This month in the journal

摘要

Krumm et al., page 595; Poultney et al., page 607 The role of copy-number variation in complex disease has received substantial interest lately. Many of these recent studies have relied on microarray analysis for calling copy-number variants (CNVs). However, the lower size limit for detection by microarray renders it ineffective for calling CNVs of less than 30 kb, leaving questions about the contribution of these small CNVs to various genetic diseases. Two recently introduced methods of calling CNVs from exome sequencing data circumvent the limits of microarray: CoNIFER and XHMM. In this issue, studies by Krumm et al. and Poultney et al. use CoNIFER and XHMM, respectively, to identify small CNVs associated with autism spectrum disorder (ASD) and validate the accuracy by using transmission information from families with one and two children (trios and quads, respectively). Both studies determined that individuals with ASD had a higher burden of small CNVs (median size 18 kb) than did individuals without ASD. Unlike previously identified large CNVs, small CNVs might only affect a single gene, providing the prospect of refining which individual protein-coding genes, when disrupted, might cause autism. To this end, Krumm et al. found an enrichment of brain-expressed genes and Poultney et al. identified an enrichment of genes involved in the cytoskeleton and autophagy pathways. Not only do these studies highlight new areas for ASD research to explore, but they also emphasize the utility of CoNIFER and XHMM for identifying a range of CNVs from exome sequencing data across a variety of complex diseases.