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Genome-wide mapping of large deletions and their population-genetic properties in dairy cattle

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  • Md Mesbah-Uddin, UMR 1313 GABI, INRA, AgroParis Tech, Université Paris-Saclay, Jouy-en-Josas
  • ,
  • Bernt Guldbrandtsen
  • ,
  • Terhi Iso-Touru, Natural Resources Institute Finland, Green Technology, FI-31600 Jokioinen, Finland.
  • ,
  • Johanna Vilkki, Natural Resources Institute Finland, Green Technology, FI-31600 Jokioinen, Finland.
  • ,
  • Dirk-Jan De Koning, Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, SE-750 07 Uppsala, Sweden.
  • ,
  • Didier Boichard, UMR 1313 GABI, INRA, AgroParis Tech, Université Paris-Saclay, Jouy-en-Josas, France
  • Mogens Sandø Lund
  • Goutam Sahana

Large genomic deletions are potential candidate for loss-of-function, which could be lethal as homozygote. Analysing whole genome data of 175 cattle, we report 8,480 large deletions (199 bp-773 KB) with an overall false discovery rate of 8.8%; 82% of which are novel compared with deletions in the dbVar database. Breakpoint sequence analyses revealed that majority (24 of 29 tested) of the deletions contain microhomology/homology at breakpoint, and therefore, most likely generated by microhomology-mediated end joining. We observed higher differentiation among breeds for deletions in some genic-regions, such as ABCA12, TTC1, VWA3B, TSHR, DST/BPAG1, and CD1D. The genes overlapping deletions are on average evolutionarily less conserved compared with known mouse lethal genes (P-value = 2.3 × 10-6). We report 167 natural gene knockouts in cattle that are apparently nonessential as live homozygote individuals are observed. These genes are functionally enriched for immunoglobulin domains, olfactory receptors, and MHC classes (FDR = 2.06 × 10-22, 2.06 × 10-22, 7.01 × 10-6, respectively). We also demonstrate that deletions are enriched for health and fertility related quantitative trait loci (2-and 1.5-fold enrichment, Fisher's P-value = 8.91 × 10-10 and 7.4 × 10-11, respectively). Finally, we identified and confirmed the breakpoint of a ∼525 KB deletion on Chr23:12,291,761-12,817,087 (overlapping BTBD9, GLO1 and DNAH8), causing stillbirth in Nordic Red Cattle.

Original languageEnglish
JournalD N A Research
Pages (from-to)49-59
Number of pages11
Publication statusPublished - 1 Feb 2018

    Research areas

  • ASSOCIATION, BEEF-CATTLE, BREEDS, COPY NUMBER VARIATION, GROWTH, HOLSTEIN CATTLE, PROTEIN, STRUCTURAL VARIATION, TOOL, TRAITS, dairy cattle, loss-of-function, population genetics, structural variants, whole genome sequence

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