On that topic, Ryan Calo, a residential fellow at Stanford Law School’s Center for Internet & Society writes about a panel discussion held at the law school (pdf poster here):

“With a credit card and a saliva sample, consumers can now unlock the secrets carried in their DNA. Consumer genomics offers direct access to one’s genetic code, plus interpretations of health risks, family lineage, opportunities for social networking, and more. But how should consumer genomics be regulated? Join us for a panel discussion with leaders at the forefront of consumer genomics (23andme and Navigenics), media commentators (Alexis Madrigal from Wired), and policy makers.”

The moderator of the discussion was Hank Greely, a professor at Stanford whose work I highly respect and enjoy.

Calo writes in his blog that Navigenics has a strong statement in their privacy policy that they “will use reasonable and lawful efforts to limit the scope of any”  legally required disclosure, such as subpoenas and court orders.  During the talk, 23andMe co-founder Anne Wojcicki stated that 23andMe also has a policy to fight unreasonable requests for information (such as subpoenas).  Calo has more at his blog.

A recording of the panel discussion will be made available here at some point in the future.

Brendan Maher of Nature’s In the Field blog has more at “ASHG 2008: A stance, more or less, on genetic ancestry testing.”  Not much more covered here that was already written at The Spittoon - see “ASHG Releases Ancestry Testing Statement Emphasizing Interpretation.”

If you’re interested in seeing the Task Force’s webcast, it’s available here.

Let me start my analysis by clearly pointing out my personal positions:

• After years of experience in this field, I am a proponent of genetic genealogy testing, a scientific endeavor that has been utilized by as many as 500,000 to 800,000 customers.
• I believe that education, not more government regulation, is the most efficient and appropriate answer to the issues raised by the authors of the paper.
• I believe that autosomal genetic genealogy testing is in its infancy and should only be used with the understanding that the results are only extremely rough estimates that are subject to change as the field develops.

General Concerns:

With those personal positions in mind, and after reviewing the paper, I have a number of general concerns with the paper’s conclusions:

• There are statements in the paper about psychological reactions to testing results, including the conclusion that “[t]he occurrence of or potential for emotional distress in people and groups following receipt of conflicting information about their ancestry has been well documented.”  Unfortunately, the statements are based on anecdotal stories or isolated examples rather than any systematic or scientific investigation of the reactions of individuals to the results of genetic genealogy testing.  I am unaware of any systematic objective study that looks at the reactions of individual to genetic genealogy testing results (outside of the paternity test or health testing arenas).  Indeed, a prior policy paper from the ASHG cites only a BBC documentary that examined the ancestry of three individuals of African descent and a newspaper article to support their conclusion that “[t]est-takers may…suffer emotional distress if test results are unexpected or undesired.”  I would suggest that the Task Force, rather than assume that this “emotional distress” response to genetic genealogy test results has been well documented, conduct an objective study specifically tailored to analyze genetic genealogy testing. The difference between the results of genetic genealogy testing and the results of health or medical testing is so vast that drawing comparisons between the two is extremely problematic and potentially inaccurate.

• The paper muddles the distinction between Y-DNA/mtDNA testing and autosomal testing, even though the differences are huge.  The results of Y-DNA and mtDNA tests are STR numbers, SNP designations, or differences from the CRS which are then used to estimate a haplogroup or compare with another’s results.  Given the extensive data regarding haplogroup designation, the estimates are highly accurate.  Additionally, a haplogroup designation implies only a very broad geographical origin many thousands of years ago; it is not an estimation of genetic ancestry, as the authors of the policy paper imply.  Haplogroup designations have existed for more than 20 years and continue to be used by population geneticists and anthropologists.  The results of autosomal testing, however, are estimations of genetic ancestry.  These autosomal tests look at anywhere from 13 to 500,000 locations - out of billions - on the human genome and return percentages of ancestry based on those markers.  Autosomal testing can be confusing to test-takers because customer often assumes that the percentages are final and represent an accurate picture of their entire genome.

• The authors mix the issues associated with the everyday genetic genealogy test-taker with the issues faced by very specific groups of test-takers.  For example, Native American groups are concerned about the effects that genetic genealogy will have on group identity and membership.  These same concerns have also been raised by lineage societies such as the SAR and the Mayflower Society.  Any regulations that a group believes it needs should be at the level of the group, not at the level of the testing! Groups that have these concerns should themselves decide whether and how to use genetic genealogy results for membership and group identity (such as the DAR and Mayflower Society are doing); regulating genetic genealogy at the testing level is not the most efficient or appropriate way for these groups resolve the ethical and social concerns.

• There is mixing of the controversial phrase “direct-to-consumer” with genetic genealogy.  Of course it’s direct-to-consumer, who else would the results go to?  Surely the authors of the paper aren’t suggesting that genetic genealogy tests should be ordered and reviewed by a doctor or genetic counselor.  That would be a ridiculous restriction.

• Although I am unaware of the composition of the ASHG Task Force, I hope that it is made up of a diverse group. Additionally, I hope that the Task Force is actively conversing with people outside the committee, including commercial testing entities, researchers, and customers of genetic genealogy in order to obtain a well-rounded view of the field.

Specific Concerns:

Now, onto a few specific criticisms of the paper:

Limited Scope:

“Many people pursue genetic ancestry testing because they wish to find out more information about either the local populations or broad geographical regions in which their ancestors lived. However, the power of commercial genetic tests to answer such questions is limited, and the precision of the answer is often limited by the imprecision of the question. The limitations arise from the fact that every person has hundreds of ancestors going back even a few centuries and thousands of ancestors in just a millennium. There is thus enormous non-deterministic variation to the portion of the genome retained in a descendant from a given ancestor, with a rough expectation that it halves every generation. Consequently, genetic tests can access only a fraction of these ancestral contributions. The genomic segments contributed by a particular ancestor are far from all being uniquely identifiable, so even if one’s genome has those specific genome contributions, identification of particular ancestry is always uncertain and statistical. It is also unclear how well-inferred ancestry serves to predict the tested individual’s genotypes at untested loci.”

This paragraph largely deals with autosomal testing, but there is no clear distinction made.  The questions that can be answered by genetic genealogy depend on the type of testing that is done.  Additionally, there is no way to know for sure, short of testing, which ancestors contributed to your autosomal DNA (and even current testing is unable to do this, although it likely will be able to do so in the future).  However, it is clear who contributed your Y-DNA and/or mtDNA (your father’s father’s father’s father contributed your Y-DNA, for example, even if their names are unknown).

Accuracy:

“A major concern about the DTC ancestry testing business is that there is no quality assurance guarantee, and there is not even a mechanism to couple market performance with anything relating to accuracy. Cost pressures and market competition will likely drive costs down, and lower costs for ancestry testing services will probably be tolerated in this environment even if the accuracy suffers.”

I believe that the Task Force is aware of the GENEALOGY-DNA Mailing list, but I wonder if they are similarly aware that genetic genealogists often test the same markers with multiple companies. For example, test-takers were recently able to compare their results to the SNP results provided by new large-scale chip testing from 23andMe or deCODEme.  Similarly, test-takers have also compared the results of SNP testing by 23andMe and deCODEme and found that the results were almost identical (see here).  Many genetic genealogists, especially those associated with the GENEALOGY-DNA mailing list, are aware of and continue to explore accuracy issues. As a result, these individuals provide a market regulation mechanism that is much more robust that the authors imply, especially since some testing companies monitor and interact with these lists to address the concerns of customers.

Group Identity:

“For some groups (some Native American tribes, for example), a major concern about scientific efforts to explain origins is the apparent diminished regard for important cultural, religious, social, historical and political processes that also inform group origin, membership, and identity, and access to group rights. Some related issues include the use of genetic ancestry information as the basis for: changing one’s identity on various government forms; making claims to certain group rights or benefits; and immigration purposes, such as seeking dual citizenship.”

Since I already discussed this above, I won’t add much here.  Again I argue that any needed regulations should be established at the level of the group or organization rather than at the level of testing.  The government should establish guidelines about how to use DNA testing results when filling out identity on government forms, and groups should determine how to use DNA testing results when addressing group rights or benefits.  This is the most efficient and appropriate way to regulate these concerns.

Emotional Distress:

“Knowledge about genetic ancestry – if undesirable and unexpected – can elicit a range of psychological responses including shock, disbelief, denial, anxiety, anger, fear and other well-known reactions to unwanted news. It can also lead to the reshaping of individual or group identity. The occurrence of or potential for emotional distress in people and groups following receipt of conflicting information about their ancestry has been well documented.”

I discussed this concern above, but I wanted to raise one more issue.  While researching the ancestry of my great-grandmother, I discovered on a census return that she was ‘adopted’ as a child, and in fact I still don’t know the identity of her birth parents.  Finding this unexpected result in this document caused a number of emotional responses over the ensuing years, including some anger and frustration.  Should the government regulate access to census records, published family histories, or town records since finding unexpected results in these research sources can elicit emotional responses?  Should I have to use the services of a professional genealogy counselor to share the results of the research with me?  Based on my own anecdotal experience during 20+ years of traditional genealogy, I would argue that far more emotional distress is elicited by traditional genealogy than is elicited by genetic genealogy!  Note, however, that I claim this information is anecdotal, not “well-documented.”

Conclusion:

If nothing else, I hope that his policy paper incites thoughtful conversation about these issues.  I am genuinely interested in your thoughts and comments about both the paper and my response.  This is a very important time for genetic genealogy, and I encourage you to join the conversation by leaving a comment here at TGG.

And finally, in case you think that I am in complete disagreement with the paper, let me leave you with the group’s first recommendation which I consider to be sage advice:

“Because the science of ancestry determination has limitations, greater efforts are needed on the part of both industry and academia to make the limitations of ancestry estimation clearer to consumers, the scientific community, and the public at large. In turn, the public has the responsibility to avail themselves of information regarding ancestry testing and strive to better understand the implications and limitations of these assessments.”

“What is genetic ancestry and how does it relate to race and ethnicity? The development of increasingly cost effective genomic sequencing technologies and public interest in genetic ancestry has led to a dramatic flourishing of direct-to-consumer products and new approaches to biomedical research. In this session, panelists define the contours of this emerging landscape and explore the commercial, biomedical, social and ethical implications of this burgeoning category of genomic application. Panelists consider the following questions: What genetic ancestry information is available to consumers? How is genetic ancestry used in biomedical research? What implications do genetic approaches to ancestry have on social identity? What ethical and policy issues must be addressed in this changing landscape? Panelists provide perspectives from industry, medicine, cultural studies, and bioethics.”

The moderator of this session is Sandra Soo-Jin Lee of Stanford University.  The panelists include Joanna Mountain who will talk about ‘New dimensions for direct-to-consumer genetic ancestry testing’; Kimberly Tallbear who will talk about ‘The genetic construction of indigeneity’; and Esteban González Burchard who will talk about ‘The importance of ancestry testing and genetics in biomedical research’.  Additionally, the moderator will discuss ‘Racing forward: The ethics of ancestry testing.’

Comments:

I don’t like the mixing of the controversial phrase “direct-to-consumer” with genetic genealogy.  Of course it’s direct-to-consumer, who else would the results go to?  Should your doctor or genetic counselor review your genetic genealogy results?  That would be a ridiculous restriction.

The panelists will also be discussing the “ethical and policy issues” in this changing landscape.  As always, I believe that education, not more government regulation, is the answer to these ethical and policy issues.

The talk was a Syracuse Symposium event, and the first big event ever to be held in Syracuse University’s new $110 million Life Sciences Center.  I thought it was fitting that the first event to celebrate the future of the new life sciences building was a lecture that examined the collective genetic journey of mankind.

Dr. Wells began by giving the audience a very brief introduction about DNA and genetic genealogy.  He included a great quote that “The question of origin is actually a question about genealogy.”  For those that are not familiar with the Genographic Project, it was launched in 2005 and includes three primary missions:

1. Global DNA sampling from indigenous and traditional cultures which retain a geographic link with their current location;
2. Public participation; and
3. The legacy fund, which is funded by the public participation aspect of the project and aims to “empower indigenous and traditional peoples by supporting locally-led efforts.”

Dr. Wells is a great speaker and the hour-long lecture went by extremely quickly.  Some of the more interesting information he shared is not readily available on the Genographic Project’s website:

• According to current projections, the project is about halfway finished and is predicted to end in 2011.
• So far, 41,000 samples have been collected from indigenous populations, and 270,000 kits have been purchased by public participants in 130 countries (currently at about 800 kits ordered per week!).
• The indigenous DNA samples are stored for future analysis - this will undoubtedly be an irreplaceable asset as indigenous populations continue to decline (although it does raise issues of informed consent; do indigenous people really understand the information?).
• Eventually, the Genographic Project’s database will be searchable.

Valuable Research

He also highlighted the previous papers that resulted in party from the Genographic Project, including:

• The Genographic Project Public Participation Mitochondrial DNA Database
• The Dawn of Human Matrilineal Diversity
• Y-Chromosomal Diversity in Lebanon Is Structured by Recent Historical Events
• Identifying Genetic Traces of Historical Expansions: Phoenician Footprints in the Mediterranean

A new paper, soon to be released, will examine the genetic ancestry of the Toubou people indigenous to northern Chad in Saharan Africa.  The Toubou people have a rich and interesting history, but their actual genetic roots are unclear.  According to Sougoui, a Toubou:

“The Genographic Project is a great opportunity for us, the Toubou, because we are a people who are extremely interested in our origins… According to Toubou legend, we are a people who came from different places. This is a question that we continually talk about. We are anxiously waiting for the results of this study to answer this question for us. It is important for us as Toubou to know where we came from, how we got separated from other peoples, and how we actually fit into the world God created.”

Dr. Wells showed a short clip of a new documentary that is being made about the Genographic Project.  In the clip, we were shown the challenges of collecting DNA from the Toubou; looks like it will be another very interesting documentary.  See more about the Toubou project here and here.

The Q&A Session

During the Q&A session, someone asked what regions are missing from the database.  Perhaps unsurprisingly, the answer was the Americas and Australia.  Apparently the Project has had a very difficult time getting permission to take samples from these populations.

Many of the questions reflected the fact that many people are confused about the inheritance of Y-DNA and mtDNA.  Half the them were about whether a child or a sibling would have the same or different Y-DNA or mtDNA.

Conclusion

Dr. Wells is a great lecturer, and I highly recommend watching him speak if you are ever able to do so.  I learned a great deal about the Genographic Project, and I look forward to the information that will continue to be released from this valuable endeavor.

“As the number of human beings with their genomes fully sequenced ticks higher and direct-to-consumer gene profiling companies push the limits of what medical genetics can do, the once fantastical notion that any given human can walk into a doctor’s office with his or her genome on a hard drive looks more and more like a reality. Still the question remains to be answered: how do we use this wealth information? In this Nature web focus we proudly present the challenges this approaching reality poses for technology, the legal and ethical confines of research, and the ability of genomics to translate into clinical utility.”

Here are just a few of the interesting news & opinion articles:

• My genome. So what?
• How to get the most from a gene test
• Personal Genomes: When consent gets in the way
• Personal genomes: Misdirected precaution
• Personal genomes: The case of the missing heritability
• Personal genomes: A disruptive personality, disrupted

And unlike other bloggers who will undoubtedly mention these articles, I recommend that you read or peruse all the articles, not just the ones I happen to agree with!

In addition to the articles, Nature has a podcast (mp3) of special features on personal human genomes.  And lastly, follow along as Nature blogs from the 58th Annual Meeting of the American Society of Human Genetics in Philadelphia from November 11-15.  It looks like this is going to be quite a meeting.

HT: tweet from attilacsordas - are you tweeting yet?  Join me there.

Image via Wikipedia

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).

Image via Wikipedia

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!).