Structural variant identification and characterization.

Abstract

Structural variant (SV) differences between human genomes can cause germline and mosaic disease as well as inter-individual variation. De-regulation of accurate DNA repair and genomic surveillance mechanisms results in a large number of SVs in cancer. Analysis of the DNA sequences at SV breakpoints can help identify pathways of mutagenesis and regions of the genome that are more susceptible to rearrangement. Large-scale SV analyses have been enabled by high-throughput genome-level sequencing on humans in the past decade. These studies have shed light on the mechanisms and prevalence of complex genomic rearrangements. Recent advancements in both sequencing and other mapping technologies as well as calling algorithms for detection of genomic rearrangements have helped propel SV detection into population-scale studies, and have begun to elucidate previously inaccessible regions of the genome. Here, we discuss the genomic organization of simple and complex SVs, the molecular mechanisms of their formation, and various ways to detect them. We also introduce methods for characterizing SVs and their consequences on human genomes.