分子与遗传医学

Bovine-Specific Nucleotide Polymorphisms and mRNA Expression of the Growth Hormone Secretagogue Receptor 1a (GHSR1a) Gene and its Genetic Association with Growth and Carcass Traits

Abstract

Masanori Komatsu, Yoichi Sato, Yuki Fujimori, Tomohito Itoh, Masahiro Satoh, Motohide Nishio, Osamu Sasaki, Hideaki Takahashi and Aduli EO Malau-Aduli

The growth hormone secretagogue receptor 1a (GHSR1a) is involved in many important functions including growth hormone (GH) secretion and appetite regulation and other important functions. We reveal herein, the unravelling of bovine-specific 5’untranslated region (5’UTR) microsatellite polymorphisms, a 3bp-indel in exon 1 (DelR242) and two different kinds of transcripts of the GHSR1a gene (spliced, without a microsatellite with in the 5’UTR (GHSR1a); and non-spliced, with the microsatellite (GHSR1b)). A number of 17 alleles ((TG)10~33 ) in the 5’UTR microsatellite was found in 11 cattle breeds. Furthermore, we found the DelR242 (3R) allele, a truncated 3- arginine residue (3R) (major type: 4 arginine residues (4R)) within the intracellular loop 3 of GHSR1a protein in Japanese Shorthorn with a high frequency of 0.43 compared to the low frequency of 0.00~0.09 in other cattle breeds. We carried out a genetic association study between the 5’UTR microsatellite and growth and carcass traits in 1,285 steers. Statistical analysis revealed that the 5’UTR microsatellite locus had a significant additive effect on carcass weight (CW) and average daily gain (ADG). The 19-TG allele had a significantly desirable effect on these traits. We proposed a translational hypothesis that the association is due to differences in the secondary structure of GHSR1b mRNA among the GHSR1a gene haplotypes. We also examined age-related changes in the expressions of GHSR1a and GHSR1b in many cattle tissues. The GHSR1a mRNA expression in the arcuate nucleus of postweaning calves was more than 10-fold higher than those of pre-weaning calves and cows. In peripheral tissues, there were 3 marked differences in mRNA expression between cattle, humans and mice, as follows: (1) the GHSR1a mRNA expression in the liver is high in cattle and very low in humans and mice; (2) the GHSR1b mRNA expression in the liver is low in cattle and high in humans; (3) the GHSR1b mRNA expression in the pancreas is very high in cattle.