A missense mutation in the bovine leptin receptor gene is associated with leptin concentrations during late pregnancy.

The leptin receptor (LEPR) gene consists of 20 exons divided over 1.75 Mb. Parts of bovine LEPR exon 4 (79 bp), exon 11 (95 bp) and exon 20 (513 bp) of 20 cows (Holstein-Friesian) were sequenced (AJ580799; AJ580800; AJ580801) in an attempt to find polymorphisms. In exons 4 and 11 no SNPs were found. In exon 20, a T to C missense mutation was found at nucleotide 115, which causes an amino acid substitution at residue 945 (T945M). Frequencies for alleles C and T were 0.93 and 0.07 respectively, in a population of 323 Holstein-Friesian cows and TT animals were not detected. Using genotypes of these cows an association study was performed for leptin concentrations during late pregnancy and lactation. Leptin concentrations were determined by radioimmunoassay (RIA). The T945M mutation showed an association with circulating leptin concentrations only during late pregnancy (P < 0.05) but not during lactation (P > 0.05). The CC genotype had higher concentrations than the CT genotype during this period. A combined effect with previously described leptin polymorphisms on prepartum leptin concentrations was observed, with one genotype combination having significantly lower levels of leptin up to 50 days, but interaction effects were not significant. The T945M polymorphism may have induced a structural change in the intracellular domain of the LEPR, which may have influenced the signal transduction pathway. However, the effect was found only for the heterozygous genotype because the TT genotype was not detected in this population of 323 Holstein-Friesian cows.