A group of scientists in the U.S. have shown the feasibility and value of a new strategy for identifying relatively rare genetic variants that may cause or contribute to disease.
In a study supported by the National Institutes of Health (NIH), they tested the strategy that involves isolating and sequencing all exons which are the parts of the human genome that contain the information needed to produce proteins, the building blocks of the body.
The researchers say that the complete set of exons called the "exome"-which makes up only one percent of the human genome-can be sequenced to obtain the important information about an individual at a much lower cost than sequencing a person's entire genome.
They have revealed that assessment of the results of exome sequencing is based on knowledge of the genetic code, and allows for a more informative interpretation of genetic variants.
According to them, the exome strategy can also be helpful in detecting rare variants that typically provide a stronger indication of disease susceptibility.
The research was carried out as part of The Exome Project, a program established to develop, validate, and begin to apply a cost-effective, high-throughput approach for exome sequencing that can be deployed in large, well-phenotyped human populations.
"This focused approach will yield information that informs our understanding of the genetic basis of diseases, a prerequisite for personalized medicine," Nature magazine quoted Dr. Elizabeth G. Nabel, the Director of the National Heart, Lung, and Blood Institute (NHLBI), as saying.
"We have great hope that targeted sequencing, when applied to a larger number of individuals, will be used to discover the genetic underpinnings of common conditions such as high blood pressure and high cholesterol. The current findings provide the fundamental groundwork for pursuing this important goal," she said.
The researchers said that comparing the exome sequences to the publicly available human genome sequence highlighted the sensitivity of this technique for detecting genetic variations, both common and rare.
During the study, they were able to identify a range of these DNA misspellings, such as rare and common single letter variations known as single nucleotide polymorphisms, or SNPs, and insertions and deletions of sequences within genes.
From the DNA of the four people with Freeman-Sheldon syndrome, the researchers were able to pinpoint the causal genetic variant by applying a multi-step systematic strategy to filter out common variants and variants that were specific to each individual.
Based on their findings, the researchers came to the conclusion that sequencing the exomes of a small number of unrelated individuals with a disorder that is due to a single gene can serve as a genome-wide scan for the causative gene.
Within large population studies, the researchers suggest that exome sequencing could be used to uncover genes that contribute to the risk for more common, multigenic diseases such as diabetes or cancer.