Impact of exome sequencing in inflammatory bowel disease

Abstract

Approaches to understanding the genetic contribution to inflammatory bowel disease (IBD) have continuously evolved from family- and population-based epidemiology, to linkage analysis, and most recently, to genome-wide association studies (GWAS). The next stage in this evolution seems to be the sequencing of the exome, that is, the regions of the human genome which encode proteins. The GWAS approach has been very fruitful in identifying at least 163 loci as being associated with IBD, and now, exome sequencing promises to take our genetic understanding to the next level. In this review we will discuss the possible contributions that can be made by an exome sequencing approach both at the individual patient level to aid with disease diagnosis and future therapies, as well as in advancing knowledge of the pathogenesis of IBD.

Keywords: Sequencing; Exome; Genetics; Inflammatory bowel disease

Core tip: The genetic understanding of inflammatory bowel disease (IBD) has progressed over the last twenty years as new technologies and analytic techniques have become available. The nascent revolution in next-generation sequencing will enable us to sequence the exome - all the protein coding genes in the genome - in thousands of individuals. This review discusses the implications of this new approach for diagnosis in very early onset IBD and as a tool to gain understanding of the hereditary basis of the common polygenic form of the disease at the population level.