Public Genomes: Expert Q&A

Q: How do you decide who to include in the 100,000? And when do you expect the project to develop a practical application? Jim McGuire, Somerset, Ohio

Q: They aim to recruit 100,000 people. How many have they recruited to date, and how have they done the recruiting? Anonymous

Church: We have 17,000 people who have registered so far. Recruitment and inclusion criteria will probably change as the project grows, but currently the requirements include age over 21, U.S. residence, ability to visit a PGP-collaborating clinic, and ability to demonstrate understanding of the potential risks and benefits by way of a short test. The first practical applications are beginning to arrive already in the form of open-source community software that connects personal genome sequences with currently predictable and actionable genetic diseases. This software, called Traitomatic, has been used in a research report in the July 8 issue of the journal Nature and in commercial settings.

Q: Dear Sir:
How long does it take to sequence an entire genome? And how does this compare to the time it took with the human genome project? Kudos to you and your team on what you're trying to accomplish. Anonymous

Church: It took 15 years and $3 billion to complete the first genome. It now takes only a few weeks and costs $5,000. This drop in cost is mainly due to radically new technologies published in 2005 and since then.

Q: I would like to participate. Are you keeping specific identities private, or, if not, then why is such disclosure necessary? Robert Osberger, Washington, D.C.

Q: Will the information collected in your study be available to the public with the names of the participants and their personal genetic profile? I would enjoy participating, but not if my information will allow anyone to have this personal information. Anonymous

Church: The PGP does not require the inclusion of names, but we emphasize that, like most other modern medical-genetic research studies, it involves highly identifying traits and DNA data and many ways that these can become public despite initial intentions. We have found many volunteers who understand this and are willing to accept the likely identifiability of their data. This approach seems better for the volunteer community and is of great benefit to the sharing of research results.

Q: Would you suggest a person have DNA test(s) done if they don't have any family (genetic) information because they were adopted? What if an adoptee is thinking about having children? Do you think it is right for genetic information to be withheld from people? Anonymous

Church: From a clinical standpoint, DNA tests are more informative if you have indicators of familial traits. On the other hand, if you have no family information, then genome sequencing could fill that void. There is relatively little experience with this, though, and hence we need projects like PGP to determine the relationships between traits and DNA variation with and without family indicators.

Q: Is there a "legitimate" genome testing company in Canada? Or, for that matter, in the U.S.? Please make recommendations. Thank you.

By the way, I am just completing my 80th orbit around our glorious sun. Theo Dimson, Canada

Church: There are about 1,500 DNA tests that are highly predictive and medically actionable. The agencies providing these tests are CLIA-approved [meaning they meet clinical laboratory testing standards set by the U.S. government's Clinical Laboratory Improvement Amendments (CLIA) of 1988] and geographically diverse, and the tests do not need to be done locally (see http://genetests.org). Clinical geneticists typically determine which of these is warranted based on family history and then choose an appropriate test laboratory.

Q: In November 2007, I sent in my $115 to become a participant in the National Geographic human genome project. What is the status of that project, and where can I keep abreast of its progress? Anonymous

Church: This project is focused on ancient human migrations and not on human traits or medical consequences. The DNA data collected is only about a dozen bits of DNA—less than a millionth of the whole genome. For more information, see: https://genographic.nationalgeographic.com/genographic

Q: In the NOVA scienceNOW program, Neil deGrasse Tyson assures us that health-insurance companies cannot discriminate based on DNA. But if someone's DNA were publicly available as you're planning, what would stop such companies from examining that person's genetic code and, without acknowledging that they had done so, making decisions about that person's coverage based on the company's surreptitious examination? Thanks. Anonymous

Church: The Genetic Information Nondiscrimination Act of 2008 makes it illegal. While companies occasionally do break laws, this would be like breaking a law in order to deny astronauts insurance. Since PGP volunteers constitute a tiny fraction of the world population, and since they are considered altruists, it would be bad public relations and foolish business prioritization as well as illegal.

Q: How long does it take to get DNA results and how much does it cost? David Bachinsky, Charlotte, North Carolina

Church: There is no cost to participants in the Personal Genome Project, but the cost to the Project is estimated at over $6,000. DNA donors and other PGP volunteers can help raise consciousness and raise funds among their friends, colleagues, and family similar to walkathon participants.

Q: The film shows, with the example of Steve Pinker's non-baldness among other things, that accurately predicting an individual's risk for developing certain conditions or diseases by analyzing their DNA is very much in its infancy at this point. How soon do you think this field will be "grown up"? That is, how soon can each of us know to a reasonable degree of assuredness (and, of course, for a certain price), just what likely lies in store for us health-wise in our lives? Thanks. Hari Singh, Toronto, Ontario, Canada

Church: As noted above, there are about 1,500 DNA tests that are highly predictive and medically actionable (see http://genetests.org). These do not include baldness and many other traits, but the measure of new technology is what it can do. The costs of sequencing have dropped exponentially at 10-fold per year for the past four years, and projects like the ones discussed in this film are greatly increasing the interpretation breadth and accuracy.

Q: Both my maternal grandfather and my mother had dementia in their old age. Getting it is my worst fear. Would DNA testing be feasible? Regardless, I would like to volunteer for your genome test group. Thank you. Anonymous

Church: DNA testing for several genes involved in Alzheimer's risk is already feasible. Volunteering at http://personalgenomes.org should be done before the onset of significant symptoms.

Q: What is more challenging, doing the sequencing or analyzing the code for useful information? John

Church: The sequencing is currently the most expensive part of the Personal Genome Project so far. The social challenges of obtaining comprehensive trait data and properly consenting volunteers for sharing such data was initially quite challenging, but for now seems manageable.

Q: I am 45 years old and have fibromyalgia and polymyalgia. My mother, who is 65, has them also. I have two daughters, 23 and 11. There is not enough information about preventing these conditions. I am especially concerned that I have gotten them at such a young age. Is there information that your study could possibly find about these conditions which might help my daughters avoid them? Could you benefit from studying our DNA? Mary Jones, Houston, Texas

Church: The Personal Genome Project cannot guarantee results on a rigid time frame for any particular genetic variation but is certainly intended to address a large set of such disorders by gathering data and cells from large cohorts of volunteers in order to get adequate statistics.

Q: Dear Dr. Church:How will you even begin trying to understand the genetic factors behind something as complex as heart disease?

Also, will you be trying to get a sense of the genetics behind such things as intelligence?

Thank you. Mark Richardson, Portland, Maine

Church: The Personal Genome Project certainly includes heart disease and many other common and complex diseases. The complexities often become much more manageable when the causative DNA variants are found. For example, heart disease gets divided into 1) hypertrophic cardiomyopathy due to heart muscle gene defects, which says that too much exercise can be a problem; and 2) hypercholesterolemia due to lipid synthesis gene defect, which is responsive to altered diet and cholesterol-blocking drugs.

On the second question, there are many genetic variations that greatly affect intelligence—for example, PKU [or phenylketonuria, an autosomal recessive genetic disorder]. These are individually rare but collectively common. The PGP is trying to find additional examples and how genetics and environment interact. For example, in the case of PKU, children are put on Phe-free diets, and what would be a nearly 100% chance of mental disability changes to close to 0%.