Gene-specific function prediction for non-synonymous mutations in monogenic diabetes genes.

TitleGene-specific function prediction for non-synonymous mutations in monogenic diabetes genes.
Publication TypeJournal Article
Year of Publication2014
AuthorsLi, Q, Liu, X, Gibbs, RA, Boerwinkle, E, Polychronakos, C, Qu, H-Q
JournalPLoS One
Date Published2014
KeywordsAdolescent, Apoptosis Regulatory Proteins, Basic Helix-Loop-Helix Transcription Factors, Cell Cycle Proteins, Child, Computational Biology, Diabetes Mellitus, Type 2, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta, Hepatocyte Nuclear Factor 4, Homeodomain Proteins, Humans, Lipase, Mutation, Missense, Paired Box Transcription Factors, Potassium Channels, Inwardly Rectifying, Repressor Proteins, src-Family Kinases, Sulfonylurea Receptors, Trans-Activators, Young Adult

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.

Alternate JournalPLoS One
PubMed ID25136813
PubMed Central IDPMC4138110
Grant ListU54 HG003273 / HG / NHGRI NIH HHS / United States

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