But it will have to wait until he completes the second phase of ExAC.


Due to be unveiled at the ASHG meeting in Vancouver, Canada, this month, it will double the data set's size to 135,000 exomes and include some 15,000 whole-genome sequences, which should allow researchers to explore mutations in regulatory regions of the genome that are not captured by exome sequencing.


ExAC is quietly becoming a standard tool in medical genetics.


Clinical labs around the world now check it before telling a patient that a particular glitch in their genome might be making them ill. If the mutation is common in ExAC, it's unlikely to be harmful.


Geneticist Leslie Biesecker at the US National Human Genome Research Institute in Bethesda, Maryland, says that his lab uses ExAC daily in patient care.

"It's a critical factor that we take into consideration for every variant," he says.

He and other geneticists are now embarking on a painstaking reckoning with the genetics literature that will probably take years.


ExAC has also driven home a point that Goldstein and other researchers have made repeatedly:

that failing to include people from Asian, African, Latino and other non-European ancestries is holding back understanding of how genes influence disease by limiting the view of human genetic diversity.

There is now a fresh impetus to include under-represented groups in planned studies linking genetics and health information on large numbers of people, such as the US Precision Medicine Initiative.


For Vallabh and Minikel, ExAC provided a disheartening confirmation, but also some promising insight.


Minikel's studies have identified 3 three people in ExAC with mutations that should silence one of the two copies of the prion protein gene. If they can live with a limited amount of functioning protein, perhaps a drug could be made that would silence the defective protein in Vallabh, preventing prion aggregation and disease progression without dangerous side effects.


Minikel got in touch with one of the individuals, a man in Sweden, who agreed to donate some cells for research.


Minikel and Vallabh have now joined the lab of biochemist Stuart Schreiber at the Broad Institute, where they are working full-time to find candidate drugs to treat prion disease.


The couple exemplifies the challenge of translating ExAC data into real medical benefits.

"We can't go back from this," Vallabh says. "We have to go through it."

Their situation couldn't be more illustrative of what is at stake: Vallabh is now 32 - just 20 years younger than her mother was when she died.


She has no time to waste.