Genomic Differences Between Highly Fertile and Sub-Fertile Holstein Dairy Heifers



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Infertility in dairy cattle remains a major economic loss to dairy producers. Identifying dairy cattle with superior genetic potential for improved fertility would increase dairy farm profitability. Dairy heifers were classified into two groups based upon services per conception (SPC); those animals with a single SPC were determined to be highly fertile and animals with greater than or equal to 4 SPC were classified as sub-fertile. Whole genome association analysis was performed on 20 individual heifers from each group utilizing a 777K highly density (HD) single nucleotide polymorphism (SNP) chip. Genomic data were evaluated utilizing PLINK, a whole genome association analysis toolset, and 570,620 SNP were available for analysis with a total of 39 samples being analyzed. Forty-four SNP were determined to be associated with fertility classification (P <= 0.00001) and were located on Bos taurus chromosome (BTA) 2, 4, 9, 19, and 26. The SNP and ranges between SNP were analyzed using BLAST-Like Alignment Tool (BLAT); SNP were associated with 5 candidate genes for reproduction. The SNP on BTA 2 were located within the region coding for the non-imprinted Prader-Willi/Angelman syndrome 2 (NIPA2) gene, which is involved in gestational magnesium transport. Also on BTA 2, SNP were identified within the region encoding for cytoplasmic fragile X mental retardation 1 (FMR1) interaction protein 1 (CYFIP1). The CYFIP1 gene is involved with the functionality of FMR1 and has been linked to premature ovarian failure in humans. Additionally, 3 SNP on BTA 9 were located near monofunctional C1-tetrahydrofolate synthase (MTHFD1L), which has been linked to neural tube defects during gestation in humans A difference in allele frequency was observed between the two groups for SNP located on BTA19 in proximity to two genes, zinc finger 18 (ZNF18) and mitogen activated protein kinase 4 (MAP2K4). The ZNF18 motif and MAP2K4 were found to be involved in heart development of the early embryo and associated with toll-like receptors (TLR) involved in gonadotropin releasing hormone (GnRH) signaling, respectively. The involvement of one or all of these genes may further explain reduced fertility in dairy cattle.