When DNA Differences Matter

From Scientific American:

The database is known as ExAC, and I had my first experience with it after I got my genome sequenced. For a few weeks, I brought it from one lab to another to ask scientists to help me make sense of it.

Their analysis brought up a doozy of a finding. I have a variant in a gene for heart muscles, called DSG2. Some studies have indicated that having a variant in just one of your two copies of DSG2 can cause a rare condition called arrhythmogenic right ventricular cardiomyopathy. It leads to sudden, lethal heart attacks; there is no cure.

I learned about my variant from Dr. Robert Green, a clinical geneticist at Harvard Medical School, and his colleague Matthew Lebo, the director of bioinformatics at the Laboratory for Molecular Medicine at Partners HealthCare. As they told me about its terrible reputation, a dark cloud of dread rolled over me as I learned more about DSG2.

But then—with the help of ExAC—Green and Lebo swiftly erased the cloud from the sky.

ExAC (short for the Exome Aggregation Consortium) is a compendium of genetic information that went online in October 2014. It contains every variation in every protein-coding gene in over 60,000 people. It’s about 10 times bigger than the previous database of its kind and contains about 10 million variants—so big that it is giving scientists a much more realistic vision of how we differ from each other genetically.

Green and Lebo visited the ExAC website to evaluate my DSG2 variant. They could instantly see that around 1 in 200 people of European descent carry it as well. That rate is far higher than the rate of arrhythmogenic right ventricular cardiomyopathy.

Green and Lebo diagnosed my variant as likely being benign.

ExAC has been steadily attracting a growing audience of scientists and doctors since its …

Continue Reading