When we talk about DNA sequencing, most of the times we refer to the sequencing of the exome rather than the genome. So what’s the difference? While the genome is the entire DNA found inside our cells, the exome represents only 1.5 % of it – made by several specific regions, scattered across the whole DNA. The peculiarity of these regions is that most of the mutations related to diseases (at least those known until now) are located here, making the exome extremely helpful for medical purposes. What makes those fragments so special? They are the EXONS (EX-pressed regi-ONS), the areas of genes that specifically carry information to produce proteins, the molecules essential for the correct functioning of cells and organisms. A mutation or a mistake in one of these exons might disrupt the correct function of the protein and cause a disease. From here, it’s already obvious that, besides exons, there are other areas of DNA which don’t code for proteins (more in future posts). Some of these areas are located inside the genes but are cut out when the genetic code is translated into proteins, leaving the exons alone, in a process called splicing.
Sequencing the exome is cheaper than the whole genome because of its smaller size, but still, it carries essential information for applications of the P4 medicine (Prediction, Prevention, Personalization, Participation). One famous example was covered by an extensive reportage on the Milwaukee Journal Sentinel that won the Pulitzer Prize for explanatory reporting in 2011. The happy ending story tells about a 4 years old boy, Nicholas Volker, who had severe bowel problems and underwent more than 100 surgeries – without any relief for his symptoms. Nic was then in the process of dying. The doctors, totally lost about the diagnose, decided to sequence the exome to find out possible gene mutations responsible for such illness – they found 16,124 mutations and narrowed them down to just one: a defect, never detected before, in one important immune gene (XIAP in the X chromosome), which suggested that the boy’s condition could be treated with a bone marrow transplant. And that’s exactly what they did, leaving the boy perfectly healthy.
This is a very special case, but nowadays exome sequencing still is the cheapest and fastest option to start exploring the information hidden inside the DNA.