title: Gene-specific function prediction for non-synonymous mutations in monogenic diabetes genes.
abstract: The rapid progress of genomic technologies has been providing new opportunities to address the need of maturity-onset diabetes of the young (MODY) molecular diagnosis. However, whether a new mutation causes MODY can be questionable. A number of in silico methods have been developed to predict functional effects of rare human mutations. The purpose of this study is to compare the performance of different bioinformatics methods in the functional prediction of nonsynonymous mutations in each MODY gene, and provides reference matrices to assist the molecular diagnosis of MODY. Our study showed that the prediction scores by different methods of the diabetes mutations were highly correlated, but were more complimentary than replacement to each other. The available in silico methods for the prediction of diabetes mutations had varied performances across different genes. Applying gene-specific thresholds defined by this study may be able to increase the performance of in silico prediction of disease-causing mutations.
authors.affiliation: Endocrine Genetics Lab, The McGill University Health Center (Montreal Children's Hospital), Montréal, Québec, Canada.
authors.forename: Quan
authors.initials: Q
authors.lastname: Li
authors.affiliation: Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas School of Public Health, Houston, Texas, United States of America.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States of America; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.affiliation: Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas School of Public Health, Houston, Texas, United States of America; Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: Endocrine Genetics Lab, The McGill University Health Center (Montreal Children's Hospital), Montréal, Québec, Canada.
authors.forename: Constantin
authors.initials: C
authors.lastname: Polychronakos
authors.affiliation: Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas School of Public Health, Houston, Texas, United States of America.
authors.forename: Hui-Qi
authors.initials: HQ
authors.lastname: Qu
mesh_terms: D000293:Adolescent; D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D002648:Child; D019295:Computational Biology / Q000379:methods / Q000706:statistics & numerical data*; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D008049:Lipase / Q000235:genetics; D020125:Mutation, Missense; D051761:Paired Box Transcription Factors / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D064233:Sulfonylurea Receptors / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics; D055815:Young Adult; D019061:src-Family Kinases / Q000235:genetics; D000099161:Kcnj11 Channel
chemical_list: D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; D051539:Hepatocyte Nuclear Factor 1-beta; D051557:Hepatocyte Nuclear Factor 4; D018398:Homeodomain Proteins; D008049:Lipase; D051761:Paired Box Transcription Factors; D024661:Potassium Channels, Inwardly Rectifying; D012097:Repressor Proteins; D064233:Sulfonylurea Receptors; D015534:Trans-Activators; D019061:src-Family Kinases; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human; C496487:HNF1A protein, human; C496495:HNF1B protein, human; C496592:HNF4A protein, human; C115117:KLF11 protein, human; C093970:NEUROD1 protein, human; C491709:PAX4 protein, human; C084010:pancreatic and duodenal homeobox 1 protein; C584409:BLK protein, human; C054621:CEL protein, human