Abstract
Obesity is a complex trait, determined by many genes and influenced by environmental factors. Mapping genomic loci contributing to obesity helps to identify gene variants responsible for differences in the phenotype. However, measuring fat content alone is often not sufficient to identify the underlying gene or genes. Besides in-depth phenotyping, well-designed genetic populations and the combined analysis of data of different origins are necessary to detect one of several genetic determinants. Structured mouse populations and linking information from different experiments help to simplify the complexity in the search for direct genetic effects or factors that are hidden in the genome. In this chapter we present an example of how the physicochemical characterization of adipose tissue in BXD recombinant inbred lines contributes to enlighten the obese phenotype of mice. We describe the search for gene(s) contributing to collagen content in adipose tissue of BXD strains using the GeneNetwork platform.
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References
Chadt A, Leicht K, Deshmukh A, Jiang LQ, Scherneck S, Bernhardt U, Dreja T, Vogel H, Schmolz K, Kluge R, Zierath JR, Hultschig C, Hoeben RC, Schurmann A, Joost HG, Al-Hasani H (2008) Tbc1d1 mutation in lean mouse strain confers leanness and protects from diet-induced obesity. Nat Genet 40(11):1354–1359. doi:10.1038/ng.244
Crabbe JC, Belknap JK (1993) Behavior genetic analyses of drug withdrawal. Alcohol Alcohol Suppl 2:477–482
Taylor BA, Rowe L (1984) Genes for serum amyloid A proteins map to chromosome 7 in the mouse. Mol Gen Genet 195(3):491–499
Groves MG, Rosenstreich DL, Taylor BA, Osterman JV (1980) Host defenses in experimental scrub typhus: mapping the gene that controls natural resistance in mice. J Immunol 125(3):1395–1399
Peirce JL, Lu L, Gu J, Silver LM, Williams RW (2004) A new set of BXD recombinant inbred lines from advanced intercross populations in mice. BMC Genet 5:7. doi:10.1186/1471-2156-5-7
Churchill GA, Airey DC, Allayee H, Angel JM, Attie AD, Beatty J, Beavis WD, Belknap JK, Bennett B, Berrettini W, Bleich A, Bogue M, Broman KW, Buck KJ, Buckler E, Burmeister M, Chesler EJ, Cheverud JM, Clapcote S, Cook MN, Cox RD, Crabbe JC, Crusio WE, Darvasi A, Deschepper CF, Doerge RW, Farber CR, Forejt J, Gaile D, Garlow SJ, Geiger H, Gershenfeld H, Gordon T, Gu J, Gu W, de Haan G, Hayes NL, Heller C, Himmelbauer H, Hitzemann R, Hunter K, Hsu HC, Iraqi FA, Ivandic B, Jacob HJ, Jansen RC, Jepsen KJ, Johnson DK, Johnson TE, Kempermann G, Kendziorski C, Kotb M, Kooy RF, Llamas B, Lammert F, Lassalle JM, Lowenstein PR, Lu L, Lusis A, Manly KF, Marcucio R, Matthews D, Medrano JF, Miller DR, Mittleman G, Mock BA, Mogil JS, Montagutelli X, Morahan G, Morris DG, Mott R, Nadeau JH, Nagase H, Nowakowski RS, O'Hara BF, Osadchuk AV, Page GP, Paigen B, Paigen K, Palmer AA, Pan HJ, Peltonen-Palotie L, Peirce J, Pomp D, Pravenec M, Prows DR, Qi Z, Reeves RH, Roder J, Rosen GD, Schadt EE, Schalkwyk LC, Seltzer Z, Shimomura K, Shou S, Sillanpaa MJ, Siracusa LD, Snoeck HW, Spearow JL, Svenson K, Tarantino LM, Threadgill D, Toth LA, Valdar W, de Villena FP, Warden C, Whatley S, Williams RW, Wiltshire T, Yi N, Zhang D, Zhang M, Zou F, Complex Trait C (2004) The Collaborative Cross, a community resource for the genetic analysis of complex traits. Nat Genet 36(11):1133–1137. doi:10.1038/ng1104-1133
Threadgill DW, Miller DR, Churchill GA, de Villena FP (2011) The collaborative cross: a recombinant inbred mouse population for the systems genetic era. ILAR J 52(1):24–31
Svenson KL, Gatti DM, Valdar W, Welsh CE, Cheng R, Chesler EJ, Palmer AA, McMillan L, Churchill GA (2012) High-resolution genetic mapping using the mouse diversity outbred population. Genetics 190(2):437–447. doi:10.1534/genetics.111.132597
Dogan A, Lasch P, Neuschl C, Millrose MK, Alberts R, Schughart K, Naumann D, Brockmann GA (2013) ATR-FTIR spectroscopy reveals genomic loci regulating the tissue response in high fat diet fed BXD recombinant inbred mouse strains. BMC Genomics 14:386. doi:10.1186/1471-2164-14-386, 1471-2164-14-386 [pii]
Sen I, Bozkurt O, Aras E, Heise S, Brockmann GA, Severcan F (2015) Lipid profiles of adipose and muscle tissues in mouse models of juvenile onset of obesity without high fat diet induction: a fourier transform infrared (FT-IR) spectroscopic study. Appl Spectrosc 69(6):679–688. doi:10.1366/14-07443
Yang H, Ding Y, Hutchins LN, Szatkiewicz J, Bell TA, Paigen BJ, Graber JH, de Villena FP, Churchill GA (2009) A customized and versatile high-density genotyping array for the mouse. Nat Methods 6(9):663–666, doi:nmeth.1359 [pii]10.1038/nmeth.1359
Wu C, Delano DL, Mitro N, Su SV, Janes J, McClurg P, Batalov S, Welch GL, Zhang J, Orth AP, Walker JR, Glynne RJ, Cooke MP, Takahashi JS, Shimomura K, Kohsaka A, Bass J, Saez E, Wiltshire T, Su AI (2008) Gene set enrichment in eQTL data identifies novel annotations and pathway regulators. PLoS Genet 4(5), e1000070. doi:10.1371/journal.pgen.1000070
Chin KC, Cresswell P (2001) Viperin (cig5), an IFN-inducible antiviral protein directly induced by human cytomegalovirus. Proc Natl Acad Sci U S A 98(26):15125–15130. doi:10.1073/pnas.011593298
Hinson ER, Cresswell P (2009) The N-terminal amphipathic alpha-helix of viperin mediates localization to the cytosolic face of the endoplasmic reticulum and inhibits protein secretion. J Biol Chem 284(7):4705–4712. doi:10.1074/jbc.M807261200
Wang X, Hinson ER, Cresswell P (2007) The interferon-inducible protein viperin inhibits influenza virus release by perturbing lipid rafts. Cell Host Microbe 2(2):96–105. doi:10.1016/j.chom.2007.06.009
Lu L, Wei L, Peirce JL, Wang X, Zhou J, Homayouni R, Williams RW, Airey DC (2008) Using gene expression databases for classical trait QTL candidate gene discovery in the BXD recombinant inbred genetic reference population: mouse forebrain weight. BMC Genomics 9:444. doi:10.1186/1471-2164-9-444
Gatti D, Maki A, Chesler EJ, Kirova R, Kosyk O, Lu L, Manly KF, Williams RW, Perkins A, Langston MA, Threadgill DW, Rusyn I (2007) Genome-level analysis of genetic regulation of liver gene expression networks. Hepatology 46(2):548–557. doi:10.1002/hep.21682
Acknowledgements
We acknowledge permanent support by the German Research Foundation (DFG), the German Ministry of Education and Research (BMBF), the GeNeSys Network and the COST action SYSGENET BM 0901.
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Brockmann, G.A., Arends, D., Heise, S., Dogan, A. (2017). Systems Genetics of Obesity. In: Schughart, K., Williams, R. (eds) Systems Genetics. Methods in Molecular Biology, vol 1488. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6427-7_23
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DOI: https://doi.org/10.1007/978-1-4939-6427-7_23
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