The Genetic Genealogist

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Ötzi the Iceman is the popular name for a 5,000 year-old mummy discovered frozen in the ice of the Alps in 1991.  Studies of the Iceman has revealed an immense amount of information about him, including details of his life, his death, and his culture. 

Although Ötzi’s mtDNA has previously been studied, researchers had only examined short segments which suggested that his mtDNA belonged to Haplogroup K.  A new paper in Current Biology (subscription only darn it) details Ötzi’s full mtDNA genome for the first time:

"Using a mixed sequencing procedure based on PCR amplification and 454 sequencing of pooled amplification products, we have retrieved the first complete mitochondrial-genome sequence of a prehistoric European. We have then compared it with 115 related extant lineages from mitochondrial haplogroup K. We found that the Iceman belonged to a branch of mitochondrial haplogroup K1 that has not yet been identified in modern European populations."

The full sequence (which has been deposited in GenBank with accession number EU810403) was then compared to 115 published full mtDNA Haplogroup K sequences.  The comparison suggests that Ötzi belonged to a previously uncharacterized subclade of Haplogroup K, now termed K1ö.

Strange Conclusions – Otzi has NO living relatives?

Now, as any genetic genealogist knows, when your mtDNA doesn’t match anyone you conclude that you have to wait until more people get tested.  This is especially true if you believe that your relatives would be in continental Europe – for some reason those continental Europeans have very little interest in genetic genealogy.  The authors point out that Ötzi’s mtDNA line might have died out in the past 5,000 years, but they also acknowledge that the comparison database was small and further testing in Europe might reveal more examples of this new subclade.

As Kambiz points out in the comments to his post on this new paper, the media isn’t quite as careful as the authors of the paper.  See "Iceman May Have No Living Relatives" by National Geographic, for example.  Although they do a decent job of discussing the article and all the aspects I mention, the title is so bad that it makes my teeth hurt.

Or Does he?

But see this article: "DNA shows Otzi the Iceman has kin."  According to the article, Alan Cooper – head of the University of Adelaide’s Australian Center for Ancient DNA – has also sequenced Otzi’s mtDNA and stated that "We have found someone very, very closely related."  I’m looking forward to comparing the mtDNA genome obtained by the two research groups.  Will they be the same?

A few points to remember:

• Ötzi’s mtDNA belongs to a previously undiscovered subclade of Haplogroup K, but there is currently no data to suggest that this subclade has died out in present-day humans.  115 mtDNA genomes barely constitutes a database!
• Remember that this is only mtDNA testing, which passes only from mother to child.  Even if there is no living person with mtDNA belonging to the K1ö subclade, Ötzi could still have 2 billion direct descendants!

The Paper:  Luca Ermini, Cristina Olivieri, Ermanno Rizzi, Giorgio Corti, Raoul Bonnal, Pedro Soares, Stefania Luciani, Isolina Marota, Gianluca De Bellis, Martin B. Richards, Franco Rollo (2008). “Complete Mitochondrial Genome Sequence of the Tyrolean Iceman” Current Biology, DOI: 10.1016/j.cub.2008.09.028.

HT: Anthropology.net.

Old 23andMe logo via CrunchBase

The latest issue of TIME Magazine lists the top 50 inventions of 2008, and the invention of the year is the Retail DNA Test.  The article is mostly about the product currently offered by 23andMe.  From the article:

“We are at the beginning of a personal-genomics revolution that will transform not only how we take care of ourselves but also what we mean by personal information. In the past, only élite researchers had access to their genetic fingerprints, but now personal genotyping is available to anyone who orders the service online and mails in a spit sample. Not everything about how this information will be used is clear yet — 23andMe has stirred up debate about issues ranging from how meaningful the results are to how to prevent genetic discrimination — but the curtain has been pulled back, and it can never be closed again. And so for pioneering retail genomics, 23andMe’s DNA-testing service is Time’s 2008 Invention of the Year.”

As the past year has shown, many people are opposed to this type of product for various reason, including that the test doesn’t involve genetic counseling, it isn’t ordered or interpreted by your personal doctor, and issues of genetic discrimination.  However, the article doesn’t shy away from these issues and provides a brief but interesting look into both sides.

This award highlights the fact that we are in the midst of a vast genetic revolution.  We are the first generation to be able to peer into the DNA inherited from thousands of previous generations.  Yes, the road will undoubtedly be bumpy, but I’m looking forward to the ride.  And so, I give my congratulations to 23andMe for this honor.

(Jim Watson via Wikipedia)

As if there wasn’t enough to worry about during the genetic revolution, researchers have found a way to characterize redacted genetic sequences from whole-genome or large-scale sequencing.

Here’s how it works.  Let’s say that Mr. X has had his genome sequenced, but doesn’t want to know the results of some genes known to influence the development or progression of Alzheimer’s Disease.  So when he receives his genomic sequencing, these genes have been ‘redacted’, or removed from the data.  This is exactly what James Watson decided to do when he received his data.

Characterizing Redacted Genes

However, researchers have characterized one of Watson’s redacted genes by examining the sequences surrounding the gene in question.  Often, when we inherit a gene from our patents, we receive that gene as well as some of the surrounding genetic sequence.  By examining the surrounding sequence, some insight into the redacted gene is gained.  For example, if I gave you the quote “A penny _____ is a penny earned”, you can derive from the surrounding words that the missing word is “saved.”

From an article discussing the researcher’s work:

“When the researchers told Watson about the paper’s results prior to publication, he redacted an additional 2 million DNA letters surrounding his APOE gene. This will make determining his redacted sequences much more difficult to decode – but not impossible, the authors write.”

Ethical Concerns

This ability, of course, raises numerous ethical concerns.  If we value the protection of privacy, even for people who make part of their genetic sequence available online, how do we protect their privacy?  Asking people to avoid this type of analysis won’t work, of course.  Is the only answer to redact huge portions of DNA surrounding redacted genes?  Or are we faced with an all-or-nothing question: either people put their entire sequence online (or just portions but face the risk of this analysis) or they keep their sequence private?

The authors of the study are also concerned about the potential problems.  From the paper:

“We believe the potential for such indirect estimation of genetic risk has considerable relevance to concerns about privacy, confidentiality, discriminatory and defamatory use of genetic data, and the complexities of informed consent for both research participants and their close genetic relatives in the era of personalized genomics.”

For more discussion, see the always-great Genetic Future.  See also “DNA detectives can decode ‘censored’ genomes” in New Scientist.

The article: Dale R Nyholt, Chang-En Yu, Peter M Visscher (2008). On Jim Watson’s APOE Status: Genetic Information is Hard to Hide. European J. of Human Genetics (DOI: 10.1038/ejhg.2008.198).

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This week I was quoted in the November issue of Wired Magazine about the use of autosomal DNA for genetic genealogy testing.

A Controversy

At “Adoptees use DNA to find surname,” Larry Moran at Sandwalk comments on my recent articles (here, here, and here) regarding the use of genetic genealogy (or genetic sequencing in general) test results to find unknown biological parents.  Although Dr. Moran accuses me of being a “cheerleader” who is blind to any ethical concerns associated with using DNA to find biological parents, he obviously didn’t do his research!  Less than a month ago I wrote this on the blog:

“For most people, being able to identify your own ancestors based on your own DNA poses few if any ethical dilemmas. However, what if your neighbor or your stalker or even law enforcement wants to use a sample of your DNA to identify your ancestors? Additionally, what if your living ancestor doesn’t wish to be identified? Does the ancestor have that right, or is possible identification through genetic genealogy just one of the consequences of parenting a child anonymously or simply having sex with another person?”

In response to a write-up at Genome Technology, Discovering Biology in a Digital World wrote “Hey sperm donors, could DNA testing be hazardous to your wealth?“.

Blending Genetic Genealogy and Personal Genomics

Often, articles that discuss both genetic genealogy and whole-genome scans (like those offered by deCODEme and 23andMe) blur the different services together and completely confuse the reader (usually because the author is confused!).  However, in “Will Technology Cure Health Care — Or Kill It?,” journalist Alistair Croll does a good job:

“Testing can get as low as $60, as Familybuilder recently showed. Founded in 2007, the company received a $1.5M Series A funding from DN Capital in February 2008. While the company only analyzes enough DNA to trace genealogy, it stores the raw samples for two years, so CEO Ilya Nikolayev hasn’t ruled out the possibility of selling additional analysis to customers in future.”

Russ Altman, a scientific advisor for 23andMe, recently wrote a blog post about his first “post-genomic moment.”  After reading an article about the possible association between a SNP and muscle breakdown due to statins, Altman logged into his 23andMe account and examined his read at that SNP.  There’s also a post about Altman’s experience at The Spittoon, 23andMe’s corporate blog.

The Personal Genome Project

The “First 10,” the first 10 participants in the Personal Genome Project, met on Monday the 20th to review the results of their genetic sequencing.  For more information, see a blog post by participant Misha Angrist, and Jason Bobe has a great round-up of articles at “Press coverage on the Personal Genome Project’s 2nd annual meeting at Harvard Medical School.”

Family Tree DNA Automates

Family Tree DNA is using new automated technology to manage their samples.  For more info, see “Family Tree DNA automates sample management” and “Geneology Testing Firm Adopts Tecan Sample-Management Systems” (but ignore the glaring spelling error!).

Image by gravitywave via Flickr

Last week I wrote about using genetic genealogy databases to identify someone’s surname (see “DNA Could Reveal Your Surname, Of Course.”)  The article discussed results from researcher Dr. Turi King which suggested that there is a 24% to 50% chance that two men who share the same surname share a common ancestor through that name, with chances increasing if the surname is rare.

Somehow I completely missed “Adoptees use DNA to find surname“, an article at BBC News this June.  Men who were adopted as children are using genetic genealogy databases in an attempt to identify their biological surname.  This is Dr. King’s research in motion.  Family Tree DNA, for example, has a project for Adopted people that is over 2 years old, and has a success rate of more than 30%, thanks in large part to their database of over 130,000 records.  From Bennett Greenspan:

“We now have a growing number of people who are adopted, who have tested with us and have matched several individuals with a particular surname, and maybe they haven’t matched anyone else with a different surname. From that, they can get the idea that they have at least found the surname they need to start looking for in the town in which they were born.”

The BBC article ends with Mark Jobling predicting what will happen in the future as technology opens doors for adopted individuals, stating that “tests offering better resolution on the whole genome should be able to solve other familial puzzles.”

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New research from Mark Jobling’s lab at the University of Leicester suggests that Y-DNA can be used to determine a male’s surname.

I know, I know, this is obvious to anyone who is familiar with genetic genealogy.  Just check out the many instances of this type of determination at ISOGG’s Success Stories website, for example.  However, as you’ll see below, this research has resulted in some new and interesting information.

Method

Dr. Turi King, who conducted the research, recruited over 2,500 men with roughly 500 different surnames to submit Y-DNA samples.  The sample set included a group not sharing surnames as well as sets of men (between 2 and 180) who shared a surname (including recognized variants).  She then typed 9 SNPs and 17 STRs.  There’s much more information about this research at the Jobling lab’s website regarding this project.

Results

Although this research may seem obvious, what makes it interesting are the actual statistics.  According to Dr. King’s research, there is a 24% chance that two men who share the same surname share a common ancestor through that name, and this increases to nearly 50% if the surname they share is rare. Keep in mind, of course, that this study was conducted solely in the U.K., so it is unclear how it applies to other countries.  From the press release:

“Dr King then went on to look at 40 surnames in depth by recruiting many different men all bearing the same surname, making sure that she excluded known relatives. Surnames such as Attenborough and Swindlehurst showed that over 70% of the men shared the same or near identical Y chromosome types whereas surnames such as Revis, Wadsworth and Jefferson show more than one group of men sharing common ancestry but unrelated to other groups.”

Implications

The implications of Dr. King’s research have strong significance for genetic genealogists, but the press release focused only on forensic science, stating that “the fact that such a strong link exists between surname and Y chromosome type has a potential use in forensic science, since it suggests that, given large databases of names and Y chromosome profiles, surname prediction from DNA alone may be feasible.”

For more analysis, see Anthropology.net.

I just finished reading an article by Alondra Nelson in the journal Social Studies of Science entitled “Bio Science: Genetic Genealogy Testing and the Pursuit of African Ancestry” (Social Studies of Science 2008 38: 759-783).  Dr. Nelson is Assistant Professor of Sociology, African American Studies and American Studies at Yale University.

This very interesting and insightful article aligns with my own premise, which I’ve stated previously, that receiving the results of a genetic genealogy test is only the beginning of the journey for any individual interested in their own identity or genealogy.

Based on her research in this area, Dr. Nelson writes about the complex interpretation of the results of genetic genealogy testing by African-Americans and black British.  Rather than completely altering their preconceived biographical narratives based on the results of testing, many people struggle to mesh genetic results with these narratives.  From the abstract:

“While there is some acquiescence to genetic thinking about ancestry, and by implication, ‘race’, among African-American and black British consumers of genetic genealogy testing, test-takers also adjudicate between sources of genealogical information and from these construct meaningful biographical narratives. Consumers engage in highly situated ‘objective’ and ‘affiliative’ self-fashioning, interpreting genetic test results in the context of their ‘genealogical aspirations’. I conclude that issues of site, scale, and subjectification must be attended to if scholars are to understand whether and to what extent social identities are being transformed by recent developments in genetic science.”

Nelson goes on to provide a deeper view into how some consumers of genetic genealogy “exercise some control over the interpretation of their test results” to formulate their own narrative “despite the presumption of [the tests'] conclusiveness”:

“My research shows that…the scientific data supplied through genetic genealogy are not always accepted as definitive proof of identity; test results are valuable to ‘root-seekers’ to the extent that they can be deployed in the construction of their individual and collective biographies. Root-seekers align bios (life) and bios (life narratives, life histories) in ways that are meaningful to them.  These users of genetic genealogy interpret and employ their test results in the context of personal experience and the historically shaped politics of identity. They actively draw together and evaluate many sources of genealogical information (genetic and otherwise) and from these weave their own ancestry narratives [footnotes and references omitted].”

I agree with Dr. Nelson’s assessment because I’ve seen it happen numerous times myself.  And, for at least two reasons, even the scientist in me finds support for why people might interpret their results personally: first, the results of a genetic genealogy test do not define me, since I am more than my DNA.  Second, genetic genealogy is still a young and rapidly developing field of science.

What do you think?  Should genetic genealogy consumers accept the results as definitive, or are they subject to personal interpretation?

“Genealogical Disorientation”

As part of the analysis, Dr. Nelson describes the effect testing can have on some individuals, in which “the receipt of genetic facts about ancestry open[] up new questions about identity and belonging, rather than settling them absolutely,”  and can create a “lack of orientation.”  She terms this effect “genealogical disorientation.”  I think this is a terrific term, and is undoubtedly one of the possible side-effects of genetic genealogy.

In fact, I have personally experienced my own genealogical disorientation, although it was minor compared to others.  My Y-DNA test revealed an anomaly found in only a tiny fraction of males – all of whom from England – and which had never been identified in Germany (where my ancestor was supposed to have originated).  This led me to wonder if there had been an NPE (non-paternal event) in my line and thus that my surname was possibly incorrect.  However, since I received my results others with nearby German origins have been shown to possess this particular anomaly, and thus my genealogical disorientation has subsided.

Where you disoriented when you first discovered your results?

Conclusions

So does the possibility of personal interpretation or genealogical disorientation mean that genetic genealogy is dangerous or unwarranted?  My answer to that question, perhaps unsurprisingly, is a resounding no.  It means that scientists, genetic genealogists, and testing companies must be aware of these possibilities and must continue to educate and support individuals who are interested in genetic genealogy testing.

The Personal Genome Project (PGP) was established to analyze and publicly share the genomes and personal information of up to 100,000 volunteers in order to advance understanding of “genetic and environmental contributions to human traits and to improve our ability to diagnose, treat, and prevent illness.”  In the first phase of the PGP, ten volunteers (the “First 10″ – see information about the First 10 here on my blog and at the PGP website) have had their DNA analyzed and have given their personal information.

Last month, George Church, the PGP’s principal investigator, reported that the project expected to publish data about the First 10 on its website in mid- to late October.  Church might have meant genotype (i.e. sequencing) information, since some information about phenotype, health history, and medication has already been posted on the PGP website.  There is information about each of the 10 participants, although there is currently no active link to their genetic information:

1. George Church
2. John Halamka
3. Esther Dyson
4. Misha Angrist
5. Kirk M. Maxey
6. Stan Lapidus
7. Keith Batchelder
8. Steven Pinker
9. Rosalynn Gill
10. James Sherley

Note that the First 10 are listed as “Participant #1″, “#2″, etc.  I debated about whether or not to attempt to identify them based on sex, ancestry, and date of birth, but since it was so simple to do that I decided to assign a name to the Participant number (I’m pretty sure I got them all right, depending on the quality of the source information I was able to find online).  Indeed, the PGP has clearly stated over and over that anonymity cannot be guaranteed for participants.  Additionally, I’ve always felt that one of the goals of the first phase of the PGP was to educate people about the effects of making your genomic sequencing information and health information freely available online.  Some would argue that the effects are completely or mostly dangerous, while others would argue that the effects are completely or mostly benign.  The PGP might help examine some of these questions.

There’s more information about the PGP in a recent Wired article.  HT: twitter from Jason Bobe of The Personal Genome.

Andrew Pollack at the New York Times wrote an article published today entitled “Dawn of Low-Price Mapping Could Broaden DNA Uses.”  The article is about a start-up company called Complete Genomics which will begin sequencing customer’s genomes for $5,000 starting in the second quarter of 2009.  From the article:

“Complete Genomics will not begin its service until the second quarter of next year. By then, the cost of competing technologies will no doubt have fallen further. Just last week, Applied Biosystems, a leading manufacturer, said it expected that its newest machine would allow a human genome to be sequenced for $10,000, although that includes only the cost of consumable materials, not labor or the machinery.”

The article next mentions Knome, which is still offering complete genomes for $350,000.  I expect that price to drop dramatically within the next few months.  Indeed, as the article points out:

“Complete Genomics will not offer a service to consumers. But it will provide sequencing for consumer-oriented companies like Knome.  Knome is already exploring farming out its sequencing to Complete Genomics. “We anticipate we’d be able to significantly drop our price,” said Jorge C. Conde, the chief executive of Knome, which is based in Cambridge, Mass.”

Interestingly, the company says that they are still making money at $5,000, and hopes to sequence a million genomes by 2013:

“Mr. Reid [the chief executive] said Complete Genomics hoped to perform 1,000 human genome sequences next year and 20,000 in 2010, with a goal of completing a million by 2013. That assumes the company can raise the money and find partners to build 10 sequencing centers at a cost of $50 million each. It also assumes there will be enough demand.”

Will there be enough demand?  What effect will this have on the cost of sequencing by other companies?  What effect will this have on the field of genetic genealogy?

Yesterday, RootsTelevision.com celebrated its two-year birthday.  RootsTelevision was created by Megan Smolenyak Smolenyak and Marcy Brown in 2006, and currently contains programs in 25 different channels!  You can read more about the site and about its creation at Megan’s Roots World.

You might remember that a few weeks ago I was interviewed by Dick Eastman for RootsTelevision.com, which was a terrific experience.  And don’t forget, you can stay up-to-date on RootsTelevision.com’s DNA Channel right here at The Genetic Genealogist!