February 10, 2014 Hi Jeffrey, Thanks for taking time out of your schedule to talk on the phone and sorry for the delay in getting you this invoice. I enjoyed discussing what we can potentially do on the research side with the samples you've already submitted through the PGP. You're probably inundated with proposals on a regular basis - so, to recap some of the general points we discussed: I. George Church recommended me to you through your participation in the PGP and I helped with sample collection and consenting through that study. 2. You have a math background and a long history of supporting the sciences. My impression is your interests could be considered self-discovery using the latest in genomics tools: including a) sequencing, b) data analyses and storage, and c) genomic and functional manipulation of your own iPS and other cell lines. The PGP was supposed to facilitate all these pursuits. 3. To the best of my knowledge, work on your samples are on an indefinite hold with the pgp. Meanwhile, my own involvement with the PGP has weaned off in order to pursue my own genomics research study at MGH that would be decidedly more: a) Clinical:, obviously as a physician this is an important aspect for me but, perhaps even more importantly, the recent ACMG recommendations (see attached) make it obligatory for clinicians to report back incidental findings on these genes - even when sequencing was done on a healthy relative to diagnose a family member with a mutation in a different gene(s). Since there's no intrinsic reason to treat the genetic results of a healthy patient getting sequenced for clinical reasons (eg, a sick family member) differently from a healthy participant in a clinical genomic research study, researchers will need to strongly consider returning these results in a responsible way that helps steer research subjects toward appropriate medical management when indicated by worrisome results (especially when occurring in the 56