Sammanfattning

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 x 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 x 10(-22), 2.06 x 10(-22), 7.01 x 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 x 10(-10) and 7.4 x 10(-11), respectively). Finally, we identified and confirmed the breakpoint of a similar to 525 KB deletion on Chr23: 12,291,761-12,817,087 (overlapping BTBD9, GLO1 and DNAH8), causing stillbirth in Nordic Red Cattle.

Nyckelord

dairy cattle; structural variants; whole genome sequence; population genetics; loss-of-function

Publicerad i

DNA Research
2018, Volym: 25, nummer: 1, sidor: 49-59
Utgivare: OXFORD UNIV PRESS

SLU författare

• de Koning, Dirk-Jan

  • Institutionen för husdjurens biovetenskaper, Sveriges lantbruksuniversitet
    

UKÄ forskningsämne

Genetik och förädling


Publikationens identifierare

DOI: https://doi.org/10.1093/dnares/dsx037

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/94265