Although the human genome has now been mapped using numerous techniques, some parts remain resistant to accurate sequencing, nearly as mysterious as parts of the world once marked with sea monsters and dragons by 13th-century mapmakers.
Now, a team co-led by Rachel Goldfeder, a Stanford graduate student in biomedical informatics, has identified sections of human disease genes that are difficult to sequence consistently. A report describing the research appears this week in the journal Genome Medicine.
The study found, for example, that the well-known BRCA2 gene — which includes variants thought to nearly quadruple the risk of developing breast cancer — includes sections of DNA that are hard to sequence.
This could be problematic if genetic tests for these gene variants lead doctors to think that some patients have the disease-causing version of the gene when actually they don’t — or to think that other patients don’t have the disease-causing version when in fact they do.
The team of researchers — which included collaborators from the National Institute of Standards and Technology — wanted to find out how many medically important genes were in regions prone to poor sequencing.
The good news was that more than 77 percent of the human genome can be reliably sequenced using current sequencing technology.
The bad news was that nearly a quarter of the protein-coding regions of disease genes are not being sequenced reliably and consistently.
The future of precision health will depend on more consistent and accurate sequencing in these difficult regions. Indeed, Goldfeder and the NIST team write that their work is a "call to arms for those interested in clinical-grade technical accuracy for genome sequencing." They recommend a push to find better ways to sequence all of these tricky parts of the genome.
“As this technology moves from the research lab to the clinic, we need to be able to accurately and reliably sequence entire genomes, because incorrect sequence information can lead to inappropriate medical care," Goldfeder said in a statement. "The challenge now is to focus our efforts on the other 23 percent — namely, on regions of the genome that remain elusive.”
Previously: “An extremely interesting time to be a geneticist”: Using big data to identify rare diseases, Collecting buried biomedical treasure – using big data
Image of 1260 Psalter world map courtesy of Wikimedia