doi:10.1111/j.1365-2052.2011.02211.x 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 E. W. Berkowicz*, D. A. Magee*, D. P. Berry † , K. M. Sikora ‡,1 , D. J. Howard § , M. P. Mullen § , R. D. Evans ¶ , C. Spillane ‡,1 and D. E. MacHugh* , ** *Animal Genomics Laboratory, UCD School of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland. † Moorepark Dairy Production Research Centre, Teagasc, Fermoy, Co. Cork, Ireland. ‡ Genetics and Biotechnology Laboratory, Department of Biochemistry, University College Cork, Cork, Ireland. § Animal Production Research Centre, Teagasc, Mellows Campus, Athenry, Co. Galway, Ireland. ¶ Irish Cattle Breeding Federation, Highfield House, Bandon, Co. Cork, Ireland. **UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland Summary 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. Keywords Bos, genetic imprinting, IGF2R, performance trait, single nucleotide polymor- phism. Genetic imprinting, a form of epigenetic regulation, results in the preferential monoallelic expression of autosomal genes in a parent-of-origin manner of at least 100 mam- malian genes, most of which play pivotal roles in directing pre- and post-natal mammalian growth and development (Feil 2009). While most studies of imprinted genes have focussed on mouse and human disease models, there is accumulating evidence suggesting that imprinted loci underlie performance in domesticated animals and hence Address for correspondence David E. MacHugh; Animal Genomics Laboratory, UCD School of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Belfield, Dublin 4, Ireland. E-mail: david.machugh@ucd.ie 1 Present address: Genetics and Biotechnology Laboratory, Centre for Chromosome Biology, National University of Ireland Galway, Ireland. Accepted for publication 2 February 2011 Ó 2011 The Authors, Animal Genetics Ó 2011 Stichting International Foundation for Animal Genetics 1