Journal article

The intolerance to functional genetic variation of protein domains predicts the localization of pathogenic mutations within genes

Ayal B Gussow, Slave Petrovski, Quanli Wang, Andrew S Allen, David B Goldstein

GENOME BIOLOGY | BIOMED CENTRAL LTD | Published : 2016

Abstract

Ranking human genes based on their tolerance to functional genetic variation can greatly facilitate patient genome interpretation. It is well established, however, that different parts of proteins can have different functions, suggesting that it will ultimately be more informative to focus attention on functionally distinct portions of genes. Here we evaluate the intolerance of genic sub-regions using two biological sub-region classifications. We show that the intolerance scores of these sub-regions significantly correlate with reported pathogenic mutations. This observation extends the utility of intolerance scores to indicating where pathogenic mutations are mostly likely to fall within ge..

View full abstract

University of Melbourne Researchers

Grants

Awarded by National Institute of Neurological Disorders and Stroke of the National Institutes of Health


Awarded by NIH Epi4K Sequencing, Bioinformatics and Biostatistics


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Awarded by NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES


Awarded by NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE


Funding Acknowledgements

ABG is supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number F31NS092362. SP is a National Health and Medical Research Council of Australia (NHMRC) (CJ Martin) Early Career Fellow. This work was supported in part by the NIH Epi4K Sequencing, Bioinformatics and Biostatistics Core grant number U01NS077303. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in design, in the collection, analysis, and interpretation of data; in the writing of the manuscript; in the decision to submit the manuscript for publication.