A Deletion in the Bovine FANCI Gene Compromises Fertility by Causing Fetal Death and Brachyspina

Fertility is one of the most important traits in dairy cattle, and has been steadily declining over the last decades.  We herein use state-of-the-art genomic tools, including high-throughput SNP genotyping and next-generation sequencing, to identify a deletion in the FANCI gene causing the brachyspina syndrome (BS), a rare genetic defect in Holstein dairy cattle.  We demonstrate that despite the very low incidence of BS, carrier frequency is as high as 7.4% in the Holstein breed.  We demonstrate that this apparent discrepancy is due to the fact that a large proportion of affected calves die during pregnancy.  The major economic impact of BS is thus through its effect on fertility.  We postulate that several other embryonic lethals may segregate in livestock and significantly compromise fertility.  We propose a genotype-driven screening strategy to detect the corresponding deleterious mutations.