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The adverse effects of inbreeding on phenotypic performance are well established, but the genetic variants contributing to inbreeding depression remain largely unknown. This study aimed to analyse the impacts of inbreeding on stature (measured as height at the sacral bone) in a cohort of 15,306 Brown Swiss (BS) cows that have imputed genotypes at 20 million sequence variants and stature measurements as height at the sacral bone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The average genomic inbreeding coefficient of the 15,306 BS cows estimated from runs of homozygosity (ROH) was 0.369 (\u00b1\u20090.022). We found a loss in stature, with height at the sacral bone decreasing by 0.076\u00a0cm per 1% increase in inbreeding (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.94e\u221209). Contributions to inbreeding depression were significant for long (&gt;\u20092\u00a0Mb), medium (&gt;\u20090.1\u2013\u2264\u20092\u00a0Mb), and short (\u2265\u200950\u00a0kb\u2013\u2264\u20090.1\u00a0Mb) ROH (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.29e\u221212,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20093.20e\u221204 and\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20091.77e\u221206, respectively), suggesting that both ancient and recent inbreeding have negative effects on stature. Non-additive association testing identified a novel recessive quantitative trait locus (QTL) for stature on chromosome 25, with the most significantly associated SNP (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20092.35e\u221221) residing at 14,535,327\u00a0bp. Cows homozygous for the alternate allele of the top-associated SNP were 2\u00a0cm shorter than heterozygous and reference allele homozygotes. Fine mapping of the QTL identified a splice donor variant (rs447836030 at 25:14,515,474) of the gene\n                      <jats:italic>ABCC6<\/jats:italic>\n                      encoding ATP-binding cassette subfamily C member 6 which causes exon skipping as both a positional and functional candidate causal variant\n                      <jats:italic>.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our study reveals evidence for inbreeding depression on stature in a large cohort of BS cattle. We also uncover a recessive QTL that decreases stature through non-additive association testing. This QTL harbors a high-impact variant affecting a splice donor site of\n                      <jats:italic>ABCC6<\/jats:italic>\n                      which leads to exon skipping, thereby possibly contributing to inbreeding depression. Accumulating non-lethal deleterious alleles in ROH may reduce the overall fitness of the BS cattle population.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12711-026-01062-9","type":"journal-article","created":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T19:35:47Z","timestamp":1782675347000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genomic partitioning and functional dissection of inbreeding depression for stature in Brown Swiss cattle"],"prefix":"10.1186","volume":"58","author":[{"given":"Qiongyu","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Deuber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franz R.","family":"Seefried","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hubert","family":"Pausch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2799-3896","authenticated-orcid":false,"given":"Naveen Kumar","family":"Kadri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"1062_CR1","unstructured":"Falconer DS, Mackay TFC. 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