Rare structural variants

Abstract

In this chapter, we will briefly touch on the historical discoveries of large abnormalities in the structure of the human genome. It is now clear that more subtle structural variants are in fact ubiquitous and key to understanding the spectrum of risk for many human diseases. While many of these changes are individually rare, the aggregate burden in the population is significant. With this in mind, we give an overview of the technologies developed to assay these variants in a high-throughput manner at ever-increasing granularity, including array-based platforms and next-generation sequencing. We then focus on whole-exome sequencing, since many disease studies to date have adopted this approach. Throughout, we review some of computer software and algorithms available for extracting structural variant information from experimental data. We conclude with a comparison of the strengths and weaknesses of the various current technologies and provide a small sampling of emerging methods for investigating the range of structural variation in more detail.