| | |  | | | | Record from Web of Science® | | | | | | |
| PGC-1 alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes |
|
|
| Author(s): Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstrale M, Laurila E, Houstis N, Daly MJ, Patterson N, Mesirov JP, Golub TR, Tamayo P, Spiegelman B, Lander ES, Hirschhorn JN, Altshuler D, Groop LC |
| Source: NATURE GENETICS Volume: 34 Issue: 3 Pages: 267-273 Published: JUL 2003 |
| Times Cited: 989 References: 33 |
| Abstract: DNA microarrays can be used to identify gene expression changes characteristic of human disease. This is challenging, however, when relevant differences are subtle at the level of individual genes. We introduce an analytical strategy, Gene Set Enrichment Analysis, designed to detect modest but coordinate changes in the expression of groups of functionally related genes. Using this approach, we identify a set of genes involved in oxidative phosphorylation whose expression is coordinately decreased in human diabetic muscle. Expression of these genes is high at sites of insulin-mediated glucose disposal, activated by PGC-1alpha and correlated with total-body aerobic capacity. Our results associate this gene set with clinically important variation in human metabolism and illustrate the value of pathway relationships in the analysis of genomic profiling experiments. |
| Document Type: Article |
| Language: English |
| Reprint Address: Altshuler, D (reprint author), MIT, Whitehead Inst, Ctr Genome Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA |
Addresses:
1. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA 02139 USA
2. Harvard Med Sch, Dept Med, Boston, MA USA
3. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
4. Lund Univ, Dept Endocrinol, Wallenberg Lab, Univ Hosp MAS, S-20502 Malmo, Sweden
5. Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA
6. MIT, Dept Biol, Cambridge, MA USA
7. Harvard Med Sch, Dept Genet, Boston, MA USA
8. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA
9. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA
10. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
11. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA |
| Publisher: NATURE PUBLISHING GROUP, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Genetics & Heredity |
| IDS Number: 695DF |
| ISSN: 1061-4036 |
| DOI: 10.1038/ng1180 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |