Exome

The exome is all the exons of all the genes in a genome, taken together. Exons are the stretches of a gene that remain in messenger RNA after splicing removes the introns, and most of them carry the code for proteins. In humans the exome spans roughly 20,000 protein-coding genes yet only 1 to 2 percent of the total DNA, which runs to about 3 billion base pairs.

Despite its small size, the exome holds most of the variants known to cause inherited disease, so reading it is an efficient shortcut. In whole-exome sequencing (WES), short DNA or RNA probes fish the exon fragments out of a DNA sample, and these are then read by next-generation sequencing. This costs less and produces far less data than whole-genome sequencing, but it misses changes in introns and regulatory regions that can also cause disease, and it covers some exons poorly.

Exome sequencing is widely used to diagnose rare genetic disorders and unexplained developmental delay and to find mutations in tumors. An early landmark came in 2010, when it revealed the cause of a severe bowel disease in a young boy and pointed doctors to a curative bone marrow transplant. Like any broad test, it can turn up variants of uncertain significance and incidental findings about other conditions.