Exome and genome sequencing

How about the new and hot developments in high-throughput sequencing (including the “next-generation” and “third-generation” methods) that promise to make sequencing thousands of whole genomes feasible in terms of time, infrastructure required and costs? At the time of writing there is only one published pioneering study using such methodologies to investigate the genetic architecture of language and speech (Worthey et al., 2013), but it is to be expected that in the near future they will provide a sizeable proportion of unexpected and exciting new discoveries (see also Deriziotis and Fisher, 2013).

In a nutshell, it is feasible to sequence somebody's whole genome (or just the protein-coding part of it covering only the exomes – the wholeexome) and, in principle, we could look at any characteristics of the person's genome/exome and her/his phenotype of interest. However, this soon runs against a possibly unexpected problem, namely that individual genomes harbour a lot of variation, some of it shared by a sizeable proportion of the population (representing the so-called polymorphisms, usually taken to be those variants appearing in more than 1% or 5% of the population, SNPs being one example), but also some appearing only in a very few other individuals (such as other family members), being thus rare, and yet others specific to the individual (de novo mutations).