Identifying Candidate Disease Gene GAD2 for Obesity by Computational Gene Prioritization Tool ENDEAVOUR

Identifying potential disease genes for complex disease is very important for understanding disease pathogenesis and providing preventive measures. The computational gene prioritization tools provide a promising and effective way for disease gene identification. Gene GAD2 on Chromosome 10p12 is a disputing candidate disease gene for obesity because of the contradictory conclusions obtained by association studies of different researchers. In this paper, a computational tool ENDEAVOUR is used to verify the probability of gene GAD2 being an obesity candidate disease gene. ENDEAVOUR evaluates each candidate gene based on its similarity with the training genes (known disease genes). The high prioritization of gene GAD2 in the computational results means that the gene GAD2 has high probability to be a disease gene for obesity.

[1]  C. Bouchard,et al.  FTO: the first gene contributing to common forms of human obesity , 2008, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[2]  C. Bouchard,et al.  GAD2 gene sequence variations are associated with eating behaviors and weight gain in women from the Quebec family study , 2009, Physiology & Behavior.

[3]  Gert Vriend,et al.  GeneSeeker: extraction and integration of human disease-related information from web-based genetic databases , 2005, Nucleic Acids Res..

[4]  Vassilis Aidinis,et al.  Comparative expression profiling in pulmonary fibrosis suggests a role of hypoxia-inducible factor-1alpha in disease pathogenesis. , 2007, American journal of respiratory and critical care medicine.

[5]  R. Myers,et al.  Candidate-gene approaches for studying complex genetic traits: practical considerations , 2002, Nature Reviews Genetics.

[6]  M. McCarthy,et al.  Significant Linkage of BMI to Chromosome 10p in the U.K. Population and Evaluation of GAD2 as a Positional Candidate , 2006, Diabetes.

[7]  J C Murray,et al.  Identification of novel candidate genes associated with cleft lip and palate using array comparative genomic hybridisation , 2007, Journal of Medical Genetics.

[8]  P. Kopelman.  Obesity as a medical problem , 2000, Nature.

[9]  Bart De Moor,et al.  Endeavour update: a web resource for gene prioritization in multiple species , 2008, Nucleic Acids Res..

[10]  Frances S. Turner,et al.  Computational disease gene identification: a concert of methods prioritizes type 2 diabetes and obesity candidate genes , 2006, Nucleic acids research.

[11]  David J. Porteous,et al.  SUSPECTS : enabling fast and effective prioritization of positional candidates , 2005 .

[12]  P. Boutin,et al.  GAD2: a polygenic contribution to genetic susceptibility for common obesity? , 2005, Pathologie-biologie.

[13]  Bassem A. Hassan,et al.  Gene prioritization through genomic data fusion , 2006, Nature Biotechnology.

[14]  D. Allison,et al.  Is GAD2 on chromosome 10p12 a potential candidate gene for morbid obesity? , 2005, Nutrition reviews.

[15]  J. Hebebrand,et al.  Genome scan for childhood and adolescent obesity in German families. , 2003, Pediatrics.

[16]  P. Bork,et al.  G2D: a tool for mining genes associated with disease , 2005, BMC Genetics.

[17]  David J. Porteous,et al.  Speeding disease gene discovery by sequence based candidate prioritization , 2005, BMC Bioinformatics.

[18]  K. Clément,et al.  GAD2 on Chromosome 10p12 Is a Candidate Gene for Human Obesity , 2003, PLoS biology.

[19]  P. Froguel,et al.  The genetics of human obesity , 2005, Nature Reviews Genetics.

[20]  I. Libman,et al.  Association of the -243 A-->G polymorphism of the glutamate decarboxylase 2 gene with obesity in girls with premature pubarche. , 2009, Fertility and sterility.

[21]  J. Hebebrand,et al.  Independent confirmation of a major locus for obesity on chromosome 10. , 2000, The Journal of clinical endocrinology and metabolism.

[22]  Luca Benini,et al.  TOM: a web-based integrated approach for identification of candidate disease genes , 2006, Nucleic Acids Res..

[23]  Frances S. Turner,et al.  POCUS: mining genomic sequence annotation to predict disease genes , 2003, Genome Biology.

[24]  Francesco Pinciroli,et al.  GFINDer: genetic disease and phenotype location statistical analysis and mining of dynamically annotated gene lists , 2005, Nucleic Acids Res..

[25]  P. Boutin,et al.  Is glutamate decarboxylase 2 (GAD2) a genetic link between low birth weight and subsequent development of obesity in children? , 2005, The Journal of clinical endocrinology and metabolism.

[26]  Cisca Wijmenga,et al.  A strategy to search for common obesity and type 2 diabetes genes , 2007, Trends in Endocrinology & Metabolism.

[27]  S. Hunt,et al.  Lack of Association of Glutamate Decarboxylase 2 Gene Polymorphisms with Severe Obesity in Utah , 2006, Obesity.

[28]  P. Robinson,et al.  Walking the interactome for prioritization of candidate disease genes. , 2008, American journal of human genetics.

[29]  J. Nadeau,et al.  Finding Genes That Underlie Complex Traits , 2002, Science.

[30]  L. Cardon,et al.  Association study designs for complex diseases , 2001, Nature Reviews Genetics.

[31]  C. Vaisse,et al.  Emerging trends in the search for genetic variants predisposing to human obesity , 2003, Current opinion in clinical nutrition and metabolic care.

[32]  P. Kwok,et al.  Lack of Support for the Association between GAD2 Polymorphisms and Severe Human Obesity , 2005, PLoS biology.

[33]  Alan F. Scott,et al.  Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders , 2004, Nucleic Acids Res..