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.
Highlights
Failure to conceive in a timely fashion is the major reason for culling dairy cows [1, 2]
SELP was found to have the highest level of polymorphism as nine of the 13 SNPs were located in SELP exons, including three missense mutations
This is highly likely to be driven by host-pathogen co-evolution, such as to malaria parasites, as SELP is involved in the adherence of Plasmodium falciparum-infected erythrocytes to vascular-endothelial cells [57]
Summary
Failure to conceive in a timely fashion is the major reason for culling dairy cows [1, 2]. And late embryo mortality and abortion are estimated to occur in around 40%, 20% and 5% respectively of all pregnancies in high yielding dairy cows [3]. The causes of these losses are diverse and include disease and metabolic imbalance [4]. Similar to the bovine situation, it has been estimated that 70% of conceptions in the human population are lost between fertilization and a live birth due to implantation failure, early pregnancy loss or abortion [7]. Gross chromosomal abnormalities appear relatively more common [7, 8], whereas in cows advances in genome sequencing technologies have revealed a large number of loss-of-function variants, which are lethal during embryonic development [9]
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