Genetic and genomic analysis of early abortions in Israeli dairy cattle

Female infertility accounts for at least 50% of all human infertility cases. One of the causes contributing for female infertility is embryo loss after fertilization. Previous findings suggested that more than half of fertilizations results in embryo loss before pregnancy is detected. Dairy cattle may be a useful model for study of the genetic architecture of this trait. In advanced commercial populations, all breeding is by artificial insemination, and extensive records of the cows’ estrus, insemination and pregnancies are available. We proposed re-insemination between 49 and 100 days after the first insemination as an indicator trait for early abortion in dairy cattle, based on the mean estrus interval of 21 days. Israeli Holstein cows scored as early abortion were compare to cows recorded as pregnant from the first insemination. This trait was compare to conception rate from first insemination. Animal model variance components were estimated by REML, including parents and grandparents of cows with records. First parity heritability for conception rate was 3%. In the multi-trait analysis of parities 1-3 for abortion rate heritabilities ranged from 8.9% for first parity to 10.4% for second parity. The variance component for the service sire effect for abortion rate were less than half the variance component for conception rate. Thus genetic control of the two traits is clearly different. Genome wide association study were performed based on the genetic evaluations of ∼1200 sires with reliabilities >50%. The markers with the lowest probabilities for early abortion were also included among the markers with the lowest probabilities for conception rate, but not vice versa. The marker explaining the most variance for abortion rate is located within the ABCA9 gene, which is found within an ABC genes cluster. The ATP-binding cassette family is the major class of primary active transporters in the placenta.Author summaryApproximately 70% of human conceptions fail to achieve viability. Almost 50% of all pregnancies end in miscarriage before the clinical recognition of a missed period. Cattle are a useful model for human female reproductive processes, because of the similarities in the reproductive cycles, and the extensive documentation in commercial cattle populations, including estrus and insemination records. In addition to the expected benefits from cow fertility research for human biomedical applications, fertility is an economically important trait in dairy cattle with very low heritability. The mean estrous interval for cattle is 21 days. We therefore proposed re-insemination between 49 and 100 days after the first insemination as an indicator trait for early abortion. Israeli Holstein cows scored as having early abortion based on first insemination after parturition were compare to cows recorded as pregnant from the first insemination. Heritability for early abortion rate was three-fold the heritability for conception rate. In a genome wide association study based on 1200 dairy bulls genotyped for 41,000 markers, six markers were found with nominal probabilities of < 10-12 to reject the null hypothesis of no effect on early abortion rate. Early abortion rate may be a useful indicator trait for improvement of fertility in dairy cattle.