Medical Sequencing at the extremes of Human Body Mass
Body weight is a quantitative trait with significantheritability in humans. To identify potential genetic contributors tothis phenotype, we resequenced the coding exons and splice junctions of58 genes in 379 obese and 378 lean individuals. Our 96Mb survey included21 genes associated with monogenic forms of obesity in humans or mice, aswell as 37 genes that function in body weight-related pathways. We foundthat the monogenic obesity-associated gene group was enriched for rarenonsynonymous variants unique to the obese (n=46) versus lean (n=26)populations. Computational analysis further predicted a significantlygreater fraction of deleterious variants within the obese cohort.Consistent with the complex inheritance of body weight, we did notobserve obvious familial segregation in the majority of the 28 availablekindreds. Taken together, these data suggest that multiple rare alleleswith variable penetrance contribute to obesity in the population andprovide a deep medical sequencing based approach to detectthem.
- Research Organization:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Organization:
- USDOE Director. Office of Science. Biological andEnvironmental Research
- DOE Contract Number:
- DE-AC02-05CH11231
- OSTI ID:
- 918660
- Report Number(s):
- LBNL-61611; R&D Project: 626809; BnR: KP1103010; TRN: US200819%%384
- Journal Information:
- American Journal of Nature Genetics, Vol. 80, Issue 4; Related Information: Journal Publication Date: 04/2007
- Country of Publication:
- United States
- Language:
- English
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