Identifying long indels in exome sequencing data of patients with intellectual disability

Abstract

Exome sequencing is a powerful tool for detecting both single and multiple nucleotide variation genome wide. However long indels, in the size range 20 - 200bp, remain difficult to accurately detect. By assessing a set of common exonic long indels, we estimate the sensitivity of long indel detection in exome sequencing data to be 92%. To clarify the role of pathogenic long indels in patients with intellectual disability (ID), we analysed exome sequencing data from 820 patients using two variant callers, Pindel and Platypus. We identified three indels explaining the patients clinical phenotype by disrupting the UBE3A, PGAP3 and MECP2 genes. Comparison of different tools demonstrated the importance of both correct genotyping and annotation variants. In conclusion, specialized long indel detection can improve diagnostic yield in ID patients.