The Genetic Genealogist

I received an email from Denis Savard of the E3b Project, asking me to post the following for my readers. For the non-genetic genealogists, E3b is a Y-DNA Haplogroup (info here). The E3b Project was also ISOGG’s “DNA Project Website-of-the-Week” 14 Nov 2007.

Here’s the announcement:

Dear Readers,

The worldwide E3b Project proudly announces a new milestone: reaching the 700 member mark.

Since its launch this past June, the E3b project’s website (http://www.haplozone.net/e3b/project) has been steadily growing and is gradually being transformed into a dynamic place of learning, collaboration and research for all things related to E3b.

Here are some of the new developments from the last couple of months:

+ The new V-Series SNP tests have proven very popular among our E-M78 subclade participants and we have been very successful in further dissecting the E3b1a subclade into several distinct and finer branches. So far, about 70% of M78+ participants have also tested V13

+ (E3b1a2), which is the most prevalent European E3b subclade, and among these a single downstream M224+ (E3b1a2b) was also found. Of the remaining members that have requested the V Series test, 17.7% came back as V22+ (E3b1a3), and 11.4% came back as V12+ (E3b1a1). These and other statistics are periodically updated at the following page: http://www.haplozone.net/e3b/project/page/5

+ This last week the fall edition of the Journal of Genetic Genealogy has published the much anticipated research paper by E3b project’s collaborator Steven Bird, “Y-Haplogroup E3b-V13 as a Possible Indicator of Settlement in Roman Britain by Soldiers of Balkan Origin”. You can find and read this interesting document at this link: http://www.jogg.info/32/bird.pdf

+ Our database has recently been updated to include Elise Friedman’s extended haplotype cluster analysis, an in-house system which enables us to classify E3b haplotypes into well defined clusters based on allele similarities, which normally tend to correlate with biogeographical backgrounds. This focused analysis on individual haplotypes nicely complements the software based output from commonly used software applications that we use to create cladograms and neighbor joining diagrams, etc. Please go to the following page: http://www.haplozone.net/e3b/project/cluster

+ Another important trend in the last few months has been the inclusion of more collaborators who have volunteered to promote the project, to provide guidance to new members and take part in a collaborative effort to spread the new scientific discoveries and findings related to the origin, diffusion and phylogeny of this ancestral haplogroup.

+ Next comes our forum, the Double~Helix community (http://community.haplozone.net/), which has also proven itself as an ideal place for new E3b participants to inquire about their results or exchange their observations. Besides reading the opinions of regular participants, the team at hand will try to point out possible relationships of distinct haplotypes, predict a downstream mutation and identify a specific sub-cluster if enough markers are provided or maybe recommend specific additional testing.

If that wasn’t enough, Dr. Dirk Schweitzer is now preparing a basic guide to E3b, including subclade descriptions, geographic distributions, etc., since most online E3b reference pages currently available elsewhere are already outdated. A public link to this information will be announced here when available.

In sum, there are many exciting new things happening as we speak.

All that has been previously mentioned plus the inclusion of new haplotype data from relevant genetics population studies that enable members to match their haplotypes against a growing dataset is providing all members with new insight about their distant origins and helping us all to understand the bigger DNA picture.

Finally, we wish to thank all the Geographic and Surname Project administrators that responded to our recent request to invite their E3b participants to our haplogroup project. The response has been phenomenal and we’re sure your Project members will thank you for it. Here’s our FTDNA link: http://www.familytreedna.com/public/e3b

Best Wishes To All From The Team At The E3b Project.

In light of the launch of 23andMe and deCODEme, two genomic analysis companies, I recently asked whether or not my readers were interested in analysis of their own genome. The results suggest that of the people who voted, many were interested in the idea. The poll received a total of 51 votes, and I thank everyone who took a moment to cast their opinion (and I was very pleased with how well PollDaddy worked). Here are the results:

It looks as though many people are interested in genomic analysis, and that a significant number have some concerns that must be addressed or resolved before they would consider it.

bbgm had a poll on his blog, with the results posted recently at “Your Personal Health: Readers Vote Yes“. Again, similar to my results, readers were interested in genomic analysis.

It’s not a whole-genome scan or a genetic genealogy test, but it’s still a DNA test from the drug store shelves. Soon you will be able to purchase a paternity test from Rite-Aid.

The test is being offered by Sorenson Genomics. According to an article from Monday’s New York Times:

“A company called Sorenson Genomics has started selling a paternity test kit through Rite Aid stores in California, Oregon and Washington. It appears to be the first time a DNA test is being sold through a major pharmacy chain.”

“The test, sold under the brand name Identigene, has a suggested list price of $29.99, though a reporter purchased one at a Rite Aid in Santa Monica, Calif., for $19.99. There is an additional laboratory fee of $119 to have the samples analyzed.”

The test comes with three sets of cotton swabs, allowing the collection of DNA from the child, alleged father, and the mother. The NYT article states that the mother’s DNA is optional “but helps strengthen the results.”

Discovering Biology in a Digital World asks: “Would the results from this test be legally binding?” I personally can’t imagine that the results would hold up in court. I think that’s why Sorenson Genomics labels the test as giving “peace of mind.” A commentor left the following from an news.aol.com business story: “The kit advises people wanting to test for legal purposes to call the company and set up a chain of custody for the samples, which would cost an additional $20.” Hsien Lei from Eye on DNA also left a comment to the post, adding that home paternity tests are nothing new, which is absolutely true – they’ve been around for a while. But now, for the first time, you can impulse shop, or pick one up on your way home from work.

There is more coverage at Eye on DNA and GenomeWeb.

PLoS Genetics has a new paper (PLoS Genet 3(11): e185. doi:10.1371/journal.pgen.0030185) that examines autosomal microsatellite markers (repeating units of base pairs) from Native American DNA:

“We examined genetic diversity and population structure in the American landmass using 678 autosomal microsatellite markers genotyped in 422 individuals representing 24 Native American populations sampled from North, Central, and South America. The Native American populations have lower genetic diversity and greater differentiation than populations from other continental regions. We observe gradients both of decreasing genetic diversity as a function of geographic distance from the Bering Strait and of decreasing genetic similarity to Siberians—signals of the southward dispersal of human populations from the northwestern tip of the Americas”

From the press release, the data shows that:

“Genetic diversity, as well as genetic similarity to the Siberian groups, decreases the farther a native population is from the Bering Strait – adding to existing archaeological and genetic evidence that the ancestors of native North and South Americans came by the northwest route.”

“A unique genetic variant is widespread in Native Americans across both American continents – suggesting that the first humans in the Americas came in a single migration or multiple waves from a single source, not in waves of migrations from different sources. The variant, which is not part of a gene and has no biological function, has not been found in genetic studies of people elsewhere in the world except eastern Siberia.”

HT: Yann Klimentidis’ Blog and henry on genetics.

Here’s the question: Do people really make “life-changing” decisions based upon the results of a genetic genealogy test? This phrase is often stated but is seldom supported with actual facts or case studies. And I’ve certainly never seen an estimated percentage of people who have made these types of “life-changing” decisions, which would really help further the discussion.

Earlier this month, Harvard Professor Henry Louis Gates, Jr. announced the launch of his new genetic genealogy company, AfricanDNA.com. According to the press release, “the precedent-setting site is the only company in the field of genetic genealogy that will provide African Americans with family tree research in addition to DNA testing.”

The company will offer two tests – the Maternal Test (testing mtDNA) and the Paternal Test (testing Y-DNA). The testing will be done at the Genomic Analysis and Technology Core laboratory at the University of Arizona, led by Dr. Michael Hammer of Family Tree DNA. Results will be compared to Family Tree DNA’s database of DNA results. Customers will also have the option to purchase AfricanDNA.com’s Genealogy Package, which traces the customer’s lineage “as far back as records permit.” From a story in the Wall Street Journal:

“For $888, African DNA, which works with Houston-based Genealogy By Genetics Ltd., will include a family tree as far back as census records allow. For most African-Americans, that is usually 1870, when their last names began to be recorded in post-slavery U.S. records.”

The idea that a person’s mtDNA or Y-DNA can be traced back to a specific location or ethnic group in Africa has been hotly debated for years. As the WSJ article states:

“the large migrations of African people over the last 3,000 years mean that a typical black American’s DNA might have an exact match with somebody living today in Ghana — but also Cameroon, Kenya, Angola, Nigeria and Sierra Leone.”

Yesterday, an article by Ron Nixon in the New York Times entitled “DNA Tests Find Branches But Few Roots” discussed Dr. Gates’ new company. (Sidenote: Nixon writes that “an estimated 460,000 people have taken genetic tests to determine their ancestry or to expand their known family trees, according to Science magazine.” I recently estimated that number to be higher.)

Nixon’s article looks at the scientific feasibility of using the results of genetic genealogy testing to pinpoint a specific location or ethnic group as the source of a person’s mtDNA or Y-DNA. I agree with the general conclusion that this is very difficult (often even impossible) and potentially misleading.

Thus, my disagreement is NOT with the discussion of the science in the article – in fact, I think Nixon does a great job of looking at both sides of the issue. Instead, I disagree with the following from Nixon’s article, quoting Troy Duster (Professor of Sociology at New York University, and one of the authors of the recent editorial in Science regarding genetic genealogy):

“People are making life-changing decisions based on these tests and may not be aware of the limitations,” he added. “While I don’t think any of the companies are deliberately misleading customers, they may have a financial incentive to tell people what they want to hear.” [emphasis added].

This brings me back to my original question: Do people really make “life-changing” decisions based upon the results of a genetic genealogy test?

In my view, there are two basic assertions underlying the “life-changing” statement: (1) people are relying on the results of genetic genealogy tests to make decisions, and (2) these decisions are extremely important decisions (such that they are “life-changing”). For instance, deciding to borrow books from the library about a specific geographic area or researching an ethnic group of people cannot be the type of decisions referred to in articles because they are not “life-changing.”

So what type of decisions are being referred to, and how often are people really making them? Have enough of the supposed 460,000 people who have been tested made such an important decision that it is “life-changing”? As a scientist, I’m skeptical but certainly open to evidence. If you think that this is a real problem, please let me know in the comments why you think so. Or, if genetic genealogy has led you to make a “life-changing” decision, I would honestly like to hear about it.

There’s more discussion of the NYT article at John Hawks Anthropology Blog, “Wherein the New York Times says Hawks was right.” And I’m sure there will be a lot more coverage and conversation among genetic genealogists.

I’m sorry if I’ve overloaded you on the recent launches of 23andMe and deCODEme, but I think there’s so much to talk about. For a little lightheartedness, read “23andMe Party” from How to Change the World by Guy Kawasaki. Kawasaki describes a friends and family “Spit Party” hosted by 23andMe, and even has a number of pictures from the event.

The party offered attendees the chance to submit their DNA for analysis at a discounted rate. Some of the attendees included co-founders Linda Avey and Anne Wojcicki, at least one Nobel Prize winner, and celebrities Goldie Hawn and Kurt Russell.

I have been accused of being a little too thorough sometimes. All things considered, that’s a flaw that I can live with. In the name of thorough, I offer the following review of recent online references to this weekend’s launch of personal genome analysis companies deCODEme and 23andMe. If you’re tired of hearing about the topic feel free to skip this post, but if you’re interested in the conversation that these launches have stimulated, read onward.

Kara Swisher at All Things Digital recently toured the new offices of 23andMe. The article – “Kara Visits 23andMe” – has a brief write-up and three videos. The first video is Ms. Swisher’s tour of the offices and includes an overview of the DNA collection kit and a brief interview with Linda Avey and Anne Wojcicki. The second and third videos are part of a longer interview with Avey and Wojcicki.

My Biotech Life watched one of Kara’s videos and recognized the DNA collection kit being used by 23andMe, from DNA Genotek.

bbgm has a post, “Your personal health: Social networking XY.0 revisited and some killer video”, that discusses the social networking aspect of 23andMe.

Silicon Valley Mom’s Blog has a post entitled “New Gift For Your Mother: A Genome Kit!” Although I almost take offense with the ridiculous (and I think half-joking) idea that “family-tree research is a type of late-life nesting activity in older women”, the author points out that genome analysis might be a new type of narcissism. An interesting idea, although for many people the medical benefits (now and in the future) will outweigh any narcissistic benefits of genomic sequencing.

At David W. Boles’ Urban Semiotic, there is an interesting discussion in the comments following “23andMe and the Ticking Timebomb Within.”

Cyberpunk has their own take on the launch of 23andMe at “Wired Magazine Issue 15.12: Welcome to The Age of Genomics.”

Biomedicine on Display has a post at “23andMe and bio-consumership: the new web-based convergence between bioinformatics, business, and the public engagement with science” that highlights the convergence of numerous technologies in 23andMe’s product.

Bertalan Meskó at Scienceroll recently rated the websites of Navigenics, Helix Health, and 23andMe. Since 23andMe’s website was redesigned as part of their launch, he performed a re-review of the site.

David Ewing Duncan at Portfolio writes a piece about the concerns of personal genome analysis – “The Serious Business of Gene Tests.” Part 2 of Duncan’s series will be published later this week as he “runs his own DNA through the new websites and test-drives this Brave New world of genetic testing.” Duncan is also the author of the popular article about personal genome start-ups which appeared in the November issue of Portfolio, called “Welcome to the Future.”

Between the Lines, a blog at ZDNet, writes “The Online Health Revolution and Your DNA: It’s a Trust Issue.” The trio of authors bring up a number of issues, including the trust required of companies that store sensitive information (such as DNA) in databases.

Next is “Step Right Up, Get Your Very Own DNA Profile, Only $999” from Discovering Biology in a Digital World. The author states that “personal genomes are not just for Venter and Watson anymore,” and asks “is it really such an unequivocally good thing?”

There are two articles from David P. Hamilton at VentureBeat: Life Sciences. The first, “23andMe Lets You Search and Share Your Genome – Today,” highlights the launch and websites of 23andMe and deCODEme. In the second post, “23andMe: Will the Personal-Genomics Company Need Big Pharma to Make Money?”, Hamilton discusses the possible business models for personal genome companies. Aside from what appears to be a minor profit margin on each test, how will these companies monetize their products?

At Pimm, Attila Csordas asks “inF.A.Q. for 23andMe: What if I Have Mitochondrial DNA From Pa?” This questions, of course, is very familiar to genetic genealogists – is mitochondrial DNA ever passed from the father? It’s been discussed at length in the genetic genealogy circles, so I won’t address it here. But the question still gives me shivers sometimes! Attila also discusses 23andMe in two other posts – “23andMe’s mission: connecting all people on the DNA level or social networking XY.0”, and “23andMe: Genetics brings people together, rather than differentiate.”

At DNA and You, Dr. Matt Mealiffe asks “Who’s Your Daddy?” Dr. Mealiffe brings up the possibility of non-paternal events being discovered by personal genome analysis. As those of us in the genetic genealogy circle know, this is one of the major ethical concerns of DNA testing, and one that genetic genealogists have been faced with for many years. It is likely that the problem will be aggravated by increased testing, especially testing within families. A second article from Dr. Mealiffe wonders about the effect of copy number on these types of tests.

This weekend’s launch of deCODEme and 23andMe triggered a trio of polls: the first is found at bbgm’s post “Your Personal Health: A Quick Poll”, the second is at the Seven Stones with “Personal Genomes For a Fistful of Dollars”, and the third is right here at The Genetic Genealogist – “Poll – Are You Interested in Genomic Analysis?”

There are also at least two other ‘round-up’ posts from some of my fellow DNA Network bloggers. ScienceRoll has the first one at “Personalized Genetics: It Has Officially Begun!” The second is at Eye onDNA, with “DNA Network Members Discuss Personal Genomics Service Providers 23andMe, deCODEme, and Navigenics.” Hsien points out that many of the DNA Network blogs were cited in The Genetic Revolution at The Issue.

The Gene Sherpa, who argues that it is too early to put personal genomics in the hands of consumers, has a number of posts including “Cottage Industry? Cottage Cheese is More Like It!”, and “Not With a Bang…The Death of Personalized Medicine”, and “Staying Positive.”

In the popular media, Nicholas Wade at the New York Times has an accompanying piece to Amy Harmon’s article. Wade’s article, “Expert’s Advise a Grain of Salt With Mail-Order Genomes, at $1,000 a Pop,” mentions some of the concerns of genomic sequencing. There’s also a lengthy article in the SFGate entitled “Mountain View Startup Offers DNA Scans Online.”

And finally, at The Great Beyond “It’s All About Me – November 19, 2007.”

There – that should keep you busy for a while.

Given all the recent activity in the field of personal genomic analysis, I was curious about how the readers of this blog felt about having their own genome analyzed. Here’s a poll that will give me a rough idea – please feel free to vote! If you’re reading this through a feed, you might have to stop by the blog to vote.

The Genetic Information Nondiscrimination Act, known in shorthand as GINA, is federal legislation that would prohibit insurance companies from discriminating against an applicant based on genetic information, the refusal to submit genetic information, or for have been genetically tested in the past. The Act, if passed, would also prohibit employers from using or collecting genetic information to make employment decisions. I wrote a GINA Primer in April, if you’re interested in learning more about the Act (here’s the full text of the legislation). The Act, which is currently a bill before the Senate, easily passed the House of Representatives (97% voted aye), and President Bush has said that he would sign the bill into law if it reaches his desk.

In August, I wrote about the stalled status of GINA in the Senate. At that time, a “hold” had been placed on GINA by Senator Tom Coburn, M.D., a Republican from Oklahoma. There was a story about the stall in the Boston Globe (available here) and The Buffalo News (available here).

As an article by Alexis Madrigal in Wired – “Genetic Nondiscrimination Bill Stalled In Senate” – discusses, the bill has still not been voted on in the Senate as a result of Senator Coburn’s hold. According to the article, Senator Coburn has placed the hold because of concerns that “an employer who provides health insurance for its workers could be sued both as an insurer and as an employer.”

In the comments following the Wired story, one commenter mentioned a recent USNews article and brought up the lack of the opposing side’s viewpoint in most discussions of GINA. There’s also a recent article from Xconomy. Links to opposing viewpoints can be found via Wikipedia’s GINA page.

Congresswoman Louise Slaughter, the moving force behind GINA, has more information at her website. I was unable to find a public statement from Senator Coburn.

I have written a lot about the Mountain View based personal genome start-up company 23andMe (February 14^th, April 9^th, June 19^th, July 31^st, and September 13^th, to name a few). As a matter of fact, if you google “23andMe”, The Genetic Genealogist is the second result.

Today, announced by an article in the New York Times (“My Genome, Myself: Seeking Clues in DNA”) and Wired (“23andMe Will Decode Your DNA for $1000. Welcome to the Age of Genomics”), 23andMe has officially launched.

If you visit 23andMe, you’ll notice that the site has been completely revamped, and they are now accepting orders for their Personal Genome Service, for $999.

So what does 23andMe offer? According to the company’s Genotyping Section:

“In all, 23andMe looks at more than 500,000 SNPs scattered across the 23 pairs of chromosomes that constitute the human genetic sequence. We also look at a few thousand places on the mitochondrial DNA, an odd loop of genetic material outside the nucleus that is involved in producing energy for the cell.”

23andMe is using the Illumina HumanHap 55+ BeadChip (more information from Illumina), which

“analyzes more than 600,000 SNPs that cover the entire genome. Although this is still only a fraction of the 10 million SNPs that are estimated to be in the human genome, these 600,000 are specially selected because they provide a lot of information about other nearby SNPs. This maximizes the information we can get from every SNP we analyze, while keeping the cost low….In addition, we have hand-picked more than 30,000 additional SNPs of particular interest from the scientific literature and added them to the chip.”

Once a customer’s DNA is analyzed, the information is loaded into the secure database where it can be accessed and viewed by the customer. In the “gene journal” section of the site, the customer can use “The 23andMe Odds Calculator”, which helps the user understand which “common health concerns are most likely to affect a person with your genetic profile.” It is absolutely vital to note that this calculation is NOT meant to serve as a medical diagnostic or medical advice – it is merely a tool to learn more about an individual’s DNA. The ability of science to predict disease based on genetics is still in its infancy, so 23andMe will continue to update the gene journal with new information and data as it becomes available.

There is additional information on the site for people who are new to genetics, including a Genetics 101 section, and a few relevant educational videos. They also have a section “for the experts” with links and journal excerpts.

So What Does This Mean for Genetic Genealogists?

One of the categories of 23andMe’s Personal Genome Service is their Ancestry section. A customer will be able to use the analysis to learn more about their genetic ancestry. As quoted above, the SNP chip will reveal massive amounts of information about the mitochondrial genome, and about autosomal ancestry (it appears that the company is still working on developing more extensive Y chromosome testing). I was especially impressed by the comparison of mitochondrial information obtained from 23andMe’s test versus that obtained from previous genetic genealogy tests – 23andMe examines over 2,000 SNPs from the entire mitochondrial genome.

23andMe also provides analysis of the individual’s autosomal ancestry. As the site points out, the tests “reads half a million locations in your autosomal DNA, giving you the most comprehensive, detailed picture of your ancestry that is commercially available. This means that 23andMe’s Ancestry tools provide you with more accurate, reliable data about your genetic similarity to populations across the globe.” Indeed, they will provide you with a Global Similarity Map and a Maternal Ancestry Tree, with the Paternal Ancestry Map soon to come.

For fellow genetic genealogists, 23andMe created a “fun facts about ancestry” page with a little bit of genetic genealogy trivia, and an extensive reading list. There is also an entire section which asks “Are Warren and Jimmy Buffett Related?” (I blogged about this interesting analysis back in May of this year).

The Ever-Present Ethical Concerns:

It is vital that a genetic-related company address the ethical concerns that will be shared by their customers and the public in general. 23andMe attempts to educate potential customers through a number of different means. First, there is a “considerations” page that lists and discusses many of the potential drawbacks and caveats associated with genomic sequencing. These concerns are further addressed in the consent documents which are presented to the customer before they can purchase the test.

There is also a “policy forum” which provides the company’s outlook on a number of controversial topics (including Direct-To-Consumer testing, Privacy, and GINA). As I am particularly interested in this area, I found this to be especially intriguing. There are also links for more information about these policy topics.

And from the NYT article, it appears that a customer is again presented with the many ‘considerations’ before they can access their information.

For More Information:

According to a press release at BusinessWire, there will be a webcast media briefing hosted by co-founders Linda Avey and Anne Wojcicki on Monday, November 19, 2007 at 2:00 pm EST. The link is here. I’ll be in class, so hopefully it will be available somewhere later in the day!

TechCrunch has a post “23andMe: Evil Or The Way Of The Future?” There’s a lot of discussion going on in the comment section.

Thomas Goetz, the author of the piece in Wired, wrote a post about the experience in his blog Epidemix (a fellow blog from The DNA Network). Mr. Goetz’s grandfather died at the age of 65 from heart disease, and as a result he hoped to learn more about his own risk – which, it turns out, is not evident in his DNA. The article is fantastic, and I highly recommend reading it (it also has a short video interview with Linda Avey and Anne Wojcicki). The last paragraph sums up some of my own feelings on the subject:

“…Wojcicki is onto something when she describes our genome as simply information. Already, we calibrate our health status in any number of ways, every day. We go to the drugstore and buy an HIV test or a pregnancy test. We take our blood pressure, track our cholesterol, count our calories. Our genome is now just one more metric at our disposal. It is one more factor revealed, an instrument suddenly within reach that can help us examine, and perhaps improve, our lives.”

I also recommend reading the New York Times article by Amy Harmon. Ms. Harmon had the opportunity to be one of the first to undergo 23andMe’s Personal Genome Service. Although she had many questions leading up to the test, by “three weeks later, I was already somewhat addicted to the daily communion with my genes.”

And finally, there is some discussion of the service among my fellow DNA Network bloggers, including My Biotech Life, On Genomics, and bbgm.