New genome-based technology for the diagnosis of rare genetic illnesses is moving rapidly from research laboratories into general medical practice.

Two leading geneticists outlined what health care providers need to know in order to use the new technology effectively in the New England Journal of Medicine (2014; doi:10.1056/NEJMra1312543).

The primer, written by Leslie G. Biesecker, MD, of the National Human Genome Research Institute in Bethesda, Maryland, and Robert C. Green, MD, MPH, of Brigham and Women’s Hospital and Harvard Medical School, in Boston, Massachusetts, offers guidance for physicians to follow when using these new technologies.  

Continue Reading

Health care providers must learn which disorders are appropriate for such testing, what family histories suggest a single-gene cause, and how to interpret ambiguous results when a test points to a gene or several genes that might be responsible.

Already, several thousand physicians have ordered clinical genome or exome sequencing (CGES) for their patients. Approximately 10,000 tests will be ordered this year and even more next year.

Exome sequencing is an abridged version of the more complete and more costly genome sequencing. Instead of sequencing the entire 3 billion base pairs of a person’s genome, exome sequencing focuses on the DNA segments (exons) that code for proteins. These make up 1% to 2% of the human genome and account for approximately 20,000 genes. A patient’s DNA is extracted and the exons are sequenced, then computer programs identify differences between the patient’s DNA and a reference sequence for the human genome. These variations may point to gene mutations that cause the patient’s disease.

In a previous study, exome sequencing identified the genetic cause of disease in approximately 25% of patients. The technique has identified genetic variants in a wide range of conditions, including Charcot-Marie-Tooth disease, mental retardation, neuropathies, metabolic disorders, epilepsy, cardiomyopathy, cancer, and amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease).

“This is a transformative moment in the history of medicine as we begin to integrate genome sequencing into the care of patients,” said Green. “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.”

Whether health insurance companies will pay for genome or exome sequencing is unclear. So far, insurers have covered the tests in some cases.

Some experts have questioned whether genome and exome sequencing is ready for broad application and whether the medical community is well enough versed in genetics to recognize the strengths and weaknesses of the testing. The authors note that, ready or not, the technology is here, physicians are ordering genome and exome sequencing for their patients, and use will only increase.