Mammalian Genome

, Volume 15, Issue 7, pp 552–559

Polar overdominant inheritance of a DLK1 polymorphism is associated with growth and fatness in pigs

  • Kwan-Suk Kim
  • Jong-Joo Kim
  • Jack C.M. Dekkers
  • Max F. Rothschild
Article

Abstract

The polar overdominance model of inheritance was proposed to explain the non-Mendelian expression of callipyge muscular hypertrophy in sheep. The callipyge locus (CLPG) maps to the distal portion of ovine Chromosome 18 within the DLK1GTL2 region and corresponds to human Chromosome 14q32, where uniparental disomy (UPD) of the region is associated with multiple congenital anomalies, including growth retardation and obesity. We investigated the porcine DLK1GTL2 region in a cross of two pig breeds to determine if the callipyge polar overdominance is present in another species. Analyses of the parental origin of DLK1 polymorphism in the F2 offspring found that paternal inheritance of DLK1 allele 2 and maternal inheritance of the allele 1 was significantly associated with decreased fat deposition and increased lean muscle mass, while the opposite parental inheritance of these alleles was associated with slower prenatal and postnatal growth. These results suggest that the polar overdominance mode of inheritance is present in the pig chromosomal region that is homologous to the CLPG locus in sheep. Further study in pigs can provide important insights into understanding the molecular regulation of imprinted genes that are associated with human UPD14 and sheep callipyge phenotypes.

References

  1. Baldacci, PA, Richouz, V, Renard, JP, Guenet, JL, Babinet, C 1992The locus Om, responsible for the DDK syndrome, maps close to Sigje on mouse chromosome 11Mamm Genome2100105PubMedGoogle Scholar
  2. Charlier, C, Segers, K, Wagenaar, D, Karim, L, Berghmans, S,  et al. 2001aHuman–ovine comparative sequencing of a 250-kb imprinted domain encompassing the callipyge (clpg) locus and identification of six imprinted transcripts: DLK1, DAT, GTL2, PEG11, antiPEG11, and MEG8Genome Res11850862CrossRefGoogle Scholar
  3. Charlier, C, Segers, K, Karim, L, Shay, T, Gyapay, G,  et al. 2001bThe callipyge mutation enhances the expression of coregulated imprinted genes in cis without affecting their imprinting statusNat Genet27367369CrossRefGoogle Scholar
  4. Cockett, NE, Jackson, SP, Shay, TL, Farnir, F, Berghmans, S,  et al. 1996Polar overdominance at the ovine callipyge locusScience273236238PubMedGoogle Scholar
  5. Koning, DJ, Bovenhuis, H, Arendonk, JA 2002On the detection of imprinted quantitative trait loci in experimental crosses of outbred speciesGenetics161931938PubMedGoogle Scholar
  6. Fahrenkrug, SC, Freking, BA, Smith, TP 1999Genomic organization and genetic mapping of the bovine PREF-1 geneBiochem Biophys Res Commun264662667CrossRefPubMedGoogle Scholar
  7. Freking, BA, Murphy, SK, Wylie, AA, Rhodes, SJ, Keele, JW,  et al. 2002Identification of the single base change causing the callipyge muscle hypertrophy phenotype, the only known example of polar overdominance in mammalsGenome Res1214961506CrossRefPubMedGoogle Scholar
  8. Garces, C, Ruiz–Hidalgo, MJ, Bonvini, E, Goldstein, J, Laborda, J 1999Adipocyte differentiation is modulated by secreted delta-like (dlk) variants and requires the expression of membrane-associated dlkDifferentiation64103114CrossRefPubMedGoogle Scholar
  9. Georges, M, Charlier, C, Cockett, N 2003The callipyge locus: evidence for the trans interaction of reciprocally imprinted genesTrends Genet19248252CrossRefPubMedGoogle Scholar
  10. Goureau, A, Vignoles, M, Pinton, P, Gellin, J, Yerle, M 2000Improvement of comparative map between porcine chromosomes 1 and 7 and human chromosomes 6, 14, and 15 by using human YACsMamm Genome11796799CrossRefPubMedGoogle Scholar
  11. Haley, CS, Knott, SA, Elsen, JM 1994Mapping quantitative trait loci in crosses between outbred lines using least squaresGenetics13611951207PubMedGoogle Scholar
  12. Kim, JJ, Thomsen, H, Kim, KS, Rothschild, MF, Dekkers, JCM 2004A least square regression model to detect quantitative trait loci with polar overdominance in a cross of outbred breedsGenetics..submittedGoogle Scholar
  13. Kurosawa, K, Sasaki, H, Sato, Y, Yamanaka, M, Shimizu, M,  et al. 2002Paternal UPD14 is responsible for a distinctive malformation complexAm J Med Genet110268272CrossRefPubMedGoogle Scholar
  14. Lin, SP, Youngson, N, Takada, S, Seitz, H, Reik, W,  et al. 2003Asymmetric regulation of imprinting on the maternal and paternal chromosomes at the Dlkl-Gtl2 imprinted cluster on mouse chromosome 12Nat Genet3597102CrossRefPubMedGoogle Scholar
  15. Malek, M, Dekkers, JC, Lee, HK, Baas, TJ, Rothschild, MF 2001aA molecular genome scan analysis to identify chromosomal regions influencing economic traits in the pig. I. Growth and body compositionMamm Genome12630636CrossRefGoogle Scholar
  16. Malek, M, Dekkers, JC, Lee, HK, Baas, TJ, Prusa, K,  et al. 2001bA molecular genome scan analysis to identify chromosomal regions influencing economic traits in the pig. II. Meat and muscle compositionMamm Genome12637645CrossRefGoogle Scholar
  17. Moon, YS, Smas, CM, Lee, K, Villena, JA, Kim, KH,  et al. 2002Mice lacking paternally expressed Pref-1/Dlk1 display growth retardation and accelerated adiposityMol Cell Biol2255855592CrossRefPubMedGoogle Scholar
  18. Moore, T, Haig, D 1991Genomic imprinting in mammalian development: A parental tug-of-warTrends Genet74549PubMedGoogle Scholar
  19. Nezer, C, Moreau, L, Brouwers, B, Coppieters, W, Detillieux, J,  et al. 1999An imprinted QTL with major effect on muscle mass and fat deposition maps to the IGF2 locus in pigsNat Genet21155156CrossRefPubMedGoogle Scholar
  20. Schmidt, JV, Matteson, PG, Jones, BK, Guan, XJ, Tilghman, SM 2000The Dlk1 and Gtl2 genes are linked and reciprocally imprintedGenes Dev1419972002PubMedGoogle Scholar
  21. Smas, CM, Sul, HS 1993Pref-1, a protein containing EGF-like repeats, inhibits adipocyte differentiationCell73725734CrossRefPubMedGoogle Scholar
  22. Smit, M, Segers, K, Carrascosa, LG, Shay, T, Baraldi, F,  et al. 2003Mosaicism of solid gold supports the causality of a noncoding A-to-G transition in the determinism of the callipyge phenotypeGenetics163453456PubMedGoogle Scholar
  23. Sutton, VR, Shaffer, LG 2000Search for imprinted regions on chromosome 14: comparison of maternal and paternal UPD cases with cases of chromosome 14 deletionAm J Med Genet93381387CrossRefPubMedGoogle Scholar
  24. Takada, S, Tevendale, M, Baker, J, Georgiades, P, Campbell, E,  et al. 2000Delta-like and gtl2 are reciprocally expressed, differentially methylated linked imprinted genes on mouse chromosome 12Curr Biol1011351138CrossRefPubMedGoogle Scholar
  25. Wakasugi, N 1974A genetically determined incompatibility system between spermatozoa and eggs leading to embryonic death in miceJ Reprod Fertil418596PubMedGoogle Scholar
  26. Wylie, AA, Murphy, SK, Orton, TC, Jirtle, RL 2000Novel imprinted DLK1/GTL2 domain on human chromosome 14 contains motifs that mimic those implicated in IGF2/H19 regulationGenome Res1017111718CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Kwan-Suk Kim
    • 1
    • 2
  • Jong-Joo Kim
    • 1
  • Jack C.M. Dekkers
    • 1
  • Max F. Rothschild
    • 1
  1. 1.Department of Animal Science and Center for Integrated Animal GenomicsIowa State UniversityAmesUSA
  2. 2.Department of Animal ScienceMichigan State UniversityEast LansingUSA

Personalised recommendations