{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T22:18:18Z","timestamp":1788387498902,"version":"build-2803163510"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Anterior cruciate ligament (ACL) rupture is a common orthopaedic disease in dogs, with varying prevalence and genetic susceptibility across different breeds. Here we investigate the association between genomic structural variation (SV) and ACL rupture risk in the Labrador Retriever and Rottweiler breeds.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used 1,058 Labrador Retrievers (464 cases, 594 controls) and 108 Rottweilers (83 cases, 25 controls). Using breed\u2010specific de novo genome assemblies, we first characterized SV between Labrador Retriever and Rottweiler genomes to provide genomic context for breed-level differences. We then quantified runs of homozygosity (ROH) and evaluated the association between homozygosity measures (nROH, AVGROH, and F\n                      <jats:sub>ROH<\/jats:sub>\n                      ) and ACL rupture risk using breed\u2010specific and combined\u2010breed logistic regression models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The association between homozygosity parameters and ACL rupture in the Labrador Retriever was not significant (\n                      <jats:italic>P<\/jats:italic>\n                      &amp;gt; 0.05 for all models). In contrast, inbreeding coefficient (F\n                      <jats:sub>ROH<\/jats:sub>\n                      ) was significantly associated with increased ACL rupture risk (OR = 2.011, 95% CI:1.120\u20103.98,\n                      <jats:italic>P<\/jats:italic>\n                      \u2010value = 0.026) in the Rottweiler when sex and interaction effects were included in the model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings suggest a potential association between inbreeding and ACL rupture risk in Rottweilers. In addition, joint analysis of Labrador Retriever and Rottweiler data revealed multicollinearity between breed and homozygosity content, which highlights the heterogeneity of genetic risk factors across breeds. Our findings suggest that breed\u2010specific genetic models are crucial for understanding the genetic contribution to ACL rupture and for developing accurate genetic risk prediction tools. Given the relatively small and imbalanced Rottweiler dataset, independent validation in larger populations is warranted to further explore the potential breed\u2010specific genetic loci contributing to ACL rupture in the Rottweiler.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1875383","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T22:10:37Z","timestamp":1788387037000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Influence of homozygosity on genomic structural variation analyses for predicting ACL rupture risk in the Labrador Retriever and Rottweiler"],"prefix":"10.3389","volume":"17","author":[{"given":"Mehdi","family":"Momen","sequence":"first","affiliation":[{"name":"Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison","place":["Madison, WI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faris Hazim Mohamed","family":"Zaimir","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison","place":["Madison, WI, United States"]},{"name":"Department of Computer Sciences, School of Computer, Data & Information Sciences, University of Wisconsin-Madison","place":["Madison, WI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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","place":["College Station, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susannah J.","family":"Sample","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison","place":["Madison, WI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Muir","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison","place":["Madison, WI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e0173810","DOI":"10.1371\/journal.pone.0173810","article-title":"Genome-wide association analysis in dogs implicates 99 loci as risk variants for anterior cruciate ligament rupture","volume":"12","author":"Baker","year":"2017","journal-title":"PLoS One"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.1534\/g3.120.401244","article-title":"Bayesian and machine learning models for genomic prediction of anterior cruciate ligament rupture in the canine model","volume":"10","author":"Baker","year":"2020","journal-title":"G3 (Bethesda)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"593515","DOI":"10.3389\/fgene.2021.593515","article-title":"Biologically enhanced genome-wide association study provides further evidence for candidate loci and discovers novel loci that influence risk of anterior cruciate ligament rupture in a dog model","volume":"12","author":"Baker","year":"2021","journal-title":"Front. 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