{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T02:01:58Z","timestamp":1791684118708,"version":"4.3.4"},"reference-count":95,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["1R21AR07330-01"],"award-info":[{"award-number":["1R21AR07330-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,9,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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.<\/jats:p>","DOI":"10.1093\/g3journal\/jkac179","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T11:40:14Z","timestamp":1658490014000},"source":"Crossref","is-referenced-by-count":9,"title":["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"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2562-2741","authenticated-orcid":false,"given":"Mehdi","family":"Momen","sequence":"first","affiliation":[{"name":"Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison , Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8748-7912","authenticated-orcid":false,"given":"Sabrina H","family":"Brounts","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison , Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1991-0867","authenticated-orcid":false,"given":"Emily E","family":"Binversie","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison , Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8551-7460","authenticated-orcid":false,"given":"Susannah J","family":"Sample","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison , Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9172-6461","authenticated-orcid":false,"given":"Guilherme J M","family":"Rosa","sequence":"additional","affiliation":[{"name":"University of Wisconsin-Madison Department of Animal and Dairy Sciences, , Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6121-135X","authenticated-orcid":false,"given":"Brian W","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University , College Station, TX 77843, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0028-6005","authenticated-orcid":false,"given":"Peter","family":"Muir","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, School of 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