Porcine insulin receptor substrate 4 (IRS4) gene: cloning, polymorphism and association study.

Using PCR and inverse PCR techniques we obtained a 4,498 bp nucleotide sequence FN424076 encompassing the complete coding sequence of the porcine insulin receptor substrate 4 (IRS4) gene and its proximal promoter. The 1,269 amino acid porcine protein deduced from the nucleotide sequence shares 92% identity with the human IRS4 and possesses the same domains and the same number of tyrosine phosphorylation motifs as the human protein. We detected substitution FN424076:g.96C<G in the promoter region that segregates in Meishan and a synonymous substitution FN424076:g.1829T<C in the coding sequence with allele C present only in Meishan. Linkage mapping placed the IRS4 gene at position 82 cM on the current USDA-USMARC linkage map of porcine chromosome X. Association analyses were performed on 555 animals of 12th-15th generation of the Meishan × Large White cross and showed that both SNPs were highly significantly associated with backfat depth (P=0.0005) and that the SNP FN424076:g1829T<C was also associated with loin depth (P=0.017). The Meishan alleles increased back fat depth and decreased loin depth. IRS4 can be considered a positional candidate gene for at least some of the QTL located at the centromeric region of porcine chromosome X.