The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity

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Mutations in noncoding sequence can cause disease but are very difficult to recognize. Here, we present two approaches intended to help identify noncoding regions of the genome that may carry mutations influencing disease. The first approach is based on comparing observed and predicted levels of standing human variation in the noncoding exome sequence of a gene. The second approach is based on the phylogenetic conservation of a gene’s noncoding exome sequence using GERP++. We find that both approaches can predict genes known to cause disease through changes in expression level, genes depleted of loss-of-function alleles in the general population, and genes permissive of copy number variants in the general population. We find that both scores aid in interpreting loss-of-function mutations and in defining regions of noncoding sequence that are more likely to harbor mutations that influence risk of disease.

Vyšlo v časopise: The Intolerance of Regulatory Sequence to Genetic Variation Predicts Gene Dosage Sensitivity. PLoS Genet 11(9): e32767. doi:10.1371/journal.pgen.1005492
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005492

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