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. 1998 Sep;150(1):369–381. doi: 10.1093/genetics/150.1.369

Quantitative trait loci affecting body weight and fatness from a mouse line selected for extreme high growth.

G A Brockmann 1, C S Haley 1, U Renne 1, S A Knott 1, M Schwerin 1
PMCID: PMC1460298  PMID: 9725853

Abstract

Quantitative trait loci (QTL) influencing body weight were mapped by linkage analysis in crosses between a high body weight selected line (DU6) and a control line (DUKs). The two mouse lines differ in body weight by 106% and in abdominal fat weight by 100% at 42 days. They were generated from the same base population and maintained as outbred colonies. Determination of line-specific allele frequencies at microsatellite markers spanning the genome indicated significant changes between the lines on 15 autosomes and the X chromosome. To confirm these effects, a QTL analysis was performed using structured F2 pedigrees derived from crosses of a single male from DU6 with a female from DUKs. QTL significant at the genome-wide level were mapped for body weight on chromosome 11; for abdominal fat weight on chromosomes 4, 11, and 13; for abdominal fat percentage on chromosomes 3 and 4; and for the weights of liver on chromosomes 4 and 11, of kidney on chromosomes 2 and 9, and of spleen on chromosome 11. The strong effect on body weight of the QTL on chromosome 11 was confirmed in three independent pedigrees. The effect was additive and independent of sex, accounting for 21-35% of the phenotypic variance of body weight within the corresponding F2 populations. The test for multiple QTL on chromosome 11 with combined data from all pedigrees indicated the segregation of two loci separated by 36 cM influencing body weight.

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Selected References

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  1. Brockmann G., Buitkamp J., Bünger L., Epplen J. T., Schwerin M. DNA fingerprinting of trait-selected mouse lines and linkage analysis in reference families. EXS. 1993;67:403–410. doi: 10.1007/978-3-0348-8583-6_39. [DOI] [PubMed] [Google Scholar]
  2. Cheverud J. M., Routman E. J., Duarte F. A., van Swinderen B., Cothran K., Perel C. Quantitative trait loci for murine growth. Genetics. 1996 Apr;142(4):1305–1319. doi: 10.1093/genetics/142.4.1305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Dietrich W. F., Miller J., Steen R., Merchant M. A., Damron-Boles D., Husain Z., Dredge R., Daly M. J., Ingalls K. A., O'Connor T. J. A comprehensive genetic map of the mouse genome. Nature. 1996 Mar 14;380(6570):149–152. doi: 10.1038/380149a0. [DOI] [PubMed] [Google Scholar]
  5. Dietrich W., Katz H., Lincoln S. E., Shin H. S., Friedman J., Dracopoli N. C., Lander E. S. A genetic map of the mouse suitable for typing intraspecific crosses. Genetics. 1992 Jun;131(2):423–447. doi: 10.1093/genetics/131.2.423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Grobet L., Martin L. J., Poncelet D., Pirottin D., Brouwers B., Riquet J., Schoeberlein A., Dunner S., Ménissier F., Massabanda J. A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle. Nat Genet. 1997 Sep;17(1):71–74. doi: 10.1038/ng0997-71. [DOI] [PubMed] [Google Scholar]
  7. Haley C. S., Knott S. A., Elsen J. M. Mapping quantitative trait loci in crosses between outbred lines using least squares. Genetics. 1994 Mar;136(3):1195–1207. doi: 10.1093/genetics/136.3.1195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Horvat S., Medrano J. F. Interval mapping of high growth (hg), a major locus that increases weight gain in mice. Genetics. 1995 Apr;139(4):1737–1748. doi: 10.1093/genetics/139.4.1737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Jansen R. C. Interval mapping of multiple quantitative trait loci. Genetics. 1993 Sep;135(1):205–211. doi: 10.1093/genetics/135.1.205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Keightley P. D., Bulfield G. Detection of quantitative trait loci from frequency changes of marker alleles under selection. Genet Res. 1993 Dec;62(3):195–203. doi: 10.1017/s0016672300031906. [DOI] [PubMed] [Google Scholar]
  11. Keightley P. D., Hardge T., May L., Bulfield G. A genetic map of quantitative trait loci for body weight in the mouse. Genetics. 1996 Jan;142(1):227–235. doi: 10.1093/genetics/142.1.227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kirkpatrick B. W., Mengelt A., Schulman N., Martin I. C. Identification of quantitative trait loci for prolificacy and growth in mice. Mamm Genome. 1998 Feb;9(2):97–102. doi: 10.1007/s003359900696. [DOI] [PubMed] [Google Scholar]
  13. Lander E. S., Green P. Construction of multilocus genetic linkage maps in humans. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2363–2367. doi: 10.1073/pnas.84.8.2363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lander E., Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet. 1995 Nov;11(3):241–247. doi: 10.1038/ng1195-241. [DOI] [PubMed] [Google Scholar]
  15. Lembertas A. V., Fisher J. S., Warden C. H., Wen P. Z., Xia Y. R., Lusis A. J. A locus on the X chromosome is linked to body length in mice. Mamm Genome. 1996 Mar;7(3):171–173. doi: 10.1007/s003359900048. [DOI] [PubMed] [Google Scholar]
  16. Lembertas A. V., Pérusse L., Chagnon Y. C., Fisler J. S., Warden C. H., Purcell-Huynh D. A., Dionne F. T., Gagnon J., Nadeau A., Lusis A. J. Identification of an obesity quantitative trait locus on mouse chromosome 2 and evidence of linkage to body fat and insulin on the human homologous region 20q. J Clin Invest. 1997 Sep 1;100(5):1240–1247. doi: 10.1172/JCI119637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. McPherron A. C., Lawler A. M., Lee S. J. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997 May 1;387(6628):83–90. doi: 10.1038/387083a0. [DOI] [PubMed] [Google Scholar]
  18. Nehls M., Lüno K., Schorpp M., Pfeifer D., Krause S., Matysiak-Scholze U., Dierbach H., Boehm T. YAC/P1 contigs defining the location of 56 microsatellite markers and several genes across a 3.4-cM interval on mouse chromosome 11. Mamm Genome. 1995 May;6(5):321–331. doi: 10.1007/BF00364794. [DOI] [PubMed] [Google Scholar]
  19. Pomp D., Oberbauer A. M., Murray J. D. Development of obesity following inactivation of a growth hormone transgene in mice. Transgenic Res. 1996 Jan;5(1):13–23. doi: 10.1007/BF01979918. [DOI] [PubMed] [Google Scholar]
  20. Pérusse L., Chagnon Y. C., Dionne F. T., Bouchard C. The human obesity gene map: the 1996 update. Obes Res. 1997 Jan;5(1):49–61. doi: 10.1002/j.1550-8528.1997.tb00283.x. [DOI] [PubMed] [Google Scholar]
  21. Riesner D., Steger G., Zimmat R., Owens R. A., Wagenhöfer M., Hillen W., Vollbach S., Henco K. Temperature-gradient gel electrophoresis of nucleic acids: analysis of conformational transitions, sequence variations, and protein-nucleic acid interactions. Electrophoresis. 1989 May-Jun;10(5-6):377–389. doi: 10.1002/elps.1150100516. [DOI] [PubMed] [Google Scholar]
  22. Warden C. H., Fisler J. S., Shoemaker S. M., Wen P. Z., Svenson K. L., Pace M. J., Lusis A. J. Identification of four chromosomal loci determining obesity in a multifactorial mouse model. J Clin Invest. 1995 Apr;95(4):1545–1552. doi: 10.1172/JCI117827. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. West D. B., Waguespack J., York B., Goudey-Lefevre J., Price R. A. Genetics of dietary obesity in AKR/J x SWR/J mice: segregation of the trait and identification of a linked locus on chromosome 4. Mamm Genome. 1994 Sep;5(9):546–552. doi: 10.1007/BF00354928. [DOI] [PubMed] [Google Scholar]
  24. York B., Lei K., West D. B. Sensitivity to dietary obesity linked to a locus on chromosome 15 in a CAST/Ei x C57BL/6J F2 intercross. Mamm Genome. 1996 Sep;7(9):677–681. doi: 10.1007/s003359900204. [DOI] [PubMed] [Google Scholar]
  25. Zeng Z. B. Theoretical basis for separation of multiple linked gene effects in mapping quantitative trait loci. Proc Natl Acad Sci U S A. 1993 Dec 1;90(23):10972–10976. doi: 10.1073/pnas.90.23.10972. [DOI] [PMC free article] [PubMed] [Google Scholar]

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