The Genetic Genealogist

Dr. Wilmot James, head of the African Genome Project and honorary professor of human genetics at the University of Cape Town, is heading a DNA collection project in South Africa. Dr. James is joined by his colleague Himla Soodyall, a scientist at the National Health Laboratory Service and an associate professor in the Division of Human Genetics at the University of Witwatersrand. On September 9^th, James and Soodyall collected swab samples from a number of Capetonians.

The African Genome Project is supported by the South African genealogy website Ancestry24.com (although I was not able to find any information there). One of the goals of the project is to create a public genetic database to examine “how the country became populated over thousands of years” by filling in the gap in current DNA databases.

According to Dr. James:

“No one group can lay claim to South Africa. Everyone is a settler, and we will show how people came here in waves of migration.”

The results are due out in early 2008.

1. Misha Angrist wrote about the implications of personal genome sequencing in “Warts and all.”

2. I think most everyone would agree that affordable whole-genome sequencing will be around long before we understand the information it reveals. I asked another member of The DNA Network, The Gene Sherpa his opinion on the matter. Genome Technology Online also thought it was an interesting discussion. And by the way, the Genome Technology Online’s daily newsletter is a great way to stay up-to-date.

3. DNA Consulting is launching an online forum called DNA Ancestor Communities (from Family Tree Magazine).

4. At Venturebeat: lifesciences, David Hamilton wrote a great post about genome sequencing and insurance – “Personal genomics and the end of insurance.” It received a lot of attention this week, including a mention in Dick Eastman’s Online Genealogy Newsletter.

5. EyeonDNA has a clip of Craig Venter from the Charlie Rose show in 2000, back before Venter was able to browse his entire genomic sequence.

6. Jay Flatley of Illumina revealed more information about future products being offered by 23andMe. Naturally, it received a lot of attention (be sure to read the comments as well):

o I wrote about it here at The Genetic Genealogist;

o VentureBeat: lifesciences wrote an article, and ended with: “Rumors of yet a third, still stealthy, personal-genomics startup are also swirling around the Valley.” Any ideas?

o Another early mention came from Megan’s Roots World, who, like me, picked up on the fact that 23andMe is initially focusing on ancestry.

o business|bytes|genes|molecules wrote an interesting post.

o GigaOM has a very brief mention.

o Genome Technology Online links back to the Forbes article as well.

o Frostfire has a short post and applies the “the Frostfire Buzz Test.”

o A conversation is going on over at Ungrateful Little Bastard.

23andMe has been the subject of much discussion in the biotech and personalized medicine circles of the blogosphere (See here, here, here, here, here, here, here, and here for plenty of information/speculation/discussion).

In August, 23andMe announced (“23andMe and Illumina Forge Consumer Genomics Goliath”) that they have partnered together to offer “consumer genotyping” – more about that in a minute. Illumina produces “SNP chips”, chips that can test a genome for thousands of SNPs (single nucleotide polymorphisms) at a time. For example, the company has one chip that tests one million SNPs for as little as $600, and another chip that tests 550,000 SNPs (the HumanHap550) for only $300-$450. Interestingly, Illumina is also able to custom build chips to add specific SNPs if the customer so desires. Additionally, as the announcement touted, Illumina is also exploring the world of inexpensive whole-genome sequencing, suggesting that this partnership with 23andMe could transition from cheap SNP testing to cheap whole-genome sequencing at some point in the future.

Despite all the conversation and information, the company’s products and services have never been explicitly stated. Although the website states the following, the general public has not known how that would translate into a tangible product or service:

“Our goal is to connect you to the 23 paired volumes of your own genetic blueprint (plus your mitochondrial DNA), bringing you personal insight into ancestry, genealogy, and inherited traits. By connecting you to others, we can also help put your genome into the larger context of human commonality and diversity.”

Yesterday, however, we got a much clearer picture thanks to the Illumina, Inc. Analyst Day in New York City (thanks to Matthew Herper for a great write-up at “Google’s Genetic Start-Up,”). At this meeting, Jay Flatley, chief executive of Illumina, revealed some tantalizing hints about 23andMe’s upcoming launch. Here is a brief outline of the product that has resulted from the partnership between 23andMe and Illumina:

1. Send in a DNA sample (either spit or cheek swab).

2. The DNA is sent to Illumina to for “consumer genotyping”. This means that Illumina uses one of its SNP chips to screen DNA for the presence or absence of certain SNPs, or single nucleotide changes in the DNA sequence.

3. Illumina reports the SNP variations to 23andMe.

4. 23andMe “make[s] that information available through a password-protected Web site” which customers can access to see their personal SNPs.

5. 23andMe will (ultimately) provide information about the meaning or medical/genealogical implication of each individual SNP.

For those of us who are interested in genetic genealogy, It appears that 23andMe’s product might be directed more toward genetic genealogy than medical application:

“Initially, Flatley said, the company will be more focused on ancestry – questions like which parent one got more traits from – than medicine. Many researchers say most genetic discoveries are so far only of limited medical utility.”

Flatley has already scanned his genome and accessed 23andMe’s interface. Additionally, he offered the service free to everyone at the meeting who was willing to sign up (lucky bastards).

You can see the webcast of Jay Flatley’s presentation at Illumina’s website. There hasn’t been much written about this revelation as of today, but I found mention at GigaOM, Genome Technology Online, and Megan’s Roots World.

So what does this partnership between 23andMe and Illumina really mean for someone interested in genetic genealogy? Well, I’m glad you asked. Although some of our personal SNPs are spontaneous, many of them came from either our mother or our father. Genetic genealogists have long taken advantage of SNP inheritance to identify our Y-DNA or mtDNA haplogroup, for example. SNP testing can potentially be one of the most interesting and most lucrative offerings in genetic genealogy, although the field is still in its infancy. Current SNP testing for genetic genealogy, known as “autosomal testing”, involves making conclusions based on a few hundred SNPs and don’t allow something I call “SNP tracking”, the ability to compare SNPs between individuals. 23andMe, potentially, will offer a service that tests million(s) of SNPs, each of which can be individually analyzed and compared.

If you’re interested, here’s a link to a document from the Edge Foundation, a group designed to promote the discussion of intellectual pursuits. The document is a summary (including video links) of a casual meeting between some fantastic scientific minds (Craig Venter, Freeman Dyson, Robert Shapiro, Dimitar Sasselov, and Seth Lloyd) which took place in late August.

Although Dr. Church doesn’t discuss the Personal Genome Project, his brief discussion about our past and our future is very interesting.  There’s also a summary of the meeting from Gregory T. Huang, an invited journalist.  I see that one of the invited guests was Ting Wu, a researcher at Harvard who has initiated the pgEd (personal genetics education project).

I have to say, I am so tired of the United States Postal Service always losing my invitations.

The DNA-NEWBIE mailing list is a great resource for people who are new to genetic genealogy or genetic testing in general. The list provides a forum for questions while promoting education and the sharing of ideas. I primarily use the mailing list to follow current trends or concerns in the field of genetic genealogy so that I can share them here on the blog.

The recent deluge of media attention regarding J. Craig Venter’s diploid genome sequencing prompted one list-member to quote Dr. Edward Rubin: “It’s not clear whether it’ll be 10 years or 50 years, but in our lifetime, [individual DNA sequencing ] will happen.” The list-member goes on to say that it will probably not happen in his lifetime since he turns 75 next month.

Interestingly, the list-member’s statement is addressed by Dr. Kirk Maxey, one of the Personal Genome Project’s “First 10.” Dr. Maxey asserts:

“Don’t bet your whole paycheck on it. Ten people, including me, have signed on with Harvard University gene sequencing Professor George Church to have our entire diploid genomes sequenced. More than that – we will be posting them on the internet for all the world to view. And it should all be finished – before Christmas.”

“For all its complexity, a map of any particular human genome is not really that interesting unless you can also say, “And here is who/what you get from such a blueprint…”.”

“All of the promise of genomics research, the personalized medicine and all the other things, will not be possible unless people are willing to simply bare their genes the same way they are already baring their faces. You are who you are.”

Dr. Maxey makes two great points – we have a long way to go before genomic sequencing provides an appreciable amount of useful information, and we will only obtain that information thanks to the courage of people who are willing to “bare their genes.”

Another list-member asks Dr. Maxey if he knows his Y-DNA haplogroup yet. He responds:

“I am I1a, although this data came from CaBRI and not from the Harvard PGP project. Actually, the full sequencing project is concentrating on disease-associated alleles first. They are not interested in tracing ancestry, but more involved with linking your precise medical and health history to your gene complement.” [Note that I added the hyperlinks for more information - TGG]

And finally, a third list-member asks if the PGP is accepting others for its scale-up, and how he might go about applying. Dr. Maxey writes:

“There is a great deal of discussion now ongoing, not so much about whether to expand the project and get more volunteers, but more about how. I think that they are waiting to see a bit more how this impacts the lives of the first 10 so that they can provide good informed consent to the new ones. It is not something to be taken lightly. Every gene that is reported carries some consequence, especially those that are supposed to predispose one to insanity, early death, etc. It is one impact to know about this yourself, and a completely different one to have your employer and your neighbors looking them up too.”

I think it’s great that Dr. Maxey is participating in the DNA mailing list community and sharing his insight and expertise with these DNA-newbies. This type of sharing and conversation is precisely what is needed to promote the goals of personalized medicine while eliminating fear through education.

I hope to see other members of the PGP mingling with members of the genetic genealogy community. In my opinion, genetic genealogists represent a unique community that should be embraced by the personalized genetics movement. Indeed, genetic genealogists are one of the very few groups of private citizens outside the scientific community who are at the forefront of DNA sequencing and interpretation. They will also undoubtedly be some of the first to explore personalized medicine and whole-genome sequencing.

P.S. – I did check with Dr. Maxey before publishing this interaction, and he thought it was a great idea. I’d like to thank Dr. Maxey again for interacting with the genetic genealogy community.

A very interesting article in the New Scientist published last week by Peter Aldhous examines the approach of affordable whole-genome sequencing. The article mentions 23andme, the recently published genomes of James Watson and J. Craig Venter, and the Personal Genome Project.

“Thanks to the advances in sequencing technology, that might be done for as little as $1000 per person. “DNA chips”, meanwhile, can scan your genome for common “spelling mistakes” for just a few hundred dollars. At that price, the era of personalised genomics is already dawning. “This is the year,” claims [Dr. George] Church.”

Mr. Aldhous’ article doesn’t shy away from the hard stuff either. Although I could potentially obtain my entire genomic sequence if I had $1 million lying around, very little of the information would be interpretable. We still have so very much to learn about our DNA. A great quote comes from Michael Egholm of 454 Life Sciences:

“We’re going to have routine genome sequencing long before physicians know how to make any sense of it.”

Interestingly, Dr. Church believes that people will have at least their protein-sequencing regions sequenced before the $1000 genome is available, at which time they will all “upgrade.” Although I certainly don’t have Dr. Church’s expertise, I’ve always thought that the amount of time between those two events (affordable genome “sampling” and affordable whole-genome sequencing) will be so short that there will be few people who require an upgrade.

HT: Hsien at Eye on DNA.

A news release announces the completion of a DNA collection project by SMGF (Sorenson Molecular Genealogy Foundation) in Mongolia. The goal of the project is to study the descendants of ancient nomads from the Eurasian steppes. The collection was performed in conjunction with the National University of Mongolia and represents “the most comprehensive [DNA collection project] in the history of Mongolia, incorporating all of the country’s geographic regions and major ethnic populations.” In total, more than 3,000 DNA samples and pedigree charts were obtained from 24 different ethnic groups.

According to the news release, the “global fascination with Mongolian icons such as Genghis Khan and Attila the Hun” played a role in promoting the project:

“For many centuries, Mongolians have held an ongoing fascination in genealogy, spurred in part by reverence for ancestors and for oral traditions – with some family and clan names stretching back as far as the 10th Century (AD). Under Genghis Khan’s rule in the 13th Century, Mongols invaded Eurasian territory, then ruled there for more than two centuries. In the 20th century the then-USSR gained political control of Mongolia and its leaders systematically worked to eradicate Mongolian national identity – especially the Khan connection – executing or imprisoning an estimated 100,000 Mongols between 1922 and 1940. In recent years, however, there has been a renaissance of Mongolian national identity, accompanied by a widespread search for Mongolian genetic roots – which the SMGF-NUM partnership will continue to foster.”

Some other goals of the project:

• To study the unique genetic characteristics of indigenous and mixed populations in Mongolia;
• To document and preserve oral histories;
• To add the new historic and genetic data to SMGF’s publicly-available Sorenson Database; and
• To promote family history record-keeping and increase the availability of genealogical record-keeping in Mongolia

Information from the study will be published in “books, journals, and other publications” and will be available on the SMGF website, which is touted as “the world’s leading online repository of correlated genetic and family history information for people throughout the world, which currently contains in excess of five million records from more than 170 countries.”

A few days ago I received the latest Facts & Genes Newsletter from Family Tree DNA.  The newsletter is available on their website and includes the following tidbits:

1. In August the company sent out their 100,000th test kit;
2. The website now has a site map;
3. The company was named one of the 100 fastest growing companies in Houston, and;
4. The newsletter also has a brief segment entitled “Genetic Genealogy: Where to Start“, which might be interesting to some of you who are new to genetic genealogy!

I recently had the opportunity to talk with Dana Waring, a member of Ting Wu‘s lab at Harvard and one of the creators/caretakers of the pgEd, the Personal Genetics Education Project. It was a fascinating conversation about the future of personal genetics and the dire need for more education of the public in this field. You can see a few recent mentions of the pgEd from other members of the DNA Network – EyeonDNA, and genomeboy.com.

I was very interested in Dana’s project, and she was willing to share more information with me and my readers via the following email interview:

TGG: How did you get involved with the Personal Genetics Education Project?

DW: The Personal Genetics Education Project is based in the Wu lab at Harvard Medical School. The main research focus of the lab is in a branch of epigenetics called homology effects, where the presence of homologous sequences can dramatically affect gene expression. Professor Wu wanted to add a new dimension to the lab’s focus, looking at the potential social impact of genetic testing becoming mainstream – personal genome sequencing to be exact. My background in women’s studies, the history of science, and higher education seemed like a good fit to explore some of the ethical, legal, and sociological ways genetics will personally impact people. With the Archon X Prize for Genomics and the Personal Genome Project well underway, it is clear that the science is moving very fast.

I have young children, and being pregnant got me thinking about the intersection of biotechnology and individual lives. During my pregnancies, I was genetically tested for the first time in my adult life, and having to live with various statistical formulas and risk calculations was confusing and frustrating. I wanted things to be black and white, and of course they rarely are. (As any parent will tell you, this is a lesson best learned early on, I suppose). It was a concrete example that what starts off in a basic research lab can impact the most personal and private spheres of a person’s life, and also that understanding “risk” is not easy. As people are able to learn more and more about their genomes, health insurance, reproductive medicine, and how we think about medical privacy may all be turned upside down.

TGG: What are the goals of the pgEd?

DW: Our main goal is to engage young people about the revolution underway in the field of genetics, and help them to think analytically about it. As with many technological innovations, the science is moving faster than the ethical, legal, social, and psychological frameworks.

Through workshops, student clubs, and the curriculums we are developing for teachers, we want to get people thinking about the possible benefits and risks of knowing the details of their genome sequences. They are going to be the professionals who live with and make sense of the massive amount of genomic data coming at us, and hopefully use it to better understand and improve human health. They also will likely face novel choices and dilemmas when it comes to medical care, particularly in the area of reproduction.

I wonder if someday sequencing an embryo (taking preimplantation genetics diagnosis many steps ahead) will be a common part of reproductive medicine. Like many people working in this field, we all keep coming back to the same question. Where do we draw the line? And who gets to draw it?

TGG: The website states that you are “creating materials and conducting education events for high school and college students so that they can become familiar with the ethical, legal, and social issues (ELSI) regarding personal genetics.” Why did you choose this particular age group?

DW: Students in high school and college will become independent health care consumers as personal sequencing hits the mainstream. Will they want to have their genomes sequenced? And how will they share the information they learn? How will the generation considered the most technologically sophisticated and open about their private lives respond? Maybe in the end they won’t embrace openness as everyone thinks the “facebook” generation will. Or possibly they will come to the conclusion that their genomes are no more special or in need of unusual protections than other “personal” topics – relationships, academics, or other medical issues and information.

The first major wave of children born of donor gametes or IVF are coming of age and starting to ask some rather complex questions about their origins, rightfully so. Others are talking about some of the unintended and unforeseen medical and social issues coming to light. We suspect that children born of a new biotechnology such as donor insemination might offer new perspectives and be able to put themselves in the shoes of their future children. How do you balance the parent’s willingness to try out a new technology and the interests of that potential, future child? A lot of our work aims to put future generations of children front and center in the debate. I suspect that personal genome sequencing might have similar issues a generation from now. What would my kids, too young to consent, think if I got myself sequenced and made it public – exposing half of their genetic makeup in the process? And if my husband did too? Maybe they carry something passed on from me that will cause them worry or invite scrutiny they never asked for or wanted. As teenagers, they might find it an egregious breach of their privacy or be furious that I accidentally somehow have limited them in terms of careers, insurability, or something else I haven’t thought of. Or they might not care at all and look back at this interview and laugh at their gloomy old mother – or note that I was worrying about entirely the wrong things. And that’s really the crux of it – I don’t think anyone knows for sure exactly where this will take us. Bringing young people, soon to be the main “users” of their genomes, into the conversation is one of our main purposes for starting the Personal Genetics Education Project.

Lastly, we hope to spark in an interest in non-traditional careers in science. Genome sequencing is just one of the many biotechnologies that will necessitate more people working in the fields of policy, intellectual property, bioethics, counseling, and education, to name just a few!

TGG: Based upon your own experience, what are some of the biggest hurdles in educating the general public about personal genome sequencing?

DW: I don’t think there is much disagreement about the need for new and interesting ways to engage the public on science. I wish it were more commonplace for scientists to be rewarded, career-wise, for teaching and for their outreach efforts. Also, there are just a few of us that are part of the pgEd, but we wish we could do this work on a larger scale! I am sure many people feel the same way about their own work.

One challenge we are finding is that teachers are under enormous pressure to cover a set curriculum and to help students pass various exams that are required by their state. It is not always easy to make room for something like this – Although I will add that the workshops we give could also fit with a history, politics, or current events class!

There are a lot of great public engagement models out there - I am thinking of the Dana Centre in the UK and also the many Science Cafes here in the US. I find that once people hear about personal genomes, almost everyone can dive right into the medical benefits and ethical issues and most often say to me “ Wow. That sounds great. But kind of scary, too. Is it scary or great?”

TGG: Is there anything that those of us with genetic backgrounds can do to help the Project, or help educate the public about the risks and benefits of personal genome sequencing? Do we have an obligation to do so?

DW: Giving me the chance to talk about it, especially as the school year is starting, is great. Thank you! Talking about personal genetics to as wide and diverse an audience as possible is one way to help out. The more people who are invited to the conversation, the better for the field and the better for society. Genetics as a preventative medicine tool is a new idea that will take some time for everyone to get used to.

I think it is crucial that the scientific community, geneticists especially, are careful to not overstate what can be learned from genetic testing and personal sequencing. Personal sequencing will not find “the gene for” many complex traits and multifactorial diseases, whether it be a health-related topic like obesity or heart disease, or intelligence, sexuality, or whether or not you prefer cats or dogs. Of course there are many traits and diseases that have a powerful genetic basis – no disagreement here. More interesting to me is: why are people so drawn to this idea that there is a gene “for” this or that? Biological determinism is an old idea that keeps coming back, new and improved as technology advances. There are historical moments when people seek biological explanations for what I see as social issues and inequities; war, poverty, discrimination, and academic achievement gaps between various races all come to mind. Yes, genome sequencing will likely open up an enormous number of avenues for research into disease and behavior, and shed some light on the interplay of genes and environment. Avoiding the hype, and speaking up when things are being oversimplified or misconstrued will go a long way to helping people weigh the risks and benefits of personal genetics.

I think the pgEd is an interesting and much-needed component of personal genetics, and I thank Dana very much for taking the time to discuss the topic and to share some of her thoughts with us today.

Wow, what a day for personal genetics. Yesterday, J. Craig Venter’s diploid genome was released (I’m not sure where the sequence is, but the paper is available at PLoS Biology, a OPEN ACCESS journal!).

I know that many people have their gripe about Venter, but seeing a story about personal genetics on the front page of CNN is important. It educates people and helps alleviate fears about genomic sequencing. I think it’s a great opportunity for the field. Here’s a few quotes from the CNN story:

“Venter has just published almost all 6 billion letters, or 96 percent, of his own personal genetic code in the journal PLoS Biology. From diseases to personality traits, it’s the most comprehensive human genome to date. Venter’s gene map provides a new understanding of his genetic destiny, according to the DNA inherited from both his father and his mother.

Venter says it’s just the beginning of a new era of personal genomics. “For the first time, we can answer almost any question of what’s genetic, what’s the environment. Our genes can tell us probabilities of what might happen and give us a chance to do something about it.”

There are also some quotes from George Church, leader of the Personal Genome Project:

“Dr. George Church, a professor of genetics at Harvard Medical School, is working on a DNA test that would identify for the consumer 1 percent of his or her DNA at a cost of $1,000. He says that someday soon, people may be checking their DNA maps as they do their stock portfolios — constantly adjusting to everyday developments and new gene discoveries.

“You’ll have all that information sitting at your desk and as the information flows in you’ll say, ‘I only want to know things of certain type. I don’t want to know about Alzheimer’s, or I don’t want to know about heart disease, or I do, or I want to know about everything, as soon as it comes in,” says Church.

It’s a habit Venter already follows. As more genes are discovered, he says, he constantly checks his own genome.”

For all the genetic genealogists out there, our habit will undoubtedly be comparing our genomes in order to find or identify potential relatives. Sure, curing disease and improving health is important, but genealogy is FUN!

The DNA Network has provided LOTS of coverage of the diploid genome release, so check out the following:

• EyeonDNA, here and here.
• Bitesizebio
• SNPedia
• Discovering Biology in a Digital World
• evolgen
• Genomicron
• Scienceroll
• The Genealogue (not a member of the DNA Network).

Whew, that should keep you busy for a while!!