The Genetic Genealogist

Last week I wrote about the results of my Family Finder autosomal DNA test by Family Tree DNA (see “A Review of Family Tree DNA’s Family Finder – Part I“).  The Family Finder test uses a whole-genome SNP scan to find stretches of DNA shared by two individuals, thus identifying your genetic cousins (and will soon include the Population Finder analysis of admixture percentages).  I currently have over 33 genetic cousins in Family Finder, and I’m working with them to identify our common ancestor(s).

The Affymetrix microarray chip used by FTDNA includes over 500,000 pairs of SNPs located on the X chromosome and the autosomes (no Y chromosome SNPs).  Via SNPedia:

FamilyTreeDNA uses an Affymetrix Axiom CEU microarray chip with 3,269 SNPs removed (563,800 SNPs reported) for autosomal and X (but not Y or mitochondrial) ancestry testing for $289. Other sources have cited 548011 snps. This platform tests 1871 of the 12442 snps in SNPedia.

FTDNA states that the Family Finder test is not intended to be medical.  From the FTDNA FAQ:

Question: Is the Family Finder test medical?

Answer: No, it is not.

This is entirely accurate of course; FTDNA does not analyze the test results for health, traits, or other medically-relevant information, and does not provide the user with any medical information or analysis tools that might reveal medical information.

However, when DNA is involved there is almost never any such thing as a completely non-medical test.  It’s often impossible, at any given point in time, to know which of an individual’s SNPs might be affiliated – remotely or closely – with a medical state or condition.  Ann Turner recently wrote the following at the Rootsweb GENEALOGY-DNA mailing list in response to another individual’s question:

Question:  “I am wondering if FTDNA really left out the genes and just lists the intergenic areas?”  Answer:  “No, the claim was that they scrubbed medically significant SNPs.  They still include over 1600 SNPs with entries in SNPedia, which would have some phenotype implications, according to an analysis posted at DNA-Forums: http://tinyurl.com/27slbj8.”

Indeed, as of August 3rd, 2010, there are 12,442 SNPs in SNPedia, of which a total of 1,871 are tested by Family Tree DNA’s Family Finder test.

Promethease Analysis

I was curious as to what information my Family Finder results might contain, so I ran my results through Promethease, a free software tool used to analyze whole-genome SNP scan results.  From the Promethease website:

“Promethease is a tool to build a report based on SNPedia [an impressive database of annotated SNPs] and a file of genotypes [i.e., your Family Finder results]. Customers of testing services (23andMe, deCODEme, Navigenics, …) can use it to learn more about their DNA. It can also pool the data from multiple testing services. The program runs for approximately 3 hours. An optional $2 payment per run unlocks extra features and reduces runtime to approximately 5 minutes.”

Similar to several of the other autosomal SNP scan testing companies, Family Tree DNA allows the customer to download their own DNA testing results.  Autosomal results and X-chromosome results are separately downloaded as compressed files which can then be extracted for analysis.  After downloading and installing Promethease, I ran the program using just my Family Finder results (after paying the $2 for a faster runtime.  I’m impatient.).

Promethease was  indeed able to analyze my Family Finder results and returned a report that included 1881 annotated genotypes. Here, for example, is a screenshot from my results (click to embiggen):

In addition to the “most interesting snps” category, there are categories for “medicines”, “medical conditions” (below), and others.  After clicking on “more” for each category, I receive more information about those annotated SNPs.  To get an idea of what the full results look like, there are a number of people who have shared their real promethease reports.

Promethease also lets you upload your results from different companies, so I also analyzed my Family Finder results together with the results of my 23andMe test.  Since there isn’t much overlap between the SNPs in the FTDNA test and the SNPs in the 23andMe test (see this ISOGG Wiki page for more information about FTDNA’s testing versus 23andMe’s testing, for example), I was able to extract information about 7691 of my personal genotypes using the SNPedia database (compared to 1881 genotypes with my Family Finder results alone).  Thus it appears that the 23andMe results are more likely to contain SNPs that are annotated in SNPedia.  This isn’t surprising considering that, according to reports, FTDNA designed their chip to contain fewer annotated SNPs.

My Results

Since I have taken whole-genome tests before and was familiar with both testing and the interpretation of results, my report was not surprising.  Indeed, I was already aware of my increased risk of type-2 diabetes (see Personalized Genomics: A Very Personal Post ), as well as the fact that I’m “probably light-skinned” (see e.g., my bathroom mirror).  However, it might not be clear to those taking these tests that the results contain a large amount of medically-relevant information.  This can be problematic when considering the fact that Family Finder test-takers might share or reveal their data with other people.  Indeed, even knowledge that you share a region of DNA with another person can reveal medically-relevant information that the two people share in that region.

On the other hand, this ability to apply Family Finder results to information in SNPedia will be of great interest to a number of test-takers who are interested in this type of genetic analysis.  This type of “do-it-yourself biology” is becoming more and more popular everyday.  Although there is still much debate regarding the utility of such information, exploring one’s genome can be highly interesting, informative, and interesting (and, to date, no one has adequately shown that exploring one’s genetic data is harmful for anything other than a tiny minority of people).

Conclusions

In conclusion, it is important for consumers to realize that ALL genomic information has the potential to reveal medically-relevant information (even Y-DNA and mtDNA results can include health information, for example).  By no means, however, am I suggesting that people should forgo whole-genome SNP scans, or that governmental regulation is needed.  Instead, I think it is vital that consumers understand the testing process and possible outcomes before testing, and I fully believe that it is the consumer, not the government, who should decided whether the consumer should or can undergo testing.

Indeed, rather than expend thousands of dollars in hearings, [faulty] investigations, and regulation, the government could use that money to fund programs that educate the population about genetics and DTC testing.  After all, we are entering a future that will involve our personal genomes in many aspects of our lives.

I’m interested to hear your thoughts on this subject, so please feel free to leave a comment below.

(Disclaimer: Please note that I received my Family Finder test without charge from Family Tree DNA for purposes of this review.  Regardless, I have attempted to review this product as honestly and as objectively as possible in order to provide valuable information about Family Finder to my readers.  I am also a consultant for Pathway Genomics.)

Doctor Radio

I was recently asked to participate in a discussion with Dr. Deb Neklason, Ph.D on the satellite radio channel “Doctor Radio,” hosted by Dr. Ira Breite.  We largely spoke about a 2008 study, led by Dr. Neklason (who I thought did a wonderful job of explaining the science and results in layman’s terms during the show), in which it was concluded that a gene that often causes cancer traces back to a Mr. and Mrs. George Fry who came to America in 1630.  I have a write-up of the study here (http://www.thegeneticgenealogist.com/2008/01/03/a-single-colon-cancer-gene-traced-to-1630-the-future-of-genetic-genealogy/).  There was also some brief discussion of mtDNA testing and the future of personal genomics.

Here is Dr. Breite’s description of this morning’s show:

“Colon Cancer is extremely common in the United States: it is the number two cancer killer of both men and women. Some families have a mutation which makes relatives who have it have an even higher risk than the general population. Now it turns out that this gene may have literally come over, if not with the Mayflower, then pretty darn close to that! Join me and Dr. Deb Neklason, Ph.D and Dr. Blaine Bettinger as we talk about how a single mutation in a single gene in a single person from 1630 has led to thousands of colon cancer cases today.”

For new visitors from the show looking for more information, feel free to browse the archives and featured articles here at The Genetic Genealogist.

Genomes Unzipped

I’m excited to announce the launch of a new personal genomics blog called “Genomes Unzipped.”  It’s authored by some of the best and brightest bloggers (and non-bloggers) in this area, including:

• Genetic Future‘s Daniel MacArthur
• Genomics Law Report‘s Dan Vorhaus
• Genetic Inference‘s Luke Jostins
• PHG Foundation‘s Caroline Wright and
• Saaien Tist‘s Jan Aerts, among others.

The blog (although it sounds like this will be much more than a blog!) promises the following:

Welcome to Genomes Unzipped, a new group blog bringing together experts in the scientific, legal, ethical and commercial aspects of genetics. Our goal is to provide you with independent analysis of advances in the field of genetics, with a particular focus on implications for the budding industry of personal genomics. We’ll also be discussing ways in which you can make the most of your own genetic data using online resources and techniques developed by researchers.

If you’re interested in genetic genealogy and/or personal genomics, I highly recommend subscribing to this blog (here) and their Twitter account (@genomesunzipped).  Also, look for a “major announcement” on the blog in the near future laying out some future plans for the group.

I wish everyone at Genomes Unzipped the best of luck, and I look forward to reading!

In a video available through CNBC, Linda Avey sits down to talk with Healthy Horizons about 23andMe.  The short video was originally aired today (7/24/09).

The newest entrant in the field of personal genomics has officially gone live.  Pathway Genomics, located in California, uses SNP testing to examine information about Health conditions, Ancestry, Carrier Status, Personal Traits, and Drug Response.  The company collects DNA via a spit kit, and has its own lab on-site:

We decided early on that the surest way to completely secure your information would be to build our own CLIA-certified laboratory. And that’s just what we did. Once we receive your saliva sample in our lab, your DNA never leaves the building. As a matter of fact, we place it in our proprietary DNA Lockbox for safekeeping. No other DNA testing firm offers this level of security. Others send your DNA elsewhere for testing, even to non-secure overseas locations!

The company has three levels of testing.  The first is the Ancestry Kit only:

The second level of testing is the Health Kit only:

And the third level of testing is both the Health and Ancestry Kit:

Ancestry Information

Not surprisingly, as a genetic genealogist, I am interested in the ancestry testing offered by Pathway.  The ancestry tests examines mtDNA in female customers, and both mtDNA and Y-DNA in male customers.  From the website:

Pathway Genomics hired some of the leading genetic genealogists in the world to design a custom analysis with the most precise and thorough genetic ancestry testing available.  Our maternal and paternal tests are 10 times more precise in their definition of haplogroups than other services, with more than 1000 maternal and over 200 paternal haplogroups.

This means that where other services will tell you that you are in Haplogroup J, we can tell you that you are in Haplogroup J2a1a – it is like the difference between saying you drive a Japanese car and saying you drive a 2009 Toyota Camry XLS.  By identifying your ancestry more precisely, Pathway Genomics helps you to identify people with whom you are more closely related.

Thus, Pathway Genomics uses SNP testing to identify customer’s mtDNA and Y-DNA haplogroups.  Because of the large number of genealogically-relevant SNPs tested, the haplogroup placement is very refined (see, for example, the ISOGG 2009 Y-DNA Haplogroup Tree, which is based on SNP testing).  The following graph emphasizes the difference in ancestry SNP testing by Pathway and ancestry SNP testing by other companies:

The Ancestry FAQ page has more information about ancestry testing.

Health Information

As the Health Kit above describes, the test examines SNPs related to more than 90 diseases, conditions, and traits, as well as carrier status of some genetic conditions, and drug interactions.  Lists of some of these conditions are here, here, and here.

Genetic Counselors

Pathway also has genetic counselors on staff for customers to ask questions and get more information:

In addition, because of the complexity and inherent uncertainties in genetic information, it is recommended that you discuss the results of your genetic test with a genetic professional, either a genetic counselor or a physician with specialty training in genetics. Our on-staff genetic counselors are available anytime.

General Information

Pathway has a blog called DNAction.  The company’s website also has information about the company’s Management and about their Science Team.  The Terms of Service and Privacy Policy, both of which I highly recommend any interested buyer read and study, are available online.  Testing is scheduled to take about 8 weeks according to the FAQ.

Testing Review

Stay tuned, I will be providing more information about Pathway Genomics, including a review of my testing experience, soon!

Disclosure

I am currently a consultant for Pathway Genomics.

Portfolio presents an interesting four-part series by David Ewing Duncan about personal genomics. But before I go on, it is important to realize that this series focuses on personal genomics – analysis of SNPs or sequencing throughout the genome – rather than the much narrower field of genetic genealogy. Although there are some ethical concerns surrounding genetic genealogy, they are not specifically addressed in the series.

Portfolio’s public relations coordinator circulated a summary of the series (I wish I had a PR coordinator!):

In Portfolio.com columnist David Ewing Duncan’s four-part series, “You 2.0,” he assess and compares three major websites recently launched that test a person’s DNA for risk-factors for everything from Alzheimer’s Disease and heart attack to drug addiction, an ability to taste bitterness, and ancestry. Is this information ready for prime time? Can it really predict a healthy person’s medical future? Duncan has been tested by 23andme, deCodeme, and Navigenics, and reports on his sometime contradictory and confusing, sometimes funny, and occasionally enlightening results gleaned from these controversial sites that are attempting to bring genetics directly to the people.

Here are the four parts:

1. You 2.0: Comparison Shopping For Your Future
2. You 2.0: I’m Doomed. Or Not.
3. You 2.0: Recreational DNA and Genetic Voyeurism
4. You 2.0: Closing the Genetic Gap

Look for David’s Book Later This Summer

According to his website, Duncan is writing a book entitled Experimental Man: One Man’s Intimate Journey Into Himself, Cell by Cell (although I’ve also seen it written as Experimental Man: A Molecular Autobiography) which is due to be available in late summer 2008. The book “describes and assesses a wide-range of leading-edge diagnostic tests that David has taken, from genes and environmental toxins inside him to brain scans assessing everything from his propensity to suffer from Alzheimer’s Disease to the politics of his brain. He is running these tests as an Everyman in an attempt to understand and humanize the often eye-glazing science that is about to change our world.” The Experimental Man Power Point Presentation is already available.

Sounds very interesting!

HT: The Gene Sherpa

For new readers of The Genetic Genealogist, 23andMe is a personal genomics company that offers a service to examine more than 600,000 SNPs throughout an individual’s genome. The information is then used to analyze ancestry (using Y-DNA and mtDNA) and to estimate propensity for disease. For much more info about 23andMe and similar companies, look under “Personal Genomics” on my Featured Articles page.

A Contest

Today, 23andMe announced on their blog – The Spittoon – the winner of the company’s first ‘Win Your Genome Contest’. The contest was to describe Lilly Mendel, a publicly available but anonymous profile at 23andMe – based upon her genetic information alone. The winner was Mike Cariaso, who previously created a program that analyzes 23andMe SNP data using the growing SNPedia database.

A New Partnership

In another announcement today, 23andMe released details of a partnership between the company and The Parkinson Institute to analyze the genomes of the Institute’s patients. Unlike the typical customer, the Institute’s patients will provide information about their “individual environmental exposures, family history, disease progression and treatment response.” The official press release is here, GenomeWeb News coverage is here, and there is a mention at Simon Lin’s blog Retail Genomics.

A Panel Discussion

Linda Avey, one of the founders of the company, recently participated in a panel discussion at the Cold Spring Harbor Biology of Genomes meeting. She was joined by representatives from two competitors, deCODEme and Navigenics. Daniel Macarthur at Genetic Future provides a fantastic and lengthy review and analysis of the discussion. A mention at Genome Technology Online laments the fact that the panel discussion was civil, even though it was a gathering of three competitors. The site also provides a summary of the meeting (subscription required).

A Controversy

Also in the news are reports that two states, California and New York, are evaluating whether personal genomics services offered by companies such as 23andMe and deCODEme are regulated by state laws, and if so, whether the companies are meeting those regulations. For more information, see “California, New York Officials Probing Gene-Testing Companies” at The Mercury News.

And Everything Else!

And lastly, here are a few newspaper articles or blog posts that mention the latest in personal genomics (note that these articles are provided so that you can perform your own analysis of personal genomic services – unfortunately, I haven’t evaluated these articles for accuracy):

• CBS News – Genetic Mapping More Hype Than Help?
• Wired Science – 23andMe: Certain About Uncertainty
• Washington Post – What’s in Your Genes? You Don’t Want to Know – Yet.
• redOrbit – Kinship is Rooted in Genetic Testing, Social Networking
• Forbes – I Want My DNA Test
• Reason – Does Genetic Testing Doom Private Insurance?

An article entitled “Gene Test Kits – Can They Lead To Dating Services” by Annalee Newitz discusses the author’s thoughts on the implications of genome sequencing offered by the number of companies that have sprung up in the past year. As a genetic genealogist who is interested in the intersection of law, science, and ethics, I’m always interested in articles that examine the ethical issues associated with affordable genome sequencing. Unfortunately, this article turned out to have little substance behind some serious accusations.

“Snake Oil”?

Newitz begins by mentioning companies 23andMe and deCODEme, both of which recently launched genome scanning services. She then proceeds to her thesis, which is that these services are not only not useful, they are dangerous. She states:

“While there are many theories about how genetic expression works on our personalities and health, there are few solid facts. Some tests, such as those for various kinds of developmental disabilities, have provable results. But many genetic tests, like those 23andme claim can reveal ‘athletic ability,’ are the biotech version of snake oil.”

Snake oil was used by the author to describe this product as having exaggerated marketing but questionable quality. If you do a search for ’23andMe and “athletic ability”‘, the second link is 23andMe’s “Variations: Speed Gene: Fact or Fiction?” which examines the proposed link between the ACTN3 gene and athletic ability. The mini-report cites the scientific study (Lucia et al. (2007). “Citius and longius (faster and longer) with no alpha-actinin-3 in skeletal muscles?” Br J Sports Med. 41(9): 616-7) behind the link and concludes in part with:

“The fact that this long jumper is the first and so far only Olympic power athlete to be found who lacks the “gene for speed” is evidence for how important this gene is in determining this type of athletic ability. But his success is a testament to the fact that genes are not destiny.”

The question of ‘exaggerated marketing’ or ‘questionable quality’ are debatable, as we’ve certainly seen in the blogosphere in the past year, so I won’t get into any further analysis other to say that these companies, much like genetic genealogy companies, apply the results of scientific studies to the customer’s DNA and are not simply making up the information. It’s important to remember that the people taking these tests are pioneers; they are amply warned that the results are not a diagnosis and shouldn’t be used to make any important life decisions. The average price of these tests, $1,000 to $2,500, also suggests that people will not buy them on a whim.

Eugenics?

My biggest concern comes from Newitz’s suggestion that genome scanning will lead to selective breeding (although she uses the term ‘eugenics’):

“But I don’t think it is just a little fun, like chocolate or “find the inner you” classes are. What I see when I look at a site like 23andme is nothing less than the future of eugenics. I don’t mean the scary capital E eugenics of the 1930s that involved killing Jews and sterilizing “loose women.” I mean wild-type eugenics, the kind of genetic engineering that happens in nature without any dictatorial intervention.”

“While newspaper stories about the new personalized genomics services trumpet the arrival of the future, I see nothing but the past. This isn’t science for the masses; it’s not enlightenment. It’s just the same old stuff dressed up in the language of modern biology and tricked out with a zoomy Javascript interface.”

I would argue that customers are using genomic services as a science and for their own enlightenment. For instance, just head over to the GENEALOGY-DNA archives and see all the discussion and analysis of the results of these products in the past 4 months. Genetic genealogists, most of whom are not phd-trained scientists (i.e. the masses), are already beginning to analyze the results of genomic sequencing for SNPs that might be associated with particular haplotypes, and thus reveal information about genetic genealogy. Although this represents just a fraction of the people who have been tested or are interested in testing, it suggests that people are interested in genome scanning as a scientific pursuit to learn more about themselves.

Newitz has an incredible resume (see Wikipedia), but after reading the article I was disappointed by her interpretation of the services offered by genome scanning companies. Although embracing very valid concerns about the cheap availability of genetic information, Newitz turned to sensationalism instead of an insightful discussion of the concerns. It’s possible that she chose to be a little controversial for the purpose of interesting journalism, but I feel like the sensationalism took away any value from the discussion. I’m certainly not discounting any of Ms. Newitz’s concerns, I just wish the article had shared more information in order to produce more informed readers.

Megan Smolenyak Smolenyak, one of the founders of Roots Television and the author of Megan’s Roots World recently released a screencast of her husband’s deCODEme results at “A First Look at deCODEme DNA Results.” Megan is the Chief Family Historian of Ancestry.com and is co-author of Trace Your Roots With DNA, and thus is both extremely interested in genetic genealogy and aware of the limitations of this type of DNA analysis. The 17-minute review includes a brief look into the different aspects of deCODEme’s analysis, including health and ancestral information.

That’s the title of an article at BBC News yesterday. The article’s header states that:

“More and more people in the UK are following America’s lead in spending hundreds of pounds on private genetic tests.”

The article is about genetic testing for health concerns, not for genealogical purposes. Although the article is very short, the author does manage to highlight a few of the potential benefits and downfalls of genetic testing.