An estimated 10,000 genomes and exomes will be sequenced this year in a clinical setting. But all that data only leads to a diagnosis about a quarter of the time. This testing is most useful for patients with rare disorders that result from variants in a single gene, according to a new paper published in the New England Journal of Medicine from two NIH scientists.
Several thousand doctors have already ordered clinical genome or exome sequencing for their patients, said Dr. Leslie Biesecker of the National Human Genome Research Institute, part of the National Institutes of Health. These technologies are often dubbed "whole-genome" or "whole-exome" sequencing. But despite the moniker they don't cover 100% of either. Not all of the DNA can be sequenced and the technique is best at detecting single-nucleotide variants or alterations in sequences of no more than 8 to 10 base pairs. It may not pick up longer variations, repetitions of sequences, or long deletions.
Exome sequencing focuses on the DNA segments, known as exons, that code for proteins. They make up 1% to 2% of the human genome and account for about 20,000 genes.
Genome and exome sequencing are able to identify a genetic cause of disease in only about 25% of patients. The technique has identified causative or contributory gene variants in several diseases, including Charcot-Marie-Tooth disease, mental retardation, other neuropathies, metabolic disorders, epilepsy, cardiomyopathy, cancer and amyotrophic lateral sclerosis (ALS).
"This is a transformative moment in the history of medicine as we begin to integrate genome sequencing into the care of patients," said Dr. Robert Green, who leads the NHGRI-funded MedSeq Project and several other translational genomics research projects at Brigham and Women's Hospital and Harvard Medical School. "While our focus in this article is on the use of sequencing in cases where diagnosis is difficult, the sequence is just the beginning. We can expect these technologies to help us transition our entire approach in medicine to more personalized and preventive care."
The issue of health insurance reimbursement for genome or exome sequencing remains thorny. But insurers have been covering them in some cases. "Anecdotally, some labs are telling us that insurers are reimbursing for these," said Dr. Biesecker. The authors note that all physicians, not just geneticists or specialists, need to be prepared to use genome testing with their patients.
- here's the press release
- read the NEJM article (sub. req.)