Genomic Analysis of Metabolic Pathway Gene Expression in Mice

Overview

Journal Genome Biol

Specialties Biology
Genetics

Date 2005 Jul 7

PMID 15998448

Citations 41

Authors

Anatole Ghazalpour

Sudheer Doss

Sonal S Sheth

Leslie A Ingram-Drake

Eric E Schadt

Aldons J Lusis

Thomas A Drake

Affiliations

Soon will be listed here.

Abstract

Background: A segregating population of (C57BL/6J x DBA/2J)F2 intercross mice was studied for obesity-related traits and for global gene expression in liver. Quantitative trait locus analyses were applied to the subcutaneous fat-mass trait and all gene-expression data. These data were then used to identify gene sets that are differentially perturbed in lean and obese mice.

Results: We integrated global gene-expression data with phenotypic and genetic segregation analyses to evaluate metabolic pathways associated with obesity. Using two approaches we identified 13 metabolic pathways whose genes are coordinately regulated in association with obesity. Four genomic regions on chromosomes 3, 6, 16, and 19 were found to control the coordinated expression of these pathways. Using criteria that included trait correlation, differential gene expression, and linkage to genomic regions, we identified novel genes potentially associated with the identified pathways.

Conclusion: This study demonstrates that genetic and gene-expression data can be integrated to identify pathways associated with clinical traits and their underlying genetic determinants.

Citing Articles

Hub gene identification and immune infiltration analysis in hepatocellular carcinoma: Computational approach.

Pulakuntla S, Singh S, Reddy V In Silico Pharmacol. 2024; 12(1):39.

PMID: 38721057 PMC: 11074094. DOI: 10.1007/s40203-024-00215-2.

Applying network and genetic analysis to the potato metabolome.

Levina A, Hoekenga O, Gordin M, Broeckling C, De Jong W Front Plant Sci. 2023; 14:1108351.

PMID: 37152172 PMC: 10154602. DOI: 10.3389/fpls.2023.1108351.

Unraveling the role of salt-sensitivity genes in obesity with integrated network biology and co-expression analysis.

Sabir J, El Omri A, Banaganapalli B, Aljuaid N, Shaikh Omar A, Altaf A PLoS One. 2020; 15(2):e0228400.

PMID: 32027667 PMC: 7004317. DOI: 10.1371/journal.pone.0228400.

Dissecting the Role of NF-κb Protein Family and Its Regulators in Rheumatoid Arthritis Using Weighted Gene Co-Expression Network.

Sabir J, El Omri A, Banaganapalli B, Al-Shaeri M, Alkenani N, Sabir M Front Genet. 2019; 10:1163.

PMID: 31824568 PMC: 6879671. DOI: 10.3389/fgene.2019.01163.

An integrative systems genetics approach reveals potential causal genes and pathways related to obesity.

Kogelman L, Zhernakova D, Westra H, Cirera S, Fredholm M, Franke L Genome Med. 2015; 7:105.

PMID: 26482556 PMC: 4617184. DOI: 10.1186/s13073-015-0229-0.

References

Lee D, Seung H . Learning the parts of objects by non-negative matrix factorization. Nature. 1999; 401(6755):788-91. DOI: 10.1038/44565. View

Doss S, Schadt E, Drake T, Lusis A . Cis-acting expression quantitative trait loci in mice. Genome Res. 2005; 15(5):681-91. PMC: 1088296. DOI: 10.1101/gr.3216905. View

Drake T, Schadt E, Hannani K, Kabo J, Krass K, Colinayo V . Genetic loci determining bone density in mice with diet-induced atherosclerosis. Physiol Genomics. 2001; 5(4):205-15. DOI: 10.1152/physiolgenomics.2001.5.4.205. View

Manly K, Cudmore Jr R, Meer J . Map Manager QTX, cross-platform software for genetic mapping. Mamm Genome. 2001; 12(12):930-2. DOI: 10.1007/s00335-001-1016-3. View

Stoll M, Cowley Jr A, Tonellato P, Greene A, Kaldunski M, Roman R . A genomic-systems biology map for cardiovascular function. Science. 2001; 294(5547):1723-6. DOI: 10.1126/science.1062117. View

Kanehisa M, Goto S, Kawashima S, Nakaya A . The KEGG databases at GenomeNet. Nucleic Acids Res. 2001; 30(1):42-6. PMC: 99091. DOI: 10.1093/nar/30.1.42. View

Klose J, Nock C, Herrmann M, Stuhler K, Marcus K, Bluggel M . Genetic analysis of the mouse brain proteome. Nat Genet. 2002; 30(4):385-93. DOI: 10.1038/ng861. View

Su A, Cooke M, Ching K, Hakak Y, Walker J, Wiltshire T . Large-scale analysis of the human and mouse transcriptomes. Proc Natl Acad Sci U S A. 2002; 99(7):4465-70. PMC: 123671. DOI: 10.1073/pnas.012025199. View

Brem R, Yvert G, Clinton R, Kruglyak L . Genetic dissection of transcriptional regulation in budding yeast. Science. 2002; 296(5568):752-5. DOI: 10.1126/science.1069516. View

10.

Wayne M, McIntyre L . Combining mapping and arraying: An approach to candidate gene identification. Proc Natl Acad Sci U S A. 2002; 99(23):14903-6. PMC: 137517. DOI: 10.1073/pnas.222549199. View

11.

Kitano H . Computational systems biology. Nature. 2002; 420(6912):206-10. DOI: 10.1038/nature01254. View

12.

Diehn M, Sherlock G, Binkley G, Jin H, Matese J, Hernandez-Boussard T . SOURCE: a unified genomic resource of functional annotations, ontologies, and gene expression data. Nucleic Acids Res. 2003; 31(1):219-23. PMC: 165461. DOI: 10.1093/nar/gkg014. View

13.

Jansen R . Studying complex biological systems using multifactorial perturbation. Nat Rev Genet. 2003; 4(2):145-51. DOI: 10.1038/nrg996. View

14.

Schadt E, Monks S, Drake T, Lusis A, Che N, Colinayo V . Genetics of gene expression surveyed in maize, mouse and man. Nature. 2003; 422(6929):297-302. DOI: 10.1038/nature01434. View

15.

Dennis Jr G, Sherman B, Hosack D, Yang J, Gao W, Lane H . DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol. 2003; 4(5):P3. View

16.

He Y, Dai H, Schadt E, Cavet G, Edwards S, Stepaniants S . Microarray standard data set and figures of merit for comparing data processing methods and experiment designs. Bioinformatics. 2003; 19(8):956-65. DOI: 10.1093/bioinformatics/btg126. View

17.

Mootha V, Lindgren C, Eriksson K, Subramanian A, Sihag S, Lehar J . PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet. 2003; 34(3):267-73. DOI: 10.1038/ng1180. View

18.

Colinayo V, Qiao J, Wang X, Krass K, Schadt E, Lusis A . Genetic loci for diet-induced atherosclerotic lesions and plasma lipids in mice. Mamm Genome. 2003; 14(7):464-71. DOI: 10.1007/s00335-002-2187-2. View

19.

Lan H, Stoehr J, Nadler S, Schueler K, Yandell B, Attie A . Dimension reduction for mapping mRNA abundance as quantitative traits. Genetics. 2003; 164(4):1607-14. PMC: 1462655. DOI: 10.1093/genetics/164.4.1607. View

20.

Nadeau J, Burrage L, Restivo J, Pao Y, Churchill G, Hoit B . Pleiotropy, homeostasis, and functional networks based on assays of cardiovascular traits in genetically randomized populations. Genome Res. 2003; 13(9):2082-91. PMC: 403692. DOI: 10.1101/gr.1186603. View