Systematic identification of causal mutations in Mendelian disorders using exome sequence data

Abstract

Exome sequencing has proven to be a powerful and cost-effective approach for the identification of causal mutations in many patients suffering from rare, severe Mendelian diseases. However, exome analysis unambiguously identifies a causal mutation in only 30–50% of sequenced families, indicating much work remains to be done to increase the yield of causal variants from sequencing-based approaches. Causal mutations can be missed by current exome sequencing approaches for a variety of reasons. Conversely, there may be multiple gene candidates that require further information to prioritize for functional studies.We describe the development of an integrated pipeline for the identification of cau..