TBC1D1 is a candidate for a severe obesity gene and evidence for a gene/gene interaction in obesity predisposition
| Autor: | Georges C. Frech, Deborah Trem, Ted D. Adams, David A. Frank, Victor Abkevich, Kirsten Timms, Gongping He, Robyn Riley, Srikanth Jammulapati, Steven C. Hunt, Donna Shattuck, Deanna L. Russell, Jerry S. Lanchbury, Richard E. Gress, Mark H. Skolnick, Chris Neff, Thanh Tran, Diana Iliev, Alexander Gutin, Steven Stone |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Gene Expression Locus (genetics) Pedigree chart Disease Biology Polymorphism Single Nucleotide Linkage Disequilibrium Gene interaction Proto-Oncogene Proteins Endopeptidases Genetic variation Genetics medicine Humans Tissue Distribution Obesity RNA Messenger Molecular Biology Gene Genetics (clinical) Oncogene Proteins Genetic Variation TBC1D1 General Medicine medicine.disease Pedigree Phenotype Haplotypes Female Chromosomes Human Pair 4 Lod Score Ubiquitin Thiolesterase |
| Zdroj: | Human Molecular Genetics. 15:2709-2720 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddl204 |
| Popis: | 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 = 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. |
| Databáze: | OpenAIRE |
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