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. 2004 Aug;167(4):1873–1881. doi: 10.1534/genetics.103.022749

Evidence for multiple alleles at the DGAT1 locus better explains a quantitative trait locus with major effect on milk fat content in cattle.

Christa Kühn 1, Georg Thaller 1, Andreas Winter 1, Olaf R P Bininda-Emonds 1, Bernhard Kaupe 1, Georg Erhardt 1, Jörn Bennewitz 1, Manfred Schwerin 1, Ruedi Fries 1
PMCID: PMC1470998  PMID: 15342525

Abstract

A quantitative trait locus (QTL) for milk fat percentage has been mapped consistently to the centromeric region of bovine chromosome 14 (BTA14). Two independent studies have identified the nonconservative mutation K232A in the acylCoA-diacylglycerol-acyltransferase 1 (DGAT1) gene as likely to be causal for the observed variation. Here we provide evidence for additional genetic variability at the same QTL that is associated with milk fat percentage variation within the German Holstein population. Namely, we show that alleles of the DGAT1 promoter derived from the variable number of tandem repeat (VNTR) polymorphism are associated with milk fat content in animals homozygous for the allele 232A at DGAT1. Our results present another example for more than two trait-associated alleles being involved in a major gene effect on a quantitative trait. The segregation of multiple alleles affecting milk production traits at the QTL on BTA14 has to be considered whenever marker-assisted selection programs are implemented in dairy cattle. Due to the presence of a potential transcription factor binding site in the 18mer element of the VNTR, the variation in the number of tandem repeats of the 18mer element might be causal for the variability in the transcription level of the DGAT1 gene.

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Selected References

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  1. Blott Sarah, Kim Jong-Joo, Moisio Sirja, Schmidt-Küntzel Anne, Cornet Anne, Berzi Paulette, Cambisano Nadine, Ford Christine, Grisart Bernard, Johnson Dave. Molecular dissection of a quantitative trait locus: a phenylalanine-to-tyrosine substitution in the transmembrane domain of the bovine growth hormone receptor is associated with a major effect on milk yield and composition. Genetics. 2003 Jan;163(1):253–266. doi: 10.1093/genetics/163.1.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Boichard Didier, Grohs Cécile, Bourgeois Florence, Cerqueira Frédérique, Faugeras Rémi, Neau André, Rupp Rachel, Amigues Yves, Boscher Marie Yvonne, Levéziel Hubert. Detection of genes influencing economic traits in three French dairy cattle breeds. Genet Sel Evol. 2003 Jan-Feb;35(1):77–101. doi: 10.1186/1297-9686-35-1-77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cases S., Smith S. J., Zheng Y. W., Myers H. M., Lear S. R., Sande E., Novak S., Collins C., Welch C. B., Lusis A. J. Identification of a gene encoding an acyl CoA:diacylglycerol acyltransferase, a key enzyme in triacylglycerol synthesis. Proc Natl Acad Sci U S A. 1998 Oct 27;95(22):13018–13023. doi: 10.1073/pnas.95.22.13018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Churchill G. A., Doerge R. W. Empirical threshold values for quantitative trait mapping. Genetics. 1994 Nov;138(3):963–971. doi: 10.1093/genetics/138.3.963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ciobanu D., Bastiaansen J., Malek M., Helm J., Woollard J., Plastow G., Rothschild M. Evidence for new alleles in the protein kinase adenosine monophosphate-activated gamma(3)-subunit gene associated with low glycogen content in pig skeletal muscle and improved meat quality. Genetics. 2001 Nov;159(3):1151–1162. doi: 10.1093/genetics/159.3.1151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dunner Susana, Miranda M. Eugenia, Amigues Yves, Cañn Javier, Georges Michel, Hanset Roger, Williams John, Ménissier François. Haplotype diversity of the myostatin gene among beef cattle breeds. Genet Sel Evol. 2003 Jan-Feb;35(1):103–118. doi: 10.1186/1297-9686-35-1-103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Farnir Frédéric, Grisart Bernard, Coppieters Wouter, Riquet Juliette, Berzi Paulette, Cambisano Nadine, Karim Latifa, Mni Myriam, Moisio Sirja, Simon Patricia. Simultaneous mining of linkage and linkage disequilibrium to fine map quantitative trait loci in outbred half-sib pedigrees: revisiting the location of a quantitative trait locus with major effect on milk production on bovine chromosome 14. Genetics. 2002 May;161(1):275–287. doi: 10.1093/genetics/161.1.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Glazier Anne M., Nadeau Joseph H., Aitman Timothy J. Finding genes that underlie complex traits. Science. 2002 Dec 20;298(5602):2345–2349. doi: 10.1126/science.1076641. [DOI] [PubMed] [Google Scholar]
  9. Jeon J. T., Carlborg O., Törnsten A., Giuffra E., Amarger V., Chardon P., Andersson-Eklund L., Andersson K., Hansson I., Lundström K. A paternally expressed QTL affecting skeletal and cardiac muscle mass in pigs maps to the IGF2 locus. Nat Genet. 1999 Feb;21(2):157–158. doi: 10.1038/5938. [DOI] [PubMed] [Google Scholar]
  10. Kühn Ch, Bennewitz J., Reinsch N., Xu N., Thomsen H., Looft C., Brockmann G. A., Schwerin M., Weimann C., Hiendleder S. Quantitative trait loci mapping of functional traits in the German Holstein cattle population. J Dairy Sci. 2003 Jan;86(1):360–368. doi: 10.3168/jds.s0022-0302(03)73614-5. [DOI] [PubMed] [Google Scholar]
  11. Looft C., Reinsch N., Karall-Albrecht C., Paul S., Brink M., Thomsen H., Brockmann G., Kühn C., Schwerin M., Kalm E. A mammary gland EST showing linkage disequilibrium to a milk production QTL on bovine Chromosome 14. Mamm Genome. 2001 Aug;12(8):646–650. doi: 10.1007/s003350020003. [DOI] [PubMed] [Google Scholar]
  12. Mallard B. A., Leslie K. E., Dekkers J. C., Hedge R., Bauman M., Stear M. J. Differences in bovine lymphocyte antigen associations between immune responsiveness and risk of disease following intramammary infection with Staphylococcus aureus. J Dairy Sci. 1995 Sep;78(9):1937–1944. doi: 10.3168/jds.S0022-0302(95)76819-9. [DOI] [PubMed] [Google Scholar]
  13. Meegalla Rupalie L., Billheimer Jeffrey T., Cheng Dong. Concerted elevation of acyl-coenzyme A:diacylglycerol acyltransferase (DGAT) activity through independent stimulation of mRNA expression of DGAT1 and DGAT2 by carbohydrate and insulin. Biochem Biophys Res Commun. 2002 Nov 1;298(3):317–323. doi: 10.1016/s0006-291x(02)02466-x. [DOI] [PubMed] [Google Scholar]
  14. Nezer C., Moreau L., Brouwers B., Coppieters W., Detilleux J., Hanset R., Karim L., Kvasz A., Leroy P., Georges M. An imprinted QTL with major effect on muscle mass and fat deposition maps to the IGF2 locus in pigs. Nat Genet. 1999 Feb;21(2):155–156. doi: 10.1038/5935. [DOI] [PubMed] [Google Scholar]
  15. Ogura Y., Bonen D. K., Inohara N., Nicolae D. L., Chen F. F., Ramos R., Britton H., Moran T., Karaliuskas R., Duerr R. H. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001 May 31;411(6837):603–606. doi: 10.1038/35079114. [DOI] [PubMed] [Google Scholar]
  16. Riquet J., Coppieters W., Cambisano N., Arranz J. J., Berzi P., Davis S. K., Grisart B., Farnir F., Karim L., Mni M. Fine-mapping of quantitative trait loci by identity by descent in outbred populations: application to milk production in dairy cattle. Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):9252–9257. doi: 10.1073/pnas.96.16.9252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Smith S. J., Cases S., Jensen D. R., Chen H. C., Sande E., Tow B., Sanan D. A., Raber J., Eckel R. H., Farese R. V., Jr Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat Genet. 2000 May;25(1):87–90. doi: 10.1038/75651. [DOI] [PubMed] [Google Scholar]
  18. Sobel E., Lange K. Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics. Am J Hum Genet. 1996 Jun;58(6):1323–1337. [PMC free article] [PubMed] [Google Scholar]
  19. Spelman R. J., Ford C. A., McElhinney P., Gregory G. C., Snell R. G. Characterization of the DGAT1 gene in the New Zealand dairy population. J Dairy Sci. 2002 Dec;85(12):3514–3517. doi: 10.3168/jds.S0022-0302(02)74440-8. [DOI] [PubMed] [Google Scholar]
  20. Thaller G., Krämer W., Winter A., Kaupe B., Erhardt G., Fries R. Effects of DGAT1 variants on milk production traits in German cattle breeds. J Anim Sci. 2003 Aug;81(8):1911–1918. doi: 10.2527/2003.8181911x. [DOI] [PubMed] [Google Scholar]
  21. VanRaden P. M., Wiggans G. R. Derivation, calculation, and use of national animal model information. J Dairy Sci. 1991 Aug;74(8):2737–2746. doi: 10.3168/jds.S0022-0302(91)78453-1. [DOI] [PubMed] [Google Scholar]
  22. Vaulont S., Vasseur-Cognet M., Kahn A. Glucose regulation of gene transcription. J Biol Chem. 2000 Oct 13;275(41):31555–31558. doi: 10.1074/jbc.R000016200. [DOI] [PubMed] [Google Scholar]
  23. Weller J. I., Kashi Y., Soller M. Power of daughter and granddaughter designs for determining linkage between marker loci and quantitative trait loci in dairy cattle. J Dairy Sci. 1990 Sep;73(9):2525–2537. doi: 10.3168/jds.S0022-0302(90)78938-2. [DOI] [PubMed] [Google Scholar]
  24. Winter Andreas, Krämer Wolfgang, Werner Fabian A. O., Kollers Sonja, Kata Srinivas, Durstewitz Gregor, Buitkamp Johannes, Womack James E., Thaller Georg, Fries Ruedi. Association of a lysine-232/alanine polymorphism in a bovine gene encoding acyl-CoA:diacylglycerol acyltransferase (DGAT1) with variation at a quantitative trait locus for milk fat content. Proc Natl Acad Sci U S A. 2002 Jun 20;99(14):9300–9305. doi: 10.1073/pnas.142293799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Yang X., Fyodorov D., Deneris E. S. Transcriptional analysis of acetylcholine receptor alpha 3 gene promoter motifs that bind Sp1 and AP2. J Biol Chem. 1995 Apr 14;270(15):8514–8520. doi: 10.1074/jbc.270.15.8514. [DOI] [PubMed] [Google Scholar]

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