Skip to main content Accessibility help

A catalogue of validated single nucleotide polymorphisms in bovine orthologs of mammalian imprinted genes and associations with beef production traits

  • D. A. Magee (a1), E. W. Berkowicz (a1), K. M. Sikora (a2), D. P. Berry (a3), S. D. E. Park (a1), A. K. Kelly (a1), T. Sweeney (a1), D. A. Kenny (a1), R. D. Evans (a4), B. W. Wickham (a4), C. Spillane (a2) and D. E. MacHugh (a1) (a5)...


Genetic (or ‘genomic’) imprinting, a feature of approximately 100 mammalian genes, results in monoallelic expression from one of the two parentally inherited chromosomes. To date, most studies have been directed on imprinted genes in murine or human models; however, there is burgeoning interest in the effects of imprinted genes in domestic livestock species. In particular, attention has focused on imprinted genes that influence foetal growth and development and that are associated with several economically important production traits in cattle, sheep and pigs. We have re-sequenced regions in 20 candidate bovine imprinted genes in order to validate single nucleotide polymorphisms (SNPs) that may influence important production traits in cattle. Putative SNPs detected via re-sequencing were subsequently re-formatted for high-throughput SNP genotyping in 185 cattle samples comprising 138 performance-tested European Bos taurus (all Limousin bulls), 29 African B. taurus and 18 Indian B. indicus samples. Analysis of the resulting genotypic data identified 117 validated SNPs. Preliminary genotype–phenotype association analyses using 83 SNPs that were polymorphic in the Limousin samples with minor allele frequencies ⩾0.05 revealed significant associations between two candidate bovine imprinted genes and a range of important beef production traits: average daily gain, average feed intake, live weight, feed conversion ratio, residual feed intake and residual gain. These genes were the Ras protein-specific guanine nucleotide releasing factor gene (RASGRF1) and the zinc finger, imprinted 2 gene (ZIM2). Despite the relatively small sample size used in these analyses, the observed associations with production traits are supported by the purported biological function of the RASGRF1 and ZIM2 gene products. These results support the hypothesis that imprinted genes contribute significantly to important complex production traits in cattle. Furthermore, these SNPs may be usefully incorporated into future marker-assisted and genomic selection breeding schemes.


Corresponding author


Hide All
Andersson, L 2009. Genome-wide association analysis in domestic animals: a powerful approach for genetic dissection of trait loci. Genetica 136, 341349.
Arthur, PF, Archer, JA, Johnston, DJ, Herd, RM, Richardson, EC, Parnell, PF 2001. Genetic and phenotypic variance and covariance components for feed intake, feed efficiency, and other postweaning traits in Angus cattle. Journal of Animal Science 79, 28052811.
Barendse, W, Reverter, A, Bunch, RJ, Harrison, BE, Barris, W, Thomas, MB 2007. A validated whole-genome association study of efficient food conversion in cattle. Genetics 176, 18931905.
Barrett, JC, Fry, B, Maller, J, Daly, MJ 2005. Haploview: analysis and visualization of LD and haplotype map. Bioinformatics 21, 263265.
Berry, DP 2008. Improving feed efficiency in cattle with residual feed intake. In Recent advances in animal nutrition (ed. P Garnsworthy) University of Nottingham Press, Nottingham.
Bradley, DG, Magee, DA 2006. Genetics and the origins of domestic cattle. In Documenting domestication: new genetic and archaeological paradigms (ed. MA Zeder, DG Bradley, E Emshwiller and BD Smith), pp. 317328, University of California Press, Berkeley, CA, USA.
Bruford, MW, Bradley, DG, Luikart, G 2003. DNA markers reveal the complexity of livestock domestication. Nature Reviews Genetics 4, 900910.
Charlier, C, Coppieters, W, Rollin, F, Desmecht, D, Agerholm, JS, Cambisano, N, Carta, E, Dardano, S, Dive, M, Fasquelle, C, Frennet, JC, Hanset, R, Hubin, X, Jorgensen, C, Karim, L, Kent, M, Harvey, K, Pearce, BR, Simon, P, Tama, N, Nie, H, Vandeputte, S, Lien, S, Longeri, M, Fredholm, M, Harvey, RJ, Georges, M 2008. Highly effective SNP-based association mapping and management of recessive defects in livestock. Nature Genetics 40, 449454.
Chen, S, Lin, BZ, Baig, M, Mitra, B, Lopes, RJ, Santos, AM, Magee, DA, Azevedo, M, Tarroso, P, Sasazaki, S, Ostrowski, S, Mahgoub, O, Chaudhuri, TK, Zhang, YP, Costa, V, Royo, LJ, Goyache, F, Luikart, G, Boivin, N, Fuller, DQ, Mannen, H, Bradley, DG, Beja-Pereira, A 2010. Zebu cattle are an exclusive legacy of the South Asia neolithic. Molecular Biology and Evolution 27, 16.
Cheng, HC, Zhang, FW, Jiang, CD, Li, FE, Xiong, YZ, Deng, CY 2008. Isolation and imprinting analysis of the porcine DLX5 gene and its association with carcass traits. Animal Genetics 39, 395399.
Clapcott, SJ, Peters, J, Orban, PC, Brambilla, R, Graham, CF 2003. Two ENU-induced mutations in Rasgrf1 and early mouse growth retardation. Mammalian Genome 14, 495505.
Cockett, NE, Smit, MA, Bidwell, CA, Segers, K, Hadfield, TL, Snowder, GD, Georges, M, Charlier, C 2005. The callipyge mutation and other genes that affect muscle hypertrophy in sheep. Genetics Selection Evolution 37 (suppl. 1), S6581.
Cole, JB, VanRaden, PM, O’Connell, JR, Van Tassell, CP, Sonstegard, TS, Schnabel, RD, Taylor, JF, Wiggans, GR 2009. Distribution and location of genetic effects for dairy traits. Journal of Dairy Science 92, 29312946.
Crowley, JJ, McGee, M, Kenny, DA, JrCrews, DH, Evans, RD, Berry, DP 2010. Phenotypic and genetic parameters for different measures of feed efficiency in different breeds of Irish performance-tested beef bulls. Journal of Animal Science 88, 885894.
da Rocha, ST, Edwards, CA, Ito, M, Ogata, T, Ferguson-Smith, AC 2008. Genomic imprinting at the mammalian Dlk1-Dio3 domain. Trends in Genetics 24, 306316.
de Koning, DJ, Bovenhuis, H, van Arendonk, JA 2002. On the detection of imprinted quantitative trait loci in experimental crosses of outbred species. Genetics 161, 931938.
de Koning, DJ, Rattink, AP, Harlizius, B, van Arendonk, JA, Brascamp, EW, Groenen, MA 2000. Genome-wide scan for body composition in pigs reveals important role of imprinting. Proceedings of the National Academy of Sciences of the United States of America 97, 79477950.
Drake, NM, Park, YJ, Shirali, AS, Cleland, TA, Soloway, PD 2009. Imprint switch mutations at Rasgrf1 support conflict hypothesis of imprinting and define a growth control mechanism upstream of IGF1. Mammalian Genome 20, 654663.
Duthie, CA, Simm, G, Perez-Enciso, M, Doeschl-Wilson, A, Kalm, E, Knap, PW, Roehe, R 2009. Genomic scan for quantitative trait loci of chemical and physical body composition and deposition on pig chromosome X including the pseudoautosomal region of males. Genetics Selection Evolution 41, 27.
Elsik, CG, Tellam, RL, Worley, KC, Gibbs, RA, Muzny, DM, Weinstock, GM,, et al. 2009. The genome sequence of taurine cattle: a window to ruminant biology and evolution. Science 324, 522528.
Fan, LQ, Bailey, DRC, Shannon, NH 1995. Genetic parameter estimation of postweaning gain, feed intake and feed efficiency for Hereford and Angus bulls fed two different diets. Journal of Animal Science 73, 365372.
Feil, R 2009. Epigenetic asymmetry in the zygote and mammalian development. International Journal of Developmental Biology 53, 191201.
Frazer, KA, Murray, SS, Schork, NJ, Topol, EJ 2009. Human genetic variation and its contribution to complex traits. Nature Reviews. Genetics 10, 241251.
Freking, BA, Murphy, SK, Wylie, AA, Rhodes, SJ, Keele, JW, Leymaster, KA, Jirtle, RL, Smith, TP 2002. Identification of the single base change causing the callipyge muscle hypertrophy phenotype, the only known example of polar overdominance in mammals. Genome Research 12, 14961506.
Georges, M, Charlier, C, Cockett, N 2003. The callipyge locus: evidence for the trans interaction of reciprocally imprinted genes. Trends in Genetics 19, 248252.
Gibbs, RA, Taylor, JF, Van Tassell, CP, Barendse, W, Eversole, KA, Gill, CA,, et al. 2009. Genome-wide survey of SNP variation uncovers the genetic structure of cattle breeds. Science 324, 528532.
Giese, KP, Friedman, E, Telliez, JB, Fedorov, NB, Wines, M, Feig, LA, Silva, AJ 2001. Hippocampus-dependent learning and memory is impaired in mice lacking the Ras-guanine-nucleotide releasing factor 1 (Ras-GRF1). Neuropharmacology 41, 791800.
Gilmour, AR, Cullis, BR, Gogel, BJ, Welham, SJ, Thompson, R 2006. ASReml user guide. Release 2.0. VSN International Ltd, Hemel Hempsted, UK Manual. New South Wales Agriculture, Orange Agricultural Institute, Orange, Australia.
Goddard, ME, Hayes, BJ 2009. Mapping genes for complex traits in domestic animals and their use in breeding programmes. Nature Reviews. Genetics 10, 381391.
Heaton, MP, Grosse, WM, Kappes, SM, Keele, JW, Chitko-McKown, CG, Cundiff, LV, Braun, A, Little, DP, Laegreid, WW 2001. Estimation of DNA sequence diversity in bovine cytokine genes. Mammalian Genome 12, 3237.
Hegarty, RS, Goopy, JP, Herd, RM, McCorkell, B 2007. Cattle selected for lower residual feed intake have reduced daily methane production. Journal of Animal Science 85, 14791486.
Hill, WG, Robertson, A 1968. Linkage disequilibrium in finite populations. Theoretical and Applied Genetics 38, 226231.
Holl, JW, Cassady, JP, Pomp, D, Johnson, RK 2004. A genome scan for quantitative trait loci and imprinted regions affecting reproduction in pigs. Journal of Animal Science 82, 34213429.
Karlskov-Mortensen, P, Bruun, CS, Braunschweig, MH, Sawera, M, Markljung, E, Enfalt, AC, Hedebro-Velander, I, Josell, A, Lindahl, G, Lundstrom, K, von Seth, G, Jorgensen, CB, Andersson, L, Fredholm, M 2006. Genome-wide identification of quantitative trait loci in a cross between Hampshire and Landrace I: carcass traits. Animal Genetics 37, 156162.
Khatib, H 2004. Imprinting of Nesp55 gene in cattle. Mammalian Genome 15, 663667.
Kim, J, Bergmann, A, Lucas, S, Stone, R, Stubbs, L 2004a. Lineage-specific imprinting and evolution of the zinc-finger gene ZIM2. Genomics 84, 4758.
Kim, KS, Kim, JJ, Dekkers, JC, Rothschild, MF 2004b. Polar overdominant inheritance of a DLK1 polymorphism is associated with growth and fatness in pigs. Mammalian Genome 15, 552559.
Koch, RM, Swiger, LA, Chambers, D, Gregory, KE 1963. Efficiency of feed use in beef cattle. Journal of Animal Science 22, 486494.
Kruglyak, L, Nickerson, DA 2001. Variation is the spice of life. Nature Genetics 27, 234236.
Mackay, TF, Stone, EA, Ayroles, JF 2009. The genetics of quantitative traits: challenges and prospects. Nature Reviews. Genetics 10, 565577.
Markljung, E, Braunschweig, MH, Karlskov-Mortensen, P, Bruun, CS, Sawera, M, Cho, IC, Hedebro-Velander, I, Josell, A, Lundstrom, K, von Seth, G, Jorgensen, CB, Fredholm, M, Andersson, L 2008. Genome-wide identification of quantitative trait loci in a cross between Hampshire and Landrace II: meat quality traits. BMC Genetics 9, 22.
Matukumalli, LK, Lawley, CT, Schnabel, RD, Taylor, JF, Allan, MF, Heaton, MP, O’Connell, J, Moore, SS, Smith, TP, Sonstegard, TS, Van Tassell, CP 2009. Development and characterization of a high density SNP genotyping assay for cattle. PLoS One 4, e5350.
McGrath, J, Solter, D 1984. Completion of mouse embryogenesis requires both the maternal and paternal genomes. Cell 37, 179183.
Morison, IM, Ramsay, JP, Spencer, HG 2005. A census of mammalian imprinting. Trends Genetics 21, 457465.
Murphy, SK, Nolan, CM, Huang, Z, Kucera, KS, Freking, BA, Smith, TP, Leymaster, KA, Weidman, JR, Jirtle, RL 2006. Callipyge mutation affects gene expression in cis: a potential role for chromatin structure. Genome Research 16, 340346.
Nezer, C, Moreau, L, Wagenaar, D, Georges, M 2002. Results of a whole genome scan targeting QTL for growth and carcass traits in a Pietrain x Large White intercross. Genetics Selection Evolution 34, 371387.
Nezer, C, Moreau, L, Brouwers, B, Coppieters, W, Detilleux, J, Hanset, R, Karim, L, Kvasz, A, Leroy, P, Georges, M 1999. An imprinted QTL with major effect on muscle mass and fat deposition maps to the IGF2 locus in pigs. Nature Genetics 21, 155156.
Park, SDE 2001. Trypanotolerance in West African cattle and the population genetic effects of selection. PhD thesis, University of Dublin, Trinity College.
Patten, MM, Haig, D 2008. Reciprocally imprinted genes and the response to selection on one sex. Genetics 179, 13891394.
Plass, C, Shibata, H, Kalcheva, I, Mullins, L, Kotelevtseva, N, Mullins, J, Kato, R, Sasaki, H, Hirotsune, S, Okazaki, Y, Held, WA, Hayashizaki, Y, Chapman, VM 1996. Identification of Grf1 on mouse chromosome 9 as an imprinted gene by RLGS-M. Nature Genetics 14, 106109.
Rattink, AP, De Koning, DJ, Faivre, M, Harlizius, B, van Arendonk, JA, Groenen, MA 2000. Fine mapping and imprinting analysis for fatness trait QTLs in pigs. Mammalian Genome 11, 656661.
Reik, W, Walter, J 2001. Genomic imprinting: parental influence on the genome. Nature Reviews. Genetics 2, 2132.
Ron, M, Weller, JI 2007. From QTL to QTN identification in livestock--winning by points rather than knock-out: a review. Animal Genetics 38, 429439.
Ruvinsky, A 1999. Basics of gametic imprinting. Journal of Animal Science 77 (suppl. 2), 228237.
Schnekel, FS, Miller, SP, Wilton, JW 2004. Genetic parameters and breed differences for feed efficiency, growth and body composition traits of young beef bulls. Canadian Journal of Animal Science 84, 177185.
Sellner, EM, Kim, JW, McClure, MC, Taylor, KH, Schnabel, RD, Taylor, JF 2007. Applications of genomic information in livestock. Journal of Animal Science 85, 31483158.
Sherman, EL, Nkrumah, JD, Murdoch, BM, Moore, SS 2008. Identification of polymorphisms influencing feed intake and efficiency in beef cattle. Animal Genetics 39, 225231.
Smit, M, Segers, K, Carrascosa, LG, Shay, T, Baraldi, F, Gyapay, G, Snowder, G, Georges, M, Cockett, N, Charlier, C 2003. Mosaicism of Solid Gold supports the causality of a noncoding A-to-G transition in the determinism of the callipyge phenotype. Genetics 163, 453456.
Surani, MA, Barton, SC, Norris, ML 1984. Development of reconstituted mouse eggs suggests imprinting of the genome during gametogenesis. Nature 308, 548550.
Tamura, K, Dudley, J, Nei, M, Kumar, S 2007. MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Molecular Biology Evolution 24, 15961599.
Uemoto, Y, Sato, S, Ohnishi, C, Terai, S, Komatsuda, A, Kobayashi, E 2009. The effects of single and epistatic quantitative trait loci for fatty acid composition in a Meishan x Duroc crossbred population. Journal of Animal Science 87, 34703476.
Van den Veyver, IB, Norman, B, Tran, CQ, Bourjac, J, Slim, R 2001. The human homologue (PEG3) of the mouse paternally expressed gene 3 (Peg3) is maternally imprinted but not mutated in women with familial recurrent hydatidiform molar pregnancies. Journal of Society for Gynecologic and Investigation 8, 305313.
Van Laere, AS, Nguyen, M, Braunschweig, M, Nezer, C, Collette, C, Moreau, L, Archibald, AL, Haley, CS, Buys, N, Tally, M, Andersson, G, Georges, M, Andersson, L 2003. A regulatory mutation in IGF2 causes a major QTL effect on muscle growth in the pig. Nature 425, 832836.
Van Tassell, CP, Smith, TP, Matukumalli, LK, Taylor, JF, Schnabel, RD, Lawley, CT, Haudenschild, CD, Moore, SS, Warren, WC, Sonstegard, TS 2008. SNP discovery and allele frequency estimation by deep sequencing of reduced representation libraries. Nature Methods 5, 247252.
Williams, JL, Dunner, S, Valentini, A, Mazza, R, Amarger, V, Checa, ML, Crisa, A, Razzaq, N, Delourme, D, Grandjean, F, Marchitelli, C, Garcia, D, Gomez, RP, Negrini, R, Marsan, PA, Leveziel, H 2009. Discovery, characterization and validation of single nucleotide polymorphisms within 206 bovine genes that may be considered as candidate genes for beef production and quality. Animal Genetics 40, 486491.


Type Description Title
Supplementary materials

Magee Supplementary Material

 Unknown (111 KB)
111 KB


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed