Gene function & annotation

Population-wide screening of large Copy Number Variations in 150,000 Holstein cattle reveals novel genetic defects

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Abstract

Copy Number Variations (CNVs) are deletions or duplications that can markedly affect gene dosage, and consequently, animal fitness traits. We developed a genome-wide screening pipeline to detect large CNVs ( >500 kb) from routine genotyping of animals on Illumina EuroGenomics MD arrays (50K+, v3 to v6). Our pipeline was applied to 150,053 Holstein cattle born between 2023 and 2025 across Europe, representing the largest population screened for CNVs using routine genotyping data. The detection algorithm was based on Log R Ratio deviations (increased or decreased fluorescence) and B Allele Frequency (local loss of heterozygosity or gain of a third copy) interpretation. It was combined with Mendelian inconsistency checks when parental genotypes were available, to remove recurrent false positives. Across all genotypes, 1,128 (0.82%) showed major copy number abnormalities, including 108 whole-chromosome events (mostly X monosomy/trisomy or BTA27 trisomy), 826 deletions, and 193 duplications. Eight CNVs were recurrently observed, including three duplications (ranging from 546 kb to 6,2 Mb) and five deletions (505 kb to 4.9 Mb). Three of these deletions traced back to recently used insemination bulls, born after 2020. The largest event (BTA2:68.8 to 73.7 Mb) corresponded to a reciprocal translocation breakpoint. Another deletion on BTA9 (24.0-26.8 Mb) was segregating in a family of active bulls. Among 1,091 offspring (of which 92 were tested for fluorescence), carriers of this deletion showed as consequences significantly reduced survival (74.4% vs. 88.2% alive at 15 months, p = 8.5 à— 10-10) and decreased birth weight (38.8 kg vs. 30.6, p = 3.4 à— 10-63). A 505-kb deletion (BTA2:103.8-104.3 Mb) was also repeatedly identified in the progeny of a young bull and was probably involved in a reduced survival rate of calves. Leveraging such genotyping by-product dataset enabled the identification of deleterious CNVs, and the estimation of their prevalence across a large, population-wide cohort. This approach provides a cost-effective means to quantify the risk associated with large CNVs. It supports a proactive and smooth management of such defects in elite candidates, as an immediately available tool, enhancing the overall efficacy of breeding programs by integrating early detection of structural variants. Anticipating the emergence of such variants will help sustain long-term genetic progress and population health in cattle.

Keywords: 2026

How to Cite:

Jourdain, J., Piedfer, L., Schmidtmann, C. & Meier, S., (2026) “Population-wide screening of large Copy Number Variations in 150,000 Holstein cattle reveals novel genetic defects”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2286359. doi: https://doi.org/10.31274/wcgalp.23954

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