One Man’s Exons: Craig Venter’s Genome Offers Clues About the Future of Personal Genomics

What we know today about the correlation between genetic variation and observable effects on people’s health, physical appearance and other traits is just the tip of the iceberg, according to a paper published Friday in PLoS Genetics.

The paper analyzes Craig Venter’s exons – the parts of the genome that encode proteins. Venter, who is director of the J. Craig Venter Institute, published his complete genetic sequence last year.

As the only readily interpreted portion of the genome, exons are of natural interest to scientists. That interest is greatly magnified by the fact that variations in these protein-coding regions often translate into structural changes in the molecular machinery of life.

The PLoS paper identified 12,500 places in Venter’s exons where some type of genetic variation affected a protein’s sequence of amino acid building blocks. The vast majority of those cases – about 10,400 – were single-letter variations of the same type that 23andMe analyzes through its Personal Genome Service.

Further analysis narrowed that list down to about 1,500 single-letter variations the researchers considered likely to make a substantial difference in protein function. But in most of those cases science currently has no idea what, if any, effect the variation might have in terms of health or other traits.

For example, Venter appears to have an unusual genotype on both copies of a SNP in PCSK9, a gene that plays a role in cholesterol metabolism. Mutations in other parts of the gene have been known to cause high cholesterol. So it would be a good guess that this variation in Venter’s genome may be having an effect on his cholesterol level, which is elevated enough that he takes statins. But a guess is all it would be. Much more research has to be done before science has a firm grip on which variations actually make a difference to a person’s health.

The new paper also suggests a lot of those variations with health significance are likely to be rare. Though there has been a cornucopia of common variations with observable consequences in the past couple of years and there are plenty more yet to be discovered, Venter’s genome suggests that rare genetic glitches are likely to be more important for any given individual. Finding those rare variations is yet another scientific challenge that has yet to be met.

Progress is being made, however. The 1000 Genomes Project, an international effort to sequence the exons of 1,000 individuals, could go far toward cataloging and beginning to understand some of the human genome’s rarer variations.

So stay tuned. One of our primary goals at 23andMe is to keep up with the latest advances in genetics and use whatever technology is available to make them relevant for our customers.

Photo by Michael Janich