Chunk #46 — Gene network inference within individuals using cross-tissue expression variation — Impact of individual gene-disrupting variants on splicing and expression
Assessing the functional impact of DNA sequence variants identified in whole-genome and exome sequencing studies remains a major challenge. Variants predicted to result in the truncation of proteins (splice, stop-gain SNVs, or frame-shift indels) may have large effects on biochemical function, but are also highly enriched for annotation artifacts (43). Errors in predicting the true functional impact of these and other variants can substantially reduce discovery power in common complex diseases and, more important, can affect disease diagnosis in clinical settings (44).
