Polymorphisms in the selectin gene cluster are associated with fertility and survival time in a population of Holstein Friesian cows

Abstract

Selectins are adhesion molecules, which mediate attachment between leucocytes and endothelium. They aid extravasation of leucocytes from blood into inflamed tissue during the mammary gland’s response to infection. Selectins are also involved in attachment of the conceptus to the endometrium and subsequent placental development. Poor fertility and udder health are major causes for culling dairy cows. The three identified bovine selectin genes SELP, SELL and SELE are located in a gene cluster. SELP is the most polymorphic of these genes. Several SNP in SELP and SELE are associated with human vascular disease, while SELP SNP rs6127 has been associated with recurrent pregnancy loss in women. This study describes the results of a gene association study for SNP in SELP (n = 5), SELL (n = 2) and SELE (n = 1) with fertility, milk production and longevity traits in a population of 337 Holstein Friesian dairy cows. Blood samples for PCR-RFLP were collected at 6 months of age and animals were monitored until either culling or 2,340 days from birth. Three SNP in SELPEx4-6 formed a haplotype block containing a Glu/Ala substitution at rs42312260. This region was associated with poor fertility and reduced survival times. SELPEx8 (rs378218397) coded for a Val475Met variant locus in the linking region between consensus repeats 4 and 5, which may influence glycosylation. The synonymous SNP rs110045112 in SELEEx14 deviated from Hardy Weinberg equilibrium. For both this SNP and rs378218397 there were too few AA homozygotes present in the population and AG heterozygotes had significantly worse fertility than GG homozygotes. Small changes in milk production associated with some SNP could not account for the reduced fertility and only SELPEx6 showed any association with somatic cell count. These results suggest that polymorphisms in SELP and SELE are associated with the likelihood of successful pregnancy, potentially through compromised implantation and placental development.

Adhesion molecules in gamete transport, fertilization, early embryonic development, and implantation—role in establishing a pregnancy in cattle: A review

“…Whole‐genome association studies have an important application in identifying SNPs for embryo survival and pregnancy in cattle. For example, SNPs in the l ‐selectin gene cluster were associated with fertility and longevity in Holstein Friesian cows (X. Chen et al, 2017). In a recent study in female Brahman and Nellore cattle (de Melo, Fortes, Hayes, de Albuquerque, & Carvalheiro, 2019), SNPs associated with fertility were linked with blastocyst development (genes GCGN , ATF6B ; Gad et al, 2011), embryonic development (genes NF1B , NAPA , ZPR1 , TAF8 , HEX1M1 , HEX1M2 ; Mamo et al, 2011; Al Naib, Mamo, & Lonergan, 2012), uterine function (genes C11H2orf49 , CCND3 ; Hayashi et al, 2017), and general cell proliferation and morphogenesis (gene CHSY1 ; Becker‐Santos, Lonergan, Gronostajski, & Lam, 2017).…”

“…For example, SNPs in the L-selectin gene cluster were associated with fertility and longevity in Holstein Friesian cows (X. Chen et al, 2017). In a recent study in female Becker-Santos, Lonergan, Gronostajski, & Lam, 2017).…”

Association between Single Nucleotide Polymorphism in RelA with Somatic Cell Count and Longevity Supports Importance of NF-κB Signalling in Cattle Health

“…Data on SCC from monthly milk analysis records were averaged over each lactation. Milk phenotype data for lactation 1 only and "all lactations" were calculated as residuals (L1) or cow effect (LAll) after fitting a mixed model to all herd data [25]. A trait to represent mastitis status was derived from the SCC data after Yoshida et al [26].…”

“…DNA from blood samples was extracted using a Flexi- each of 10 British Holstein cows were used to construct the DNA pool. PCR was performed using a Qiagen Multiplex PCR kit as described previously [25]. Sequence files were assessed using the Chromas Pro software package (release 2.33;…”

“…The appropriate enzyme was selected using the WatCut online tool (http://watcut.uwaterloo.ca/template.php?act=snp_new). PCR was then performed using a Qiagen multiplex PCR kit as described previously [25]. Thereafter, 10 μl PCR products were digested with 2 U restriction enzyme BsrBI (New England Biolabs Inc, Hitchin, Herts, UK) in a 20 μl reaction volume at 37˚C.…”