Submitted to: Journal of Dairy Science
Publication Type: Abstract Only
Publication Acceptance Date: 2/27/2017
Publication Date: 6/24/2017
Citation: Null, D.J., Hutchison, J.L., Bickhart, D.M., Van Raden, P.M., Cole, J.B. 2017. Discovery of a haplotype affecting fertility in Ayrshire dairy dattle and identification of a putative causal variant. Journal of Dairy Science. 100(Suppl. 2):199(abstr. 205).
Technical Abstract: Initial genomic test results for US Ayrshire dairy cattle became available in January of 2013. Several haplotypes that showed a deficiency of homozygotes were investigated to determine if they had an effect on fertility. A haplotype on chromosome 17 was determined to affect fertility, indicating that affected embryos died early in development, and was designated as Ayrshire haplotype 1 (AH1). Subsequent research identified the causal variant in the ubiquitin protein ligase E3B gene. Routine Ayrshire genomic evaluations were first released in April of 2013, and a new haplotype reached the threshold (7 expected homozygotes and none observed) by October 2013. Sire concenception rate was 6.1% lower for matings of carrier sires to cows with carrier maternal grandsires. However, with only 247 such matings the effect was not significant. The number of expected homozygotes has continued to increase since that time, and as of December 2016 the haplotype had reached 23.5 expected homozygotes. The oldest genotyped carrier is OAK-RIDGE FLASHY KELLOGG (AYUSA000000125168), born in 1961. The majority of carriers trace back to Kellogg, but a substantial number of Canadian carriers only trace back as far as WOODLAND VIEW PARDNER ET (AYCAN000000811799), born in 1994. These two bulls share a common ancestor in OAK-RIDGE LIGHTNING (AYUSA000000120135), born in 1958, but his carried status is unknown because he is not genotyped. This haplotype has been designated Ayrshire haplotype 2 (AH2), and the carrier frequency is currently 18.9% for AH2, and has increased from 6% in animals born in 1990 to 21.7% for animals born since 2008. Whole-genome sequence data ranging from 9 x to 13 x read-depth for 8 Ayrshire bulls collected during a previous project, including 3 carriers and 5 non-carriers, was examined to see if a candidate mutation could be identified. The analysis was conducted using a short-read sequence data analysis pipeline including BWA (version 0.7.10) and Samtools (version 1.3). Filters that removed likely false positive variants and variants with low (small) predicted functional effects were applied to the data after annotation using SNPeFF (version 4.3) annotation. After filtering variants in the suspect region, a splice acceptor variant at 51,267,548 bp in the RNA Polymerase 2 associated protein (RPAP2) gene was identified as the leading candidate mutation in the haplotype. The protein encoded by RPAP2 is an essential component of the RNA polymerase 2 holoenzyme necessary for transcription of snRNA species. Experiments with mouse knock-outs also found a deficiency of homozygotes, and concluded that RPAP2 is necessary for embryonic development. These findings, in combination with the suggestive effect on sire conception rate, provide strong indirect evidence for the existence a new, embryonic lethal recessive in Ayrshire dairy cattle. Given its current (and increasing) frequency, AH2 carrier status should be reported to the industry, and its effects on fertility should be confirmed.