Genetic and genomic analysis of early abortions in Israeli dairy cattle

Abstract

20Female infertility accounts for at least 50% of all human infertility cases. One of the causes 21 contributing for female infertility is embryo loss after fertilization. Previous findings suggested 22 that more than half of fertilizations results in embryo loss before pregnancy is detected. Dairy 23 cattle may be a useful model for study of the genetic architecture of this trait. In advanced 24 commercial populations, all breeding is by artificial insemination, and extensive records of the 25 cows' estrus, insemination and pregnancies are available. We proposed re-insemination between 26 49 and 100 days after the first insemination as an indicator trait for early abortion in dairy cattle, 27 based on the mean estrus interval of 21 days. Israeli Holstein cows scored as early abortion were 28 compare to cows recorded as pregnant from the first insemination. This trait was compare to 29 conception rate from first insemination. Animal model variance components were estimated by 30 REML, including parents and grandparents of cows with records. First parity heritability for 31 conception rate was 3%. In the multi-trait analysis of parities 1-3 for abortion rate heritabilities 32 ranged from 8.9% for first parity to 10.4% for second parity. The variance component for the 33 service sire effect for abortion rate were less than half the variance component for conception 34 rate. Thus genetic control of the two traits is clearly different. Genome wide association study 35 were performed based on the genetic evaluations of ~1200 sires with reliabilities >50%. The 36 markers with the lowest probabilities for early abortion were also included among the markers 37 with the lowest probabilities for conception rate, but not vice versa. The marker explaining the 38 most variance for abortion rate is located within the ABCA9 gene, which is found within an 39 ABC genes cluster. The ATP-binding cassette family is the major class of primary active 40 transporters in the placenta. 3 41 42 Author summary 43 44 Approximately 70% of human conceptions fail to achieve viability. Almost 50% of all 45 pregnancies end in miscarriage before the clinical recognition of a missed period. Cattle are a 46 useful model for human female reproductive processes, because of the similarities in the 47 reproductive cycles, and the extensive documentation in commercial cattle populations, 48including estrus and insemination records. In addition to the expected benefits from cow fertility 49 research for human biomedical applications, fertility is an economically important trait in dairy 50 cattle with very low heritability. The mean estrous interval for cattle is 21 days. We therefore 51 proposed re-insemination between 49 and 100 days after the first insemination as an indicator 52 trait for early abortion. Israeli Holstein cows scored as having early abortion based on first 53 insemination after parturition were compare to cows recorded as pregnant from the first 54 insemination. Heritability for early abortion rate was three-fold the herit...