Skip Navigation



Human Molecular Genetics Advance Access published online on August 7, 2006
Human Molecular Genetics, doi:10.1093/hmg/ddl204
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrowOA All Versions of this Article:
15/18/2709    most recent
ddl204v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Stone, S.
Right arrow Articles by Shattuck, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stone, S.
Right arrow Articles by Shattuck, D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received June 8, 2006
Revised July 28, 2006
Accepted July 28, 2006

Article

TBC1D1 is a candidate for a severe obesity gene and evidence for a gene/gene interaction in obesity predisposition

Steven Stone 1 *, Victor Abkevich 2, Deanna L. Russell 2, Robyn Riley 2, Kirsten Timms 2, Thanh Tran 2, Deborah Trem 2, David Frank 2, Srikanth Jammulapati 2, Chris D. Neff 2, Diana Iliev 2, Richard Gress 3, Gongping He 2, Georges C. Frech 2, Ted D. Adams 3, Mark H. Skolnick 2, Jerry S. Lanchbury 2, Alexander Gutin 2, Steven C. Hunt 3, and Donna Shattuck 2

1 Myriad Genetics, Inc., 320 Wakara Way, Salt Lake City, UT, 84108, USA
2 Myriad Genetics, Inc., Salt Lake City, UT, 84108, USA
3 Cardiovascular Genetics, Department of Medicine, University of Utah, Salt Lake City UT., 84108, USA

* To whom correspondence should be addressed.
Steven Stone, E-mail: sstone{at}myriad.com


  Abstract

The molecular etiology of obesity predisposition is largely unknown. Here, we present evidence that genetic variation in TBC1D1 confers risk for severe obesity in females. We identified a coding variant (R125W) in TBC1D1 that segregated with the disease in 4p15-14-linked obesity pedigrees. In cases derived from pedigrees with the strongest linkage evidence, the variant was significantly associated with obesity (p-value of 0.000007), and chromosomes carrying R125W accounted for the majority of the evidence that originally linked 4p15-14 with the disease. In addition, by selecting families that segregated R125W with obesity, we were able to generate highly significant linkage evidence for an obesity predisposition locus at 4q34-35. This result provides additional and confirming evidence that R125W affects obesity susceptibility, delimits the location of an obesity gene at 4q34-35, and identifies a gene/gene interaction that influences the risk for obesity predisposition. Finally, although the function of TBC1D1 is unknown, the protein is structurally similar to a known regulator of insulin-mediated Glut4 translocation.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
G. R. Peck, J. A. Chavez, W. G. Roach, B. A. Budnik, W. S. Lane, H. K. R. Karlsson, J. R. Zierath, and G. E. Lienhard
Insulin-stimulated Phosphorylation of the Rab GTPase-activating Protein TBC1D1 Regulates GLUT4 Translocation
J. Biol. Chem., October 30, 2009; 284(44): 30016 - 30023.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
S. E Leney and J. M Tavare
The molecular basis of insulin-stimulated glucose uptake: signalling, trafficking and potential drug targets
J. Endocrinol., October 1, 2009; 203(1): 1 - 18.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
C. Pehmoller, J. T. Treebak, J. B. Birk, S. Chen, C. MacKintosh, D. G. Hardie, E. A. Richter, and J. F. P. Wojtaszewski
Genetic disruption of AMPK signaling abolishes both contraction- and insulin-stimulated TBC1D1 phosphorylation and 14-3-3 binding in mouse skeletal muscle
Am J Physiol Endocrinol Metab, September 1, 2009; 297(3): E665 - E675.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
J.J. Ireland, A.E. Zielak-Steciwko, F. Jimenez-Krassel, J. Folger, A. Bettegowda, D. Scheetz, S. Walsh, F. Mossa, P.G. Knight, G.W. Smith, et al.
Variation in the Ovarian Reserve Is Linked to Alterations in Intrafollicular Estradiol Production and Ovarian Biomarkers of Follicular Differentiation and Oocyte Quality in Cattle
Biol Reprod, May 1, 2009; 80(5): 954 - 964.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
K. Sakamoto and G. D. Holman
Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic
Am J Physiol Endocrinol Metab, July 1, 2008; 295(1): E29 - E37.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
D. Meyre, M. Farge, C. Lecoeur, C. Proenca, E. Durand, F. Allegaert, J. Tichet, M. Marre, B. Balkau, J. Weill, et al.
R125W coding variant in TBC1D1 confers risk for familial obesity and contributes to linkage on chromosome 4p14 in the French population
Hum. Mol. Genet., June 15, 2008; 17(12): 1798 - 1802.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. B. Taylor, D. An, H. F. Kramer, H. Yu, N. L. Fujii, K. S. C. Roeckl, N. Bowles, M. F. Hirshman, J. Xie, E. P. Feener, et al.
Discovery of TBC1D1 as an Insulin-, AICAR-, and Contraction-stimulated Signaling Nexus in Mouse Skeletal Muscle
J. Biol. Chem., April 11, 2008; 283(15): 9787 - 9796.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
A. C. Roman, D. A. Benitez, J. M. Carvajal-Gonzalez, and P. M. Fernandez-Salguero
Genome-wide B1 retrotransposon binds the transcription factors dioxin receptor and Slug and regulates gene expression in vivo
PNAS, February 5, 2008; 105(5): 1632 - 1637.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
G. I. Welsh, S. E. Leney, B. Lloyd-Lewis, M. Wherlock, A. J. Lindsay, M. W. McCaffrey, and J. M. Tavare
Rip11 is a Rab11- and AS160-RabGAP-binding protein required for insulin-stimulated glucose uptake in adipocytes
J. Cell Sci., December 1, 2007; 120(23): 4197 - 4208.
[Abstract] [Full Text] [PDF]

Home page
 Epidemiol RevHome page
W. Yang, T. Kelly, and J. He
Genetic Epidemiology of Obesity
Epidemiol. Rev., June 12, 2007; (2007) mxm004v1.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
J. S Fisler and C. H Warden
The current and future search for obesity genes
Am. J. Clinical Nutrition, January 1, 2007; 85(1): 1 - 2.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.