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Title: Medical Sequencing at the extremes of Human Body Mass

Abstract

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.

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Director. Office of Science. Biological andEnvironmental Research
OSTI Identifier:
918660
Report Number(s):
LBNL-61611
R&D Project: 626809; BnR: KP1103010; TRN: US200819%%384
DOE Contract Number:  
DE-AC02-05CH11231
Resource Type:
Journal Article
Journal Name:
American Journal of Nature Genetics
Additional Journal Information:
Journal Volume: 80; Journal Issue: 4; Related Information: Journal Publication Date: 04/2007
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; EXONS; GENES; GENETICS; METABOLIC DISEASES; MICE; PHENOTYPE; SEGREGATION

Citation Formats

Ahituv, Nadav, Kavaslar, Nihan, Schackwitz, Wendy, Ustaszewski, Anna, Martin, Joes, Hebert, Sybil, Doelle, Heather, Ersoy, Baran, Kryukov, Gregory, Schmidt, Steffen, Yosef, Nir, Ruppin, Eytan, Sharan, Roded, Vaisse, Christian, Sunyaev, Shamil, Dent, Robert, Cohen, Jonathan, McPherson, Ruth, and Pennacchio, Len A. Medical Sequencing at the extremes of Human Body Mass. United States: N. p., 2006. Web.
Ahituv, Nadav, Kavaslar, Nihan, Schackwitz, Wendy, Ustaszewski, Anna, Martin, Joes, Hebert, Sybil, Doelle, Heather, Ersoy, Baran, Kryukov, Gregory, Schmidt, Steffen, Yosef, Nir, Ruppin, Eytan, Sharan, Roded, Vaisse, Christian, Sunyaev, Shamil, Dent, Robert, Cohen, Jonathan, McPherson, Ruth, & Pennacchio, Len A. Medical Sequencing at the extremes of Human Body Mass. United States.
Ahituv, Nadav, Kavaslar, Nihan, Schackwitz, Wendy, Ustaszewski, Anna, Martin, Joes, Hebert, Sybil, Doelle, Heather, Ersoy, Baran, Kryukov, Gregory, Schmidt, Steffen, Yosef, Nir, Ruppin, Eytan, Sharan, Roded, Vaisse, Christian, Sunyaev, Shamil, Dent, Robert, Cohen, Jonathan, McPherson, Ruth, and Pennacchio, Len A. 2006. "Medical Sequencing at the extremes of Human Body Mass". United States. https://www.osti.gov/servlets/purl/918660.
@article{osti_918660,
title = {Medical Sequencing at the extremes of Human Body Mass},
author = {Ahituv, Nadav and Kavaslar, Nihan and Schackwitz, Wendy and Ustaszewski, Anna and Martin, Joes and Hebert, Sybil and Doelle, Heather and Ersoy, Baran and Kryukov, Gregory and Schmidt, Steffen and Yosef, Nir and Ruppin, Eytan and Sharan, Roded and Vaisse, Christian and Sunyaev, Shamil and Dent, Robert and Cohen, Jonathan and McPherson, Ruth and Pennacchio, Len A},
abstractNote = {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.},
doi = {},
url = {https://www.osti.gov/biblio/918660}, journal = {American Journal of Nature Genetics},
number = 4,
volume = 80,
place = {United States},
year = {Fri Sep 01 00:00:00 EDT 2006},
month = {Fri Sep 01 00:00:00 EDT 2006}
}