humphries JD, Stojanović N, Nestić D, Majhen D, Dekanić A, Samaržija I, Sedda D, Weber I, Humphries MJ, Ambriović-Ristov A. KANK2 Links αVβ5 Focal Adhesions to Microtubules and Regulates Sensitivity to Microtubule Poisons and Cell Migration.. Front Cell Dev Biol 2020;8:125.
    pmc: PMC7063070pubmed: 32195252doi: 10.3389/fcell.2020.00125google scholar: lookup
  55. Patron J, Serra-Cayuela A, Han B, Li C, Wishart DS. Assessing the performance of genome-wide association studies for predicting disease risk.. PLoS One 2019;14(12):e0220215.
    pmc: PMC6894795pubmed: 31805043doi: 10.1371/journal.pone.0220215google scholar: lookup
  56. Pavlidis P, Jensen JD, Stephan W, Stamatakis A. A critical assessment of storytelling: gene ontology categories and the importance of validating genomic scans.. Mol Biol Evol 2012 Oct;29(10):3237-48.
    pubmed: 22617950doi: 10.1093/molbev/mss136google scholar: lookup
  57. Pérez P, de los Campos G. Genome-wide regression and prediction with the BGLR statistical package.. Genetics 2014 Oct;198(2):483-95.
    pmc: PMC4196607pubmed: 25009151doi: 10.1534/genetics.114.164442google scholar: lookup
  58. Petersen JL, Mickelson JR, Cothran EG, Andersson LS, Axelsson J, Bailey E, Bannasch D, Binns MM, Borges AS, Brama P, da Câmara Machado A, Distl O, Felicetti M, Fox-Clipsham L, Graves KT, Guérin G, Haase B, Hasegawa T, Hemmann K, Hill EW, Leeb T, Lindgren G, Lohi H, Lopes MS, McGivney BA, Mikko S, Orr N, Penedo MC, Piercy RJ, Raekallio M, Rieder S, Røed KH, Silvestrelli M, Swinburne J, Tozaki T, Vaudin M, M Wade C, McCue ME. Genetic diversity in the modern horse illustrated from genome-wide SNP data.. PLoS One 2013;8(1):e54997.
    pmc: PMC3559798pubmed: 23383025doi: 10.1371/journal.pone.0054997google scholar: lookup
  59. Plaas A, Sandy JD, Liu H, Diaz MA, Schenkman D, Magnus RP, Bolam-Bretl C, Kopesky PW, Wang VM, Galante JO. Biochemical identification and immunolocalizaton of aggrecan, ADAMTS5 and inter-alpha-trypsin-inhibitor in equine degenerative suspensory ligament desmitis.. J Orthop Res 2011 Jun;29(6):900-6.
    pubmed: 21246622doi: 10.1002/jor.21332google scholar: lookup
  60. Ponticos M, Papaioannou I, Xu S, Holmes AM, Khan K, Denton CP, Bou-Gharios G, Abraham DJ. Failed degradation of JunB contributes to overproduction of type I collagen and development of dermal fibrosis in patients with systemic sclerosis.. Arthritis Rheumatol 2015 Jan;67(1):243-53.
    pmc: PMC4312903pubmed: 25303440doi: 10.1002/art.38897google scholar: lookup
  61. nR Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2021.
  62. Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment.. Atherosclerosis 2012 Aug;223(2):262-8.
    pubmed: 22398274doi: 10.1016/j.atherosclerosis.2012.02.019google scholar: lookup
  63. Rees SG, Dent CM, Caterson B. Metabolism of proteoglycans in tendon.. Scand J Med Sci Sports 2009 Aug;19(4):470-8.
    pubmed: 19422635doi: 10.1111/j.1600-0838.2009.00938.xgoogle scholar: lookup
  64. Reynolds J, Weir BS, Cockerham CC. Estimation of the coancestry coefficient: basis for a short-term genetic distance.. Genetics 1983 Nov;105(3):767-79.
    pmc: PMC1202185pubmed: 17246175doi: 10.1093/genetics/105.3.767google scholar: lookup
  65. Sabatelli P, Gara SK, Grumati P, Urciuolo A, Gualandi F, Curci R, Squarzoni S, Zamparelli A, Martoni E, Merlini L, Paulsson M, Bonaldo P, Wagener R. Expression of the collagen VI α5 and α6 chains in normal human skin and in skin of patients with collagen VI-related myopathies.. J Invest Dermatol 2011 Jan;131(1):99-107.
    pubmed: 20882040doi: 10.1038/jid.2010.284google scholar: lookup
  66. Schaefer RJ, Schubert M, Bailey E, Bannasch DL, Barrey E, Bar-Gal GK, Brem G, Brooks SA, Distl O, Fries R, Finno CJ, Gerber V, Haase B, Jagannathan V, Kalbfleisch T, Leeb T, Lindgren G, Lopes MS, Mach N, da Câmara Machado A, MacLeod JN, McCoy A, Metzger J, Penedo C, Polani S, Rieder S, Tammen I, Tetens J, Thaller G, Verini-Supplizi A, Wade CM, Wallner B, Orlando L, Mickelson JR, McCue ME. Developing a 670k genotyping array to tag ~2M SNPs across 24 horse breeds.. BMC Genomics 2017 Jul 27;18(1):565.
    pmc: PMC5530493pubmed: 28750625doi: 10.1186/s12864-017-3943-8google scholar: lookup
  67. Scheet P, Stephens M. A fast and flexible statistical model for large-scale population genotype data: applications to inferring missing genotypes and haplotypic phase.. Am J Hum Genet 2006 Apr;78(4):629-44.
    pmc: PMC1424677pubmed: 16532393doi: 10.1086/502802google scholar: lookup
  68. Schenkman D, Armien A, Pool R, Williams JM, Schultz RD, Galante JO. Systemic proteoglycan deposition is not a characteristic of equine degenerative suspensory ligament desmitis (DSLD). J Equine Vet Sci 2009;29(10):748–752.
  69. Scholkopf B, Smola A, Muller KR. Kernal principal component analysis. International Conference on Artificial Neural Networks 1997. Berlin/Heidelberg: Springer. 583–588.
  70. Seetharaman S, Etienne-Manneville S. Cytoskeletal Crosstalk in Cell Migration.. Trends Cell Biol 2020 Sep;30(9):720-735.
    pubmed: 32674938doi: 10.1016/j.tcb.2020.06.004google scholar: lookup
  71. Shikh Alsook MK, Gabriel A, Salouci M, Piret J, Alzamel N, Moula N, Denoix JM, Antoine N, Baise E. Characterization of collagen fibrils after equine suspensory ligament injury: an ultrastructural and biochemical approach.. Vet J 2015 Apr;204(1):117-22.
    pubmed: 25795168doi: 10.1016/j.tvjl.2015.02.011google scholar: lookup
  72. Smith RKW, McIlwraith CW. "One Health" in tendinopathy research: Current concepts.. J Orthop Res 2021 Aug;39(8):1596-1602.
    pubmed: 33713481doi: 10.1002/jor.25035google scholar: lookup
  73. Smith SP, Phillips JB, Johnson ML, Abbot P, Capra JA, Rokas A. Genome-wide association analysis uncovers variants for reproductive variation across dog breeds and links to domestication.. Evol Med Public Health 2019;2019(1):93-103.
    pmc: PMC6592264pubmed: 31263560doi: 10.1093/emph/eoz015google scholar: lookup
  74. Sorensen DA, Andersen S, Gianola D, Korsgaard I. Bayesian inference in threshold models using Gibbs sampling. Genet Selec Evol 1995;27(3):229–249.
  75. Spencer AY, Lallier TE. Mechanical tension alters semaphorin expression in the periodontium.. J Periodontol 2009 Oct;80(10):1665-73.
    pubmed: 19792857doi: 10.1902/jop.2009.090212google scholar: lookup
  76. Strong DI. The use of a whole genome scan to find a genetic marker for degenerative suspensory ligament desmitis in the Peruvian Paso horse [master’s thesis]. University of Kentucky; 2005.
  77. Sved JA. Linkage disequilibrium and homozygosity of chromosome segments in finite populations.. Theor Popul Biol 1971 Jun;2(2):125-41.
    pubmed: 5170716doi: 10.1016/0040-5809(71)90011-6google scholar: lookup
  78. Tan GK, Pryce BA, Stabio A, Brigande JV, Wang C, Xia Z, Tufa SF, Keene DR, Schweitzer R. Tgfβ signaling is critical for maintenance of the tendon cell fate.. Elife 2020 Jan 21;9.
    pmc: PMC7025861pubmed: 31961320doi: 10.7554/elife.52695google scholar: lookup
  79. Tanaka J, Leeb T, Rushton J, Famula TR, Mack M, Jagannathan V, Flury C, Bachmann I, Eberth J, McDonnell SM, Penedo MCT, Bellone RR. Frameshift Variant in MFSD12 Explains the Mushroom Coat Color Dilution in Shetland Ponies.. Genes (Basel) 2019 Oct 19;10(10).
    pmc: PMC6827053pubmed: 31635058doi: 10.3390/genes10100826google scholar: lookup
  80. Thankam FG, Agrawal DK. Hypoxia-driven secretion of extracellular matrix proteins in the exosomes reflects the asymptomatic pathology of rotator cuff tendinopathies.. Can J Physiol Pharmacol 2021 Feb;99(2):224-230.
    pubmed: 32799660doi: 10.1139/cjpp-2020-0314google scholar: lookup
  81. Tilley BJ, Cook JL, Docking SI, Gaida JE. Is higher serum cholesterol associated with altered tendon structure or tendon pain? A systematic review.. Br J Sports Med 2015 Dec;49(23):1504-9.
    pmc: PMC4680137pubmed: 26474596doi: 10.1136/bjsports-2015-095100google scholar: lookup
  82. Van Inghelandt D, Reif JC, Dhillon BS, Flament P, Melchinger AE. Extent and genome-wide distribution of linkage disequilibrium in commercial maize germplasm.. Theor Appl Genet 2011 Jun;123(1):11-20.
    pubmed: 21404061doi: 10.1007/s00122-011-1562-3google scholar: lookup
  83. VanRaden PM. Efficient methods to compute genomic predictions.. J Dairy Sci 2008 Nov;91(11):4414-23.
    pubmed: 18946147doi: 10.3168/jds.2007-0980google scholar: lookup
  84. Verbrugge SAJ, Schönfelder M, Becker L, Yaghoob Nezhad F, Hrabě de Angelis M, Wackerhage H. Genes Whose Gain or Loss-Of-Function Increases Skeletal Muscle Mass in Mice: A Systematic Literature Review.. Front Physiol 2018;9:553.
    pmc: PMC5992403pubmed: 29910734doi: 10.3389/fphys.2018.00553google scholar: lookup
  85. Vitezica ZG, Varona L, Legarra A. On the additive and dominant variance and covariance of individuals within the genomic selection scope.. Genetics 2013 Dec;195(4):1223-30.
    pmc: PMC3832268pubmed: 24121775doi: 10.1534/genetics.113.155176google scholar: lookup
  86. Vos PG, Paulo MJ, Voorrips RE, Visser RG, van Eck HJ, van Eeuwijk FA. Evaluation of LD decay and various LD-decay estimators in simulated and SNP-array data of tetraploid potato.. Theor Appl Genet 2017 Jan;130(1):123-135.
    pmc: PMC5214954pubmed: 27699464doi: 10.1007/s00122-016-2798-8google scholar: lookup
  87. Wang T, Thien C, Wang C, Ni M, Gao J, Wang A, Jiang Q, Tuan RS, Zheng Q, Zheng MH. 3D uniaxial mechanical stimulation induces tenogenic differentiation of tendon-derived stem cells through a PI3K/AKT signaling pathway.. FASEB J 2018 Sep;32(9):4804-4814.
    pubmed: 29596022doi: 10.1096/fj.201701384rgoogle scholar: lookup
  88. Weir BS, Cockerham CC. ESTIMATING F-STATISTICS FOR THE ANALYSIS OF POPULATION STRUCTURE.. Evolution 1984 Nov;38(6):1358-1370.
    pubmed: 28563791doi: 10.1111/j.1558-5646.1984.tb05657.xgoogle scholar: lookup
  89. Weir BS, Hill WG. Effect of mating structure on variation in linkage disequilibrium.. Genetics 1980 Jun;95(2):477-88.
    pmc: PMC1214241pubmed: 7203003doi: 10.1093/genetics/95.2.477google scholar: lookup
  90. Winnicki K, Ochała-Kłos A, Rutowicz B, Pękala PA, Tomaszewski KA. Functional anatomy, histology and biomechanics of the human Achilles tendon - A comprehensive review.. Ann Anat 2020 May;229:151461.
    pubmed: 31978571doi: 10.1016/j.aanat.2020.151461google scholar: lookup
  91. Yeung CY, Gossan N, Lu Y, Hughes A, Hensman JJ, Bayer ML, Kjær M, Kadler KE, Meng QJ. Gremlin-2 is a BMP antagonist that is regulated by the circadian clock.. Sci Rep 2014 Jun 5;4:5183.
    pmc: PMC4046123pubmed: 24897937doi: 10.1038/srep05183google scholar: lookup
  92. Young JH. Degenerative suspensory ligament desmitis. Hoof Care and Lameness 1993;6–19.
  93. Young M, Moshood O, Zhang J, Sarbacher CA, Mueller POE, Halper J. Does BMP2 play a role in the pathogenesis of equine degenerative suspensory ligament desmitis?. BMC Res Notes 2018 Sep 18;11(1):672.
    pmc: PMC6145121pubmed: 30227887doi: 10.1186/s13104-018-3776-9google scholar: lookup
  94. Zhang M, Liu H, Cui Q, Han P, Yang S, Shi M, Zhang T, Zhang Z, Li Z. Tendon stem cell-derived exosomes regulate inflammation and promote the high-quality healing of injured tendon.. Stem Cell Res Ther 2020 Sep 17;11(1):402.
    pmc: PMC7499865pubmed: 32943109doi: 10.1186/s13287-020-01918-xgoogle scholar: lookup
  95. Zhu Y, Kakinuma N, Wang Y, Kiyama R. Kank proteins: a new family of ankyrin-repeat domain-containing proteins.. Biochim Biophys Acta 2008 Feb;1780(2):128-33.
    pubmed: 17996375doi: 10.1016/j.bbagen.2007.09.017google scholar: lookup

Citations

This article has been cited 6 times.
  1. Boado A, Pollard D, Lopez-Sanroman FJ, Dyson S. Orthopaedic Injuries in 272 Dressage Horses: A Retrospective Study. Animals (Basel) 2025 Oct 14;15(20).
    doi: 10.3390/ani15202972pubmed: 41153899google scholar: lookup
  2. Guest DJ, Birch HL, Thorpe CT. A review of the equine suspensory ligament: Injury prone yet understudied. Equine Vet J 2025 Sep;57(5):1167-1182.
    doi: 10.1111/evj.14447pubmed: 39604165google scholar: lookup
  3. Šimon M, Kaić A, Potočnik K. Unveiling Genetic Potential for Equine Meat Production: A Bioinformatics Approach. Animals (Basel) 2024 Aug 22;14(16).
    doi: 10.3390/ani14162441pubmed: 39199974google scholar: lookup
  4. Momen M, Brauer K, Patterson MM, Sample SJ, Binversie EE, Davis BW, Cothran EG, Rosa GJM, Brounts SH, Muir P. Genetic architecture and polygenic risk score prediction of degenerative suspensory ligament desmitis (DSLD) in the Peruvian Horse. Front Genet 2023;14:1201628.
    doi: 10.3389/fgene.2023.1201628pubmed: 37645058google scholar: lookup
  5. Dementieva N, Nikitkina E, Shcherbakov Y, Nikolaeva O, Mitrofanova O, Ryabova A, Atroshchenko M, Makhmutova O, Zaitsev A. The Genetic Diversity of Stallions of Different Breeds in Russia. Genes (Basel) 2023 Jul 24;14(7).
    doi: 10.3390/genes14071511pubmed: 37510415google scholar: lookup
  6. Roberts JH, Zhang J, David F, McLean A, Blumenshine K, Müller-Alander E, Halper J. Expression of genes with biomarker potential identified in skin from DSLD-affected horses increases with age. PLoS One 2023;18(7):e0287740.
    doi: 10.1371/journal.pone.0287740pubmed: 37450486google scholar: lookup
Subscribe to our newsletter
Join 99,824 horse owners like you who receive our email updates on horse health and nutrition.