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PMID: 16462940 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Genetic and genomic analysis of a fat mass trait with complex inheritance reveals marked sex specificity.

PLoS genetics ·Vol. 2 ·No. 2 ·2006-02-00 ·Pages e15

Wang S, Yehya N, Schadt EE, Wang H, Drake TA, Lusis AJ

Abstract

The integration of expression profiling with linkage analysis has increasingly been used to identify genes underlying complex phenotypes. The effects of gender on the regulation of many physiological traits are well documented; however, "genetical genomic" analyses have not yet addressed the degree to which their conclusions are affected by sex. We constructed and densely genotyped a large F2 intercross derived from the inbred mouse strains C57BL/6J and C3H/HeJ on an apolipoprotein E null (ApoE-/-) background. This BXH.ApoE-/- population recapitulates several "metabolic syndrome" phenotypes. The cross consists of 334 animals of both sexes, allowing us to specifically test for the dependence of linkage on sex. We detected several thousand liver gene expression quantitative trait loci, a significant proportion of which are sex-biased. We used these analyses to dissect the genetics of gonadal fat mass, a complex trait with sex-specific regulation. We present evidence for a remarkably high degree of sex-dependence on both the cis and trans regulation of gene expression. We demonstrate how these analyses can be applied to the study of the genetics underlying gonadal fat mass, a complex trait showing significantly female-biased heritability. These data have implications on the potential effects of sex on the genetic regulation of other complex traits.

MeSH Terms
Adipose Tissue/physiology Animals Female Gene Expression Regulation Genotype Liver/metabolism Male Mice Mice, Inbred C3H Mice, Inbred C57BL Mice, Transgenic Phenotype Sex Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Wang Susanna
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Yehya Nadir
Schadt Eric E
Wang Hui
Drake Thomas A
Lusis Aldons J
Conflict of Interest

Competing interests. The authors have declared that no competing interests exist.

References (38)
38 references, click to expand
  1. Identification of quantitative trait loci influencing traits related to energy balance in selection and inbred lines of mice.
    Genetics. 1999 Jun;152(2):699-711 PMID: 10353911
  2. Highly multiplexed molecular inversion probe genotyping: over 10,000 targeted SNPs genotyped in a single tube assay.
    Genome Res. 2005 Feb;15(2):269-75 PMID: 15687290
  3. A sex-adjusted and age-adjusted genome screen for nested alcohol dependence diagnoses.
    Psychiatr Genet. 2005 Mar;15(1):25-30 PMID: 15722954
  4. Integrated transcriptional profiling and linkage analysis for identification of genes underlying disease.
    Nat Genet. 2005 Mar;37(3):243-53 PMID: 15711544
  5. Complex trait analysis of gene expression uncovers polygenic and pleiotropic networks that modulate nervous system function.
    Nat Genet. 2005 Mar;37(3):233-42 PMID: 15711545
  6. Uncovering regulatory pathways that affect hematopoietic stem cell function using 'genetical genomics'.
    Nat Genet. 2005 Mar;37(3):225-32 PMID: 15711547
  7. Cis-acting expression quantitative trait loci in mice.
    Genome Res. 2005 May;15(5):681-91 PMID: 15837804
  8. Genetic architecture of transcript-level variation in differentiating xylem of a eucalyptus hybrid.
    Genetics. 2005 Apr;169(4):2295-303 PMID: 15687266
  9. Methodological aspects of the genetic dissection of gene expression.
    Bioinformatics. 2005 May 15;21(10):2383-93 PMID: 15613385
  10. Bayesian model selection for genome-wide epistatic quantitative trait loci analysis.
    Genetics. 2005 Jul;170(3):1333-44 PMID: 15911579
  11. Signaling and circuitry of multiple MAPK pathways revealed by a matrix of global gene expression profiles.
    Science. 2000 Feb 4;287(5454):873-80 PMID: 10657304
  12. Functional discovery via a compendium of expression profiles.
    Cell. 2000 Jul 7;102(1):109-26 PMID: 10929718
  13. Analyzing high-density oligonucleotide gene expression array data.
    J Cell Biochem. 2000 Oct 20;80(2):192-202 PMID: 11074587
  14. Genetic contributions to body weight in mice: relationship of exploratory behavior to weight.
    Obes Res. 2003 Jul;11(7):828-38 PMID: 12855751
  15. Genetic loci for diet-induced atherosclerotic lesions and plasma lipids in mice.
    Mamm Genome. 2003 Jul;14(7):464-71 PMID: 12925895
  16. Trans-acting regulatory variation in Saccharomyces cerevisiae and the role of transcription factors.
    Nat Genet. 2003 Sep;35(1):57-64 PMID: 12897782
  17. Genetic factors in cardiovascular disease. 10 questions.
    Trends Cardiovasc Med. 2003 Nov;13(8):309-16 PMID: 14596945
  18. The nature and identification of quantitative trait loci: a community's view.
    Nat Rev Genet. 2003 Nov;4(11):911-6 PMID: 14634638
  19. The human obesity gene map: the 2003 update.
    Obes Res. 2004 Mar;12(3):369-439 PMID: 15044658
  20. Influence of sex and diet on quantitative trait loci for HDL cholesterol levels in an SM/J by NZB/BlNJ intercross population.
    J Lipid Res. 2004 May;45(5):881-8 PMID: 14993241
  21. An integrative genomics approach to the reconstruction of gene networks in segregating populations.
    Cytogenet Genome Res. 2004;105(2-4):363-74 PMID: 15237224
  22. Genetic analysis of genome-wide variation in human gene expression.
    Nature. 2004 Aug 12;430(7001):743-7 PMID: 15269782
  23. Coordinated genetic regulation of growth and lignin revealed by quantitative trait locus analysis of cDNA microarray data in an interspecific backcross of eucalyptus.
    Plant Physiol. 2004 Aug;135(4):2368-78 PMID: 15299141
  24. Sex- and lineage-specific inheritance of depression-like behavior in the rat.
    Mamm Genome. 2004 Aug;15(8):648-62 PMID: 15457344
  25. Evidence for sex-specific risk alleles in autism spectrum disorder.
    Am J Hum Genet. 2004 Dec;75(6):1117-23 PMID: 15467983
  26. Genetic inheritance of gene expression in human cell lines.
    Am J Hum Genet. 2004 Dec;75(6):1094-105 PMID: 15514893
  27. The Collaborative Cross, a community resource for the genetic analysis of complex traits.
    Nat Genet. 2004 Nov;36(11):1133-7 PMID: 15514660
  28. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results.
    Nat Genet. 1995 Nov;11(3):241-7 PMID: 7581446
  29. A genetic map of quantitative trait loci for body weight in the mouse.
    Genetics. 1996 Jan;142(1):227-35 PMID: 8770600
  30. Genetics of obesity in humans and animal models.
    Endocrinol Metab Clin North Am. 1996 Dec;25(4):801-13 PMID: 8977046
  31. Quantitative trait loci affecting body weight and fatness from a mouse line selected for extreme high growth.
    Genetics. 1998 Sep;150(1):369-81 PMID: 9725853
  32. Genetic loci determining bone density in mice with diet-induced atherosclerosis.
    Physiol Genomics. 2001 Apr 27;5(4):205-15 PMID: 11328966
  33. Genetical genomics: the added value from segregation.
    Trends Genet. 2001 Jul;17(7):388-91 PMID: 11418218
  34. Hormones, genetic factors, and gender differences in cardiovascular disease.
    Cardiovasc Res. 2002 Feb 15;53(3):550-7 PMID: 11861025
  35. Genetic dissection of transcriptional regulation in budding yeast.
    Science. 2002 Apr 26;296(5568):752-5 PMID: 11923494
  36. Combining mapping and arraying: An approach to candidate gene identification.
    Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):14903-6 PMID: 12415114
  37. Genetics of gene expression surveyed in maize, mouse and man.
    Nature. 2003 Mar 20;422(6929):297-302 PMID: 12646919
  38. Microarray standard data set and figures of merit for comparing data processing methods and experiment designs.
    Bioinformatics. 2003 May 22;19(8):956-65 PMID: 12761058
Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.0020015
Published
2006-02-00
Epub
2006-00-03
Pages
e15
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC1359071
Subset
IM
Grants
NICHD NIH HHS · T32 HD007228 · United States
NICHD NIH HHS · HD07228-24 · United States
NHLBI NIH HHS · P01 HL028481 · United States
NHLBI NIH HHS · HL-28481 · United States
NHLBI NIH HHS · P01 HL030568 · United States
NHLBI NIH HHS · HL-30568 · United States
External Links
PubMed source DOI: 10.1371/journal.pgen.0020015 PMC Full Text View journal details
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