Identification of a nonsense mutation in APAF1 that is likely causal for a decrease in reproductive efficiency in Holstein dairy cattle

Authors: ADAMS, HEATHER - University Of Illinois; Sonstegard, Tad; Vanraden, Paul; Null, Daniel; Van Tassell, Curtis - Curt; LARKIN, DENIS - University Of Illinois; LEWIN, HARRIS - University Of Illinois

Submitted to: Journal of Dairy Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/23/2016
Publication Date: 8/1/2016
Citation: Adams, H.A., Sonstegard, T.S., Van Raden, P.M., Null, D.J., Van Tassell, C.P., Larkin, D.M., Lewin, H.A. 2016. Identification of a nonsense mutation in APAF1 that is likely causal for a decrease in reproductive efficiency in Holstein dairy cattle. Journal of Dairy Science. 99(8):6693-6701.

Interpretive Summary: A prominent Holstein sire from the 1960s was found to carry a lethal mutation (recessive mutation) that causes abortion in cattle. These abortions cause a significant economic loss to the dairy industry. A combination studies of whole genome sequencing and genotyping of this bull and his descendants was completed to identify the specific mutation in a gene affecting embryo development. The results of this study will be translated into a DNA marker test that will be available to producers to identify dairy cattle carrying this lethal mutation.

Technical Abstract: A haplotype on cattle chromosome 5 carrying a recessive lethal allele was found to originate in a Holstein-Friesian foundation sire. Resequencing led to the identification of a stop-gain mutation in exon 11 of APAF1, a gene known to cause embryonic lethality and neurodevelopmental abnormalities in knockout mice. This newly identified lethal mutation has been responsible for a substantial number of spontaneous abortions causing significant economic loss to the dairy industry.