Single nucleotide polymorphisms in the imprinted bovine insulin‐like growth factor 2 receptor gene (IGF2R) are associated with body size traits in Irish Holstein‐Friesian cattle

Abstract

The regulation of the bioavailability of insulin-like growth factors (IGFs) is critical for normal mammalian growth and development. The imprinted insulin-like growth factor 2 receptor gene (IGF2R) encodes a transmembrane protein receptor that acts to sequester and degrade excess circulating insulin-like growth factor 2 (IGF-II) - a potent foetal mitogen - and is considered an important inhibitor of growth. Consequently, IGF2R may serve as a candidate gene underlying important growth- and body-related quantitative traits in domestic mammalian livestock. In this study, we have quantified genotype-phenotype associations between three previously validated intronic bovine IGF2R single nucleotide polymorphisms (SNPs) (IGF2R:g.64614T>C, IGF2R:g.65037T>C and IGF2R:g.86262C>T) and a range of performance traits in 848 progeny-tested Irish Holstein-Friesian artificial insemination sires. Notably, all three polymorphisms analysed were associated (P ≤ 0.05) with at least one of a number of performance traits related to animal body size: angularity, body depth, chest width, rump width, and animal stature. In addition, the C-to-T transition at the IGF2R:g.65037T>C polymorphism was positively associated with cow carcass weight and angularity. Correction for multiple testing resulted in the retention of two genotype-phenotype associations (animal stature and rump width). None of the SNPs analysed were associated with any of the milk traits examined. Analysis of pairwise r(2) measures of linkage disequilibrium between all three assayed SNPs ranged between 0.41 and 0.79, suggesting that some of the observed SNP associations with performance may be independent. To our knowledge, this is one of the first studies demonstrating associations between IGF2R polymorphisms and growth- and body-related traits in cattle. These results also support the increasing body of evidence that imprinted genes harbour polymorphisms that contribute to heritable variation in phenotypic traits in domestic livestock species.

Polymorphism discovery and allele frequency estimation using high-throughput DNA sequencing of target-enriched pooled DNA samples

“…This included analysis of genotypes previously reported by this group in IGF1 [4], IGF2R, IGF2 [31,32], GH1 [5] and GHR [7]. …”

Comparative epigenetics: relevance to the regulation of production and health traits in cattle

“…Differential expression of IGF2 already was known to be prevalent in the pathogenesis of the developmental disease BWS (Waterland et al 2006), and this study revealed epigenetic changes at the gene locus as a causative factor. As discussed earlier, this gene has been associated with several important traits in cattle, such as oocyte competency and milk yield (Flisikowski et al 2007;Fagundes et al 2011;Berkowicz et al 2012). Epigenetic changes in this gene could therefore have important implications for regulation of fertility and production traits in cattle.…”

“…Loss of imprinting at this gene has been associated with growth disorders in humans as well as the onset of diseases such as cancer (Chao & D'Amore 2008). Relevantly, both this gene and its receptor (IGF2R) also have been shown to influence several complex performance traits in cattle, including body size and carcass traits (Imumorin et al 2011;Magee et al 2011;Berkowicz et al 2012;Sikora et al 2012). However, genetic improvement schemes in livestock assume that the expression of desirable traits is independent of parental origin (de Vries et al 1994).…”

“…Imprinting of murine Igf2 was lost in animals fed a synthetic diet deficient in methyl donors including vitamin B 12 (Waterland et al 2006) The IGF2 gene is associated with milk production and carcass traits in cattle (Flisikowski et al 2007;Berkowicz et al 2012) and therefore dietary strategies could be used to influence the epigenetic regulation of this gene and enhance capture of valuable phenotypes Behaviour Glucocorticoid receptor (GR-A) also known as nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) (NR3C1)…”

Polymorphism analysis of the intron one of insulin-like growth factor 2 receptor gene (IGF2R) in FFRC strain common carp (Cyprinus carpio L.) and its relationship with growth performance

“…FFRC strain common carp IGF2R intron one polymorphisms and effect of sex on body weight Berkowicz et al (2011) quantified genotype-phenotype associations between 3 intronic bovine IGF2R SNPs and body size traits in Irish Holstein-Friesian sires. Kaku et al (2007) also observed a significant difference in birth weight among the 3 neonatal c.901C>G genotypes of the IGF2R gene (i.e., CC, CG, and GG).…”