Genic Intolerance to Functional Variation and the Interpretation of Personal Genomes

A central challenge in interpreting personal genomes is determining which mutations most likely influence disease. Although progress has been made in scoring the functional impact of individual mutations, the characteristics of the genes in which those mutations are found remain largely unexplored. For example, genes known to carry few common functional variants in healthy individuals may be judged more likely to cause certain kinds of disease than genes known to carry many such variants. Until now, however, it has not been possible to develop a quantitative assessment of how well genes tolerate functional genetic variation on a genome-wide scale. Here we describe an effort that uses sequence data from 6503…

• MR
  Medical Research Council
• NH
  National Health and Medical Research Council
• NH
  National Heart, Lung, and Blood Institute

  Awards: HL-102924, HL-103010, HL-102923