Validation of 46 loci associated with female fertility traits in cattle

Abstract

Background: Subfertility is one challenge facing the dairy industry as the average Holstein heifer conception rate (HCR), the proportion of heifers that conceive and maintain a pregnancy per breeding, is estimated at 55-60%. Of the loci associated with HCR, few have been validated in an independent cattle population, limiting their usefulness for selection or furthering our understanding of the mechanisms involved in successful pregnancy. Therefore, the objectives here were to identify loci associated with HCR: 1) to the first artificial insemination (AI) service (HCR1), 2) to repeated AI services required for a heifer to conceive (TBRD) and 3) to validate loci previously associated with fertility. Breeding and health records from 3359 Holstein heifers were obtained after heifers were bred by AI at observed estrus, with pregnancy determined at day 35 via palpation. Heifer DNA was genotyped using the Illumina BovineHD BeadChip, and genome-wide association analyses (GWAA) were performed with additive, dominant and recessive models using the Efficient Mixed Model Association eXpedited (EMMAX) method with a relationship matrix for two phenotypes. The HCR1 GWAA compared heifers that were pregnant after the first AI service (n = 497) to heifers that were open following the first AI service (n = 405), which included those that never conceived. The TBRD GWAA compared only those heifers which did conceive, across variable numbers of AI service (n = 712). Comparison of loci previously associated with fertility, HCR1 or TBRD were considered the same locus for validation when in linkage disequilibrium (D' > 0.7). Results: The HCR1 GWAA identified 116, 187 and 28 loci associated (P < 5 × 10 − 8) in additive, dominant and recessive models, respectively. The TBRD GWAA identified 235, 362, and 69 QTL associated (P < 5 × 10 − 8) with additive, dominant and recessive models, respectively. Loci previously associated with fertility were in linkage disequilibrium with 22 loci shared with HCR1 and TBRD, 5 HCR1 and 19 TBRD loci. Conclusions: Loci associated with HCR1 and TBRD that have been identified and validated can be used to improve HCR through genomic selection, and to better understand possible mechanisms associated with subfertility.

Identification of Loci and Pathways Associated with Heifer Conception Rate in U.S. Holsteins

“…Two groups of heifers were combined for this study after receiving approval from Washington State University’s Institutional Animal Use and Care Committee (#4295). The first group consisted of 3060 heifers that were raised together at a heifer raising facility in Idaho, USA, as described by Kiser et al 2019 (a) [ 9 ]. The second group consisted of 1071 two-year-old cows whose conception data was obtained as yearling heifers [ 10 ].…”

Genomic Analysis of Spontaneous Abortion in Holstein Heifers and Primiparous Cows

“…Consequently, in Holstein cattle, conception rate has improved approximately 6 percentage points in heifers and 11 percentage points in cows since its inclusion in selection indexes in 2010 [13,14]. Although more recent studies have focused on the more prevalent early embryonic loss [15][16][17][18], additional research investigating fetal loss is needed, as very little is known about the genomic structure and physiological mechanisms responsible. In order to improve upon that knowledge, it is necessary to understand which genomic regions, genes, gene-sets, and pathways are associated with SA.…”

Direct Phenotyping and Principal Component Analysis of Type Traits Implicate Novel QTL in Bovine Mastitis through Genome-Wide Association

“…A case–control GWA for extremes in this phenotype (loose attachment, representing most at risk; tight attachment, representing least at risk) implicated a number of genes related to both immune function and cell proliferation near associated markers at 2:126354670-126359098 ( Figure 2 ). This QTL has been previously mapped for multiple types of milk acid content, milk fat yield, as well as conception rate [ 28 , 29 , 30 ]. Among candidate genes in this region is the immunomodulator Wiskott–Aldrich Syndrome Protein Family 2 ( WASF2 ), a cytoplasmic protein implicated in cell migration, phagocytosis, and immune synapse formation [ 31 ].…”