instagram pinterest linkedin facebook twitter goodreads facebook circle twitter circle linkedin circle instagram circle goodreads circle pinterest circle

Genetic Linkage

Limits of Genome Sequencing Not a Surprise

The news is being trumpeted everywhere – whole genome sequencing won’t help the average person predict common illnesses.

This isn’t exactly astonishing to anyone who has taken a genetics course, but the Johns Hopkins team, in Science Translational Medicine, provides elegant evidence to back up the long-held idea that the so-called “complex," common diseases result from so many intertwined inherited as well as environmental threads that using a DNA sequence as a crystal ball just won’t work – at least until more data accumulate.

The Hopkins report, coming on the heels of the excellent NOVA TV special “Cracking Your Genetic Code” (popularized use of "genetic code" notwithstanding), has caused confusion, judging from some of the comments on the New York Times’s take on the report. How can a TV program celebrate genome (or the shortcut, whole exome) sequencing at the same time that a very rigorous study glaringly reveals the technology’s limitations?

It’s a problem of apples and oranges.

The spectacular successes of whole genome or whole exome sequencing in delivering needle-in-the-haystack diagnoses based on single mutations are a whole different ballgame from tracking the many gene variants that contribute to risk of developing a common cancer or heart disease, illnesses that might not even arise unless specific environmental factors also come into play. It’s the same story as gene therapy: first conquer the rare single-gene diseases about which we know the most, then segue to the more common, the complex.

The Hopkins team investigated 24 common diseases among nearly 54,000 pairs of identical twins. Team member Bert Vogelstein, MD, explained the ages-old approach: “Identical twins share the same genome, and if the genome were the determining factor for common diseases, then the prevalence of a specific disease in an individual whose twin has that disease can be used to determine how well whole genome sequencing could predict an individual’s disease risk.” For 23 of the 24 diseases, having a twin with it did not raise risk above general population values. The researchers coined a useful phrase in this field littered with the hard-to-remember and unpronouncable: genometype: the genomes in a population conferring a specific risk level for a specific disease.

So are whole genome sequencing, and the short-cut whole exome sequencing (just the protein-encoding genes), useless? Not for everyone. Studies are mounting that indicate the value for people with very strong family histories of a common disease, such as pancreatic cancer, or for children such as those on the NOVA special with a never-before-seen collection of specific symptoms. Gavin Stevens, featured on this blog, is a poster boy for children who finally found a diagnosis thanks to DNA sequencing.

But for the majority of us, focusing on the phenotype – symptoms, how we feel – is more important than figuring out our sequences of DNA bases. Sums up Vogelstein, “We believe that genomic tests will not be substitutes for current disease prevention strategies. Prudent screening, early diagnosis and prevention strategies, such as not smoking and removing early cancers, will be the keys to cutting disease death rates.” That, and hitting the gym, eating lots of vegetables, and limiting harmful fats and carbs. Genetics is not medical destiny -- far from it.
Be the first to comment