The IGF1 pathway genes and their association with age of puberty in cattle.

Insulin-like growth factor I (somatomedin C) (IGF1) influences gonadotrophin-releasing hormone (GnRH) neurons during puberty, and GnRH release guides pubertal development. Therefore, genes of the IGF1 pathway are biological candidates for the identification of single-nucleotide polymorphisms (SNPs) affecting age of puberty. In a genome-wide association study, genotyped heifers were Tropical Composite (TCOMP, n = 866) or Brahman (BRAH, n = 843), with observation of age at first corpus luteum defining puberty. We examined SNPs in or near genes of the IGF1 pathway and report seven genes associated with age at puberty in cattle: IGF1R, IGFBP2, IGFBP4, PERK (HUGO symbol EIF2AK3), PIK3R1, GSK3B and IRS1. SNPs in the IGF1 receptor (IGF1R) showed the most promising associations: two SNPs were associated with puberty in TCOMP (P < 0.05) and one in BRAH (P = 0.00009). This last SNP explained 2% of the genetic variation (R(2) = 2.04%) for age of puberty in BRAH. Hence, IGF1R was examined further. Additional SNPs were genotyped, and haplotypes were analysed. To test more SNPs in this gene, four new SNPs from dbSNP were selected and genotyped. Single SNP and haploytpe analysis revealed associations with age of puberty in both breeds. There were two haplotypes of 12 IGF1R SNPs associated with puberty in BRAH (P < 0.05) and one in TCOMP (P < 0.05). One haplotype of two SNPs was associated (P < 0.01) with puberty in BRAH, but not in TCOMP. In conclusion, the IGF1 pathway appeared more relevant for age of puberty in Brahman cattle, and IGF1R showed higher significance when compared with other genes from the pathway.