Polymorphisms in the bovine leptin gene associated with perinatal mortality in Holstein-Friesian heifers

J.S Brickell,G.E Pollott,A.M Clempson,N Otter,D.C Wathes

doi:10.3168/jds.2009-2457

Abstract

Leptin is an important regulator of fetal and placental growth. This study evaluated the association of single nucleotide polymorphisms (SNP) in the leptin gene with perinatal mortality (stillbirths and mortality within 24h of parturition) in 385 Holstein-Friesian heifers on 18 dairy farms in the United Kingdom. The 3 SNP evaluated were exon 2FB, UASMS1, and UASMS2. The mean age at first calving was 27.0±0.2 mo. Associations between each SNP and perinatal mortality (calf alive or dead) were tested using a generalized linear model that included herd-year-season, calf sex, age at first calving, and age and pedigree of the dam. The overall level of perinatal mortality in the population was 16.9%, with significant allelic substitution effects for exon 2FB and UASMS1. These 2 SNP were in close linkage disequilibrium with each other (r2=0.98) but not with UASMS2 (r2=0.10). For exon 2FB, perinatal mortality was similar between heifers carrying the CT and TT alleles (20%), but was higher than in heifers carrying the CC allele (11%). For UASMS1, mortality was 21% with the CC and CT alleles but only 10% with the TT allele. No associations of perinatal mortality with SNP were found in the UASMS2 data set, possibly influenced by the low frequency (2%) of the TT genotype. No significant effects of herd-year-season, age at first calving, or calf sex were found. In conclusion, polymorphisms in the leptin gene were associated with 2-fold differences in perinatal mortality in dairy heifers.

Highlights

Leptin, a protein hormone synthesized and secreted primarily by white adipocytes, has been found to be an important physiological marker of BW, feed intake, energy expenditure, and reproductive function in hu-In cattle, plasma leptin concentration is high during late pregnancy and decreases at parturition (Block et al, 2001; Liefers et al, 2003)
The single nucleotide polymorphisms (SNP) UASMS1 and exon 2FB were shown to be in close linkage disequilibrium (LD), with an r2 value of 0.98
In the case of UASMS1, the TT allele had a lower level of mortality than both the CC and CT alleles, which themselves were not different from each other. These data show that 2 polymorphisms in the leptin gene are both associated with differences in perinatal mortality in a British population of Holstein-Friesian heifers

Summary

Introduction

A protein hormone synthesized and secreted primarily by white adipocytes, has been found to be an important physiological marker of BW, feed intake, energy expenditure, and reproductive function in hu-In cattle, plasma leptin concentration is high during late pregnancy and decreases at parturition (Block et al, 2001; Liefers et al, 2003). Unlike in humans and mice, the ruminant placenta has negligible expression of leptin mRNA throughout gestation, indicating that the placenta is not a major source of circulating leptin during late pregnancy (Block et al, 2001; Ehrhardt et al, 2001; Thomas et al, 2001). Perinatal mortality (defined as stillbirths and mortality within 24 h of parturition) is a major contributing factor to heifer loss in the dairy industry. There is some evidence for an increasing prevalence of perinatal mortality in Holstein populations (Harbers et al, 2000; Meyer et al, 2001; Steinbock et al, 2003); an increased proportion of this loss does not appear to be associated with the traditional risk factors (Mee et al, 2008). Determination of which genotypes may be associated with calf mortality at parturition offers the possibility of future genetic selection against this adverse trait

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