A genome-wide association study reveals fetal genetic factor for gestation length on chromosome 21 in Japanese Black cattle.

Gestation length (GL) in cattle is associated with neonatal health and the subsequent reproductive performance of dams. We performed a genome-wide association study (GWAS) using 25,144 single nucleotide polymorphisms (SNPs) in 4373 animals to detect genetic variants associated with GL as a fetal trait in Japanese Black cattle in Gifu Prefecture. We identified four significant SNPs on chromosome 21 in moderate linkage disequilibrium (LD). The minor allele of the most significant SNP has the effect on -2.47 days GL with a 0.019 allele frequency. Of the 4373 animals, 140 heterozygotes and one homozygote with the minor allele were traced back to a heterozygous sire. The 7.2 Mb LD region harbors three genes: gamma-aminobutyric acid type A receptor subunit beta3 (GABRB3), arrestin domain containing 4 (ARRDC4), and nuclear receptor subfamily 2 group F member 2 (NR2F2, also known as COUP-TFII). RNA expression analysis and its functions suggest that GABRB3, ARRDC4, and NR2F2 (COUP-TFII) are involved in glucose production via the hypothalamic-pituitary-adrenal axis during the fetal stress response at gestation period termination. These results suggest that an increase in the allele frequency of the associated SNPs has an impact on genetic improvement by shortening the GL in the population.