The Genetic Genealogist

Today at 1:15PM, the American Society of Human Genetics released the “ASHG Ancestry Testing Statement and Recommendations (pdf)” during a press briefing session entitled “ASHG Ancestry Testing Statement and Recommendations: Guidelines for Understanding the Issues and Implications Involved.”  The briefing session, held from 1:15PM to 2:15PM, is part of the 58th annual ASHG meeting in Philadelphia.  The paper was drafted by the recently-appointed ASHG Ancestry Testing Task Force Committee.

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.”

(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 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.”