The Genetic Genealogist

On April 9th, 2008, I posted a quiz about genetic genealogy here on the blog. (If you haven’t taken the quiz yet, it is available here; it only requires a few minutes and might make the following analysis more clear and personally relevant). I created and posted this quiz because I thought it was a fun way to interact with my readers, and because I thought it was educational material to share with others.

As readers began to take the quiz, I realized that there was valuable information contained with the results. The following is an analysis of those results with a few preliminary conclusions. As I proceed, don’t feel bad about missing any of these questions, since this isn’t meant to be a critique of any single individual (especially since individual responses were not recorded). I merely hope to share the results as a whole in an effort to help inform and educate. The quiz was, and still is, meant to be fun.

Additionally, this analysis is also not meant to be a negative critique of genetic genealogy. There are MANY benefits to genetic genealogy testing, when it is used correctly. It can break (and has, many times, broken) through brick walls, validate traditional genealogical research, and confirm or deny a genetic relationship between two individuals in a relevant genealogical timeframe. As one of the correct answers in the quiz stated, genetic genealogy “is the forefront of science, and I get to play along.”

Results
As of today, the quiz has been completed a total of 375 times. Most of the questions were easily answered, ranging from 80% correctly answered (“We all came from Africa, so why bother with a genetic genealogy test?” – Correct answer: Many things have happened in the last 100,000 years) to 97% correctly answered (“Genetic genealogy is a scam, created by big business to capitalize on consumer ignorance” – Correct answer: False). For some of these, the incorrect answers were probably a result of the ‘fun’ element I added to the quiz, such as creative (but less-correct) answers. Each question, however, had an answer that I considered to be the “best” answer.

Prior Research Required?
Only two of the questions had correct answer rates below 80%, and perhaps not surprisingly the questions were directly related. The most problematic question in the quiz, with a correct answer rate of just 46%, was the following: “I can sign up for a genetic genealogy test without doing any prior research.” The answers were:

• A1. True – heck, I’ve been doing genealogy for years.
• A2. True – after all, I saw it on TV.
• A3. False – no way! (correct)
• A4. Why would I have to research genetic genealogy?

Although the service I used did not track which answers were selected, I have a feeling that many individuals chose “A1″ rather than the correct answer of “A3″, under the assumption that experience with genealogy prepares an individual for genetic genealogy. However, the fact that a genealogist has been doing research for years does not mean that they should undergo genetic testing without prior research. The other incorrect answers, “A2″ and “A4″ are also problematic in that they suggest that either (1) TV reporting/coverage provides enough background information to fully inform an individual about genetic testing, or (2) that no research is needed for genetic genealogy.

Health Information Revealed?
The need for research before genetic testing is evident from the second-most frequently missed question, with 26% answering incorrectly, which states: “The results of a genetic genealogy test might reveal health information about me.” The answers were:

• A1. True! (correct)
• A2. False!
• A3. My DNA knows exactly how much I weigh.
• A4. Genetics has nothing to do with my health information.

Again, I am uncertain which incorrect answers were chosen, but “A2″ and “A4″ are essentially the same answer and suggest that there is no connection between a genetic genealogy test and genetic disease or health. “A3″ is one of the ‘other’ elements I mentioned in the introduction (and my sorry attempt at humor!).

A total of 1 out of 4 individuals was unaware that a genetic genealogy test can reveal medical information. I have previously highlighted this problem here at TGG, and I included it in both my eBooks (see the sidebar). Many people are unaware, for example, that a Y-DNA test, provided by some of the major genetic genealogy testing firms, can reveal male sterility. Additionally, a full mtDNA sequence can reveal any one of a number of metabolic or other genetic disorders. Although the percentage of these results is extremely low and I don’t think this should discourage people from genetic genealogy, I do believe that people MUST be aware of the possibilities BEFORE swabbing their cheeks.

Conclusions
Today I received the following comment: “This quiz fails to distinguish between facts – you can get a test done without doing any research – and values – you should do some research first. Poor.” I have to admit that receiving this comment stung a little, but then I realized that the author of this comment served to perfectly reinforce the results of the quiz. A genetic genealogy test is a genetic test. Although it is not meant to detect genetic disease or reveal other secrets contained within the genome (such as adoption and illegitimacy), it is fully capable of doing so. As with ANY type of genetic testing, the tested individual must be aware of the possible outcomes before consenting to the test. Educating individuals about the possible outcomes of genetic genealogy is just one of the goals of the Genetic Genealogist. I have a feeling that my regular readers were among those that answered these difficult questions correctly.

Thank you to everyone who took the quiz or wrote about it on their blog or newsletter. I hope you enjoyed taking it, and I hope you’ll consider taking future quizzes. To stay up-to-date on the latest in news and information about genetic genealogy and personal genomics, subscribe to my feed.

Around the year 1700, a relatively healthy young hunter was walking along a glacier in land that would one day be British Columbia in Canada. He wore a robe of 95 animal skins, perhaps gopher or squirrel, stitched together with sinew, and carried a walking stick, iron-blade knife, and spear thrower. For some reason, the young man, aged 17 to 22, died on the glacier and was quickly incorporated into the ice. There he remained, frozen, for the next 300 years.

In August 1999, three hikers noticed a walking stick, fur, and bone lying on a melting glacier (60′ N 138′ W). The young hunter, renamed Kwäday Dän Ts’ìnchi in the Southern Tutchone language of the Champagne and Aishihik First Nations, was removed by scientists for analysis (see the NY Times article, and the Journal of Canadian Archaeology article). From an article in the Sydney Morning Herald:

[When scientists were led to the site], they found a torso with the left arm attached. The hand was mummified. The fingernails were missing. The head was missing, too. A few metres away lay the lower body, with thighs and muscle attached. They also found a wooden dart and walking stick, and pieces of fish and scales within the folds of the man’s robe.

Over the next two days the team members carefully lifted the remains. They collected a knife still in its sheath and a leather pouch. They found a woven hat, fragments of clothing and what was later described as the man’s “personal medicine bag”, which was considered sacred, even after more than five centuries. They did not open it.

In 2001, Kwäday Dän Ts’ìnchi’s remains were given back to the Champagne and Aishihik, and in July 2001 he was cremated in a closed ceremony and returned to the glacier. Kwäday Dän Ts’ìnchi’s skull was found in 2003 but was not removed from the site.

Discovery Continues

Even though Kwäday Dän Ts’ìnchi has been cremated, the analysis of his DNA, intestinal contents, and artifacts continues. This past weekend, at the Kwäday Dän Ts’ìnchi Symposium, researchers around the world presented the results of their research:

The conference brings together more than 30 researchers from fields as diverse as archeology, criminology and microbiology. They come from local universities, the Royal B.C. Museum, Vancouver General Hospital, first nations, and institutions as far afield as Indiana and Scotland.

Haplogroup A

One of the research projects involved sequencing of Kwäday Dän Ts’ìnchi’s mtDNA, which revealed that it belonged to Haplogroup A, with the polymorphisms 16111T, 16189C, 16223T, 16290T, 16319A, and 16362C. As part of the study, the researchers collected blood samples from 250 to 300 members of the Champagne and Aishihik First Nations to compare their mtDNA sequence to that of Kwäday Dän Ts’ìnchi’s (more info here and here). At the Symposium, the researchers revealed that 17 people had mtDNA that closely matched that of the subject, suggesting that they are close maternal relatives. 15 of those 17 people belong to the Wolf clan, also suggesting that Kwäday Dän Ts’ìnchi might have belonged to the Wolf clan himself (more info here).

This topic is of particular interest to me, since my mtDNA belongs to Haplogroup A and therefore I am also (very) distantly related to Kwäday Dän Ts’ìnchi. Last year I profiled the Qilakitsoq mummies in Greenland, all of whom belonged to Haplogroup A.

HT: Geneasofts

Megan Smolenyak Smolenyak recently wrote “I’m a Euro-Mutt!” about the results of her AncestrybyDNA EuropeanDNA 2.0 test (from DNAPrint Genomics). Megan found that the results of her test were both expected and surprising! From DNAPrint Genomics’ website:

DNAPrint® Genomics’ powerful new EuropeanDNA 2.0 product, further elucidates European sub-ancestry using 1,349 European Ancestry Informative Markers (SNP AIMs). This test reports a customer’s proportional basic continental European ancestry: Southeastern Europe (SEE – Armenian, Jewish, Italian and Greek), Iberian (IB -Spanish, Portuguese), Basque (BAS – Spanish/French Pyrenees border), Continental European (CE – German, Irish, English, Netherlands, French, Swiss and some Italian) and North Eastern European (NEE – Polish, Baltic, Swedish, Norwegian, Finnish, Russian) ancestry.

For the newbies, this test examines autosomal DNA, which is DNA other than the sex chromosomes and mtDNA. These types of tests will become much more popular as SNP testing and genomic sequencing become cheaper and more widespread.

Roots Television

Have you visited Roots Television lately? Don’t forget that the DNA Channel is available here at TGG (click the Roots Television – DNA Channel button above). Currently featured (under “DNA Testing”) is an interview with Rick Kittles, the co-founder of African Ancestry and a well-known name in the genetic genealogy field.

Yesterday, a very interesting paper was published in the American Journal of Human Genetics by the Genographic Project Consortium entitled “The Dawn of Human Matrilineal Diversity.” The results of the study, which examined the 624 mtDNA genomes from sub-saharan Haplogroup L lineages, suggests that humanity once split into two small groups with one group in eastern Africa and the other in southern Africa, and that humanity bottlenecked into a relatively small number of individuals (as few as 2,000 based on results from a previous study). Note, as always, that these are hypotheses based upon the results of this and other studies, and will require further research to support or refute.

Two mtDNA Branches

The human mtDNA tree has two main branches, the L0 branch which includes individuals concentrated in southern and eastern Africa, and the L1’2’3’4’5’6′ branch (aka the L1’5 branch), which includes the entire remainder of humanity including non-Africans (see the figure to the left). Based upon the analysis of the 624 genomes, the researchers hypothesized that the L0 and L1’5 branches diverged into two small populations around 140,000 to 210,000 years ago, with one group settling in eastern Africa (the L1’5 branch) and the other settling in southern Africa (the L0 branch). Interestingly, the results also suggest that there was little to no intermingling of these branches for the next 50,000 to 100,000 years!

The L0 branch comprises 60% of the Khoisan people (two ethnic groups named the Khoi and the San) of Southern Africa. The L1’5 branch comprises all other branches of the mtDNA tree, which includes the N and M matrilines that eventually spread out from Africa.

Population Bottleneck

The results of the study also suggest that humanity was once comprised of a relatively small number of individuals (as few as 2,000, according to another study cited by the researchers). This was suggested because there are very few matrilineal lineages present today that split during the first 100,000 years of our species’ history, likely because they they died out or never developed in the first place. If there had been many more individuals alive at that time (with descendants alive today), scientists would expect to see more different types of lineages in Africa. This is what happened during the second 100,000 years of human history, with as many as 40 different matrilines at the time that humans left Africa to spread to the remainder of the world. As many of us know now, there is a multitude of current matrilines because of our enormous population explosion in the past few thousand years. Note, however, that this hypothesis may change if researchers suddenly discover large amounts of new matrilines present in Africa which split from the main line in the first 100,000 years.

An article in the Economist did a very good job of making the article understandable. Here is a quote from this terrific article in the Economist, which I suggest you read for yourself:

Comparing Khoi and San DNA with that of other Africans shows that the first big split in Homo sapiens happened shortly after the species emerged, 200,000 years ago. Most people now alive are on one side of that split. Most bushmen are on the other. The consortium’s analysis of which DNA “matrilines” are found where suggests that for much of its history the species was divided into two isolated populations, one in eastern Africa and one in the south of the continent, that were defined by this split. However, few other matrilineal splits from the first 100,000 years of the species’s history have survived to the present day.

This suggests the early human population was tiny (so the opportunities for new matrilines to evolve in the first place were limited) and reinforces the idea that Homo sapiens may have come close to extinction (eliminating some matrilines that did previously exist). Indeed, there may, at one point, have been as few as 2,000 people left to carry humanity forward.

This shrinkage coincides with a period of prolonged drought in eastern Africa, and was probably caused by it. The end of the drought, however, was followed by the appearance of many new matrilines that survive to the present day. The researchers estimate that by 60,000-70,000 years ago, the period when the exodus that populated the rest of the world happened, as many as 40 such groups were flourishing in Africa—though that migration involved only two of these groups.

For more information, check out the following sources:

• National Geographic – After Near Extinction, Humans Split Into Isolated Bands
• The Associated Press – Study says near extinction threatened people
• CNN – Humans nearly wiped out 70,000 years ago, study says
• Sydney Morning Herald – Dry spell almost killed off race
• Scottsman – How climate sent humans to the edge of extinction
• BBC News – Human line ‘nearly split in two’

1:25PM EST: Senator Olympia Snowe is currently on the floor of the Senate speaking about GINA (see it live on C-SPAN 2). And yes, I realize that live-blogging C-SPAN coverage is dangerously boring, but I can’t help myself!

3:00PM EST: I just received a press release from the Genetics & Public Policy Center that GINA passed the Senate 95-0:

The Senate today passed the Genetic Information Nondiscrimination Act (GINA), approving by unanimous consent of 95-0 an amended version of H.R. 493, which passed the House April 25, 2007 by a vote of 420-3. The House is expected to take up the measure again quickly before sending it to President Bush to sign the measure into law.

“After a very long wait, Americans can now be confident that their genetic information cannot be used by health insurers or employers in harmful or hurtful ways,” says Kathy Hudson, director of the Genetics and Public Policy Center, established at Johns Hopkins University by The Pew Charitable Trusts. “Our challenge now is to make sure that doctors and patients are aware of these new protections so that fear of discrimination never again stands in the way of a decision to take a genetic test that could save a life.”

The legislation, when signed, will fulfill the longstanding agreement among American citizens and politicians that protection from genetic discrimination should be clear and consistent, Hudson explains. Until now, individuals’ genetic information has been protected only by a largely untested patchwork of state and federal regulations. Ninety-two percent of Americans are concerned that results of a genetic test could be used in ways that are harmful to the person.

Moreover, scientists can now in good conscience tell patients and research participants that their genetic information is protected against misuse by health insurers and employers. Linking gene variants to health outcomes often requires studies involving large numbers of people, but scientists report that potential subjects are deterred by the fear that their information could be used against them by employers or insurers. In a survey of more than 4000 people conducted earlier this year, for example, the Center found that when considering whether or not to participate in genetics research, 93 percent of respondents said it was important that it be “illegal for insurers or employers to get my information.”

In addition to impeding research that would help to bring about the much-heralded era of personalized medicine, the threat of discrimination affects individual patients who could benefit from genetic testing have sometimes foregone it out of concern over possible repercussions. When people opt not to be tested, they lose the opportunity to seek monitoring and preventive care to avoid conditions for which they are at higher risk. Passage of GINA means that Americans will no longer have to make the trade-off between genetic privacy and appropriate health care.

The Senate unanimously passed versions of GINA in 2003 and 2005, but in both years the bill stalled in committee in the House. Last year, however, the House passed the measure quickly and today, the Senate for a third time expressed its commitment to nondiscrimination.

On April 27, 2007, I wrote “GINA: A Primer“, which was an introduction to the Genetic Nondiscrimination Act. Today, nearly a year later, the bill will most likely be voted on and passed by the Senate, the last step before being handed over to President Bush to sign into law (which he has indicated that he will do). As I wrote last April:

“GINA aims to protect individuals in a variety of different areas. The legislation would prohibit access to genetic information by insurance companies and would prohibit insurance companies from discriminating against an applicant based on genetic information, the refusal to submit genetic information, or for have been genetically tested in the past. Additionally, the Act would prohibit employers from using or collecting genetic information to make employment decisions. The Act also establishes a Genetic Nondiscrimination Study Commission that is charged with reviewing new developments in the field of genetics and advising Congress.”

This bill is considered by many to be an important first step in providing protections against the misuse of recent and future developments in genetic sequencing and analysis technology.

There is a great deal of information about today’s vote:

• The New York Times – Congress Near Deal on Genetic Test Bias Bill
• The Gene Sherpa – GINA will PASS! Thanks GTO!
• American Society of Human Genetics – Genetic Scientists Anticipate U.S. Senate Passage of GINA (pdf)
• CNN – Lawmakers back bill to ban genetic discrimination at work
• GenomeWeb Daily News – Senate to Vote on GINA Tomorrow … Finally
• Eye on DNA – GINA Nears Unanimous Consent Passage in U.S. Senate
• Women’s Bioethics Project – Genetic nondiscrimination bill finally coming up for Senate vote
• Genomeboy.com – A momentous hump day

There is also some very recent information from the Center for American Progress entitled “Genetic Nondiscrimination: Policy Considerations in the Age of Genetic Medicine” (full pdf report here).  The Center (which I am not familiar with) also has a recent interview with a genetic counselor: “It’s All in the Genes (Or Is It?)”

Stay tuned!

The Washington Post has an article entitled “From DNA of Family, a Tool to Make Arrests” about using DNA obtained from family members to search DNA databases or identify relatives as criminals. Here is a summary of the issue from a recent Columbia Law review article available here (pdf):

For years, law enforcement personnel have compared DNA found at crime scenes with that of a convicted offender. Recently, a new technique has
begun to focus on the genetic similarity of biological relatives. Now, if a crime scene sample partially matches the DNA profile of a previous offender, law enforcement can investigate and possibly arrest that person’s family members. This process is called familial DNA testing and will significantly increase the amount of genetic information contained in the FBI’s Combined DNA Index System (CODIS), which consolidates local, state, and federal DNA databanks into a uniform body of data.

Hank T. Greely, a law professor at Stanford, is mentioned late in the article. Mr. Greely is an expert on this topic and has written a number of articles including “Family Ties: The Use of DNA Offender Databases to Catch Offenders’ Kin” (34 J.L. Med. & Ethics 248, 250–51 (2006)). Mr. Greely has argued, as have others, that this type of testing will disproportionately affect minorities such as African Americans because every year “more than 40 percent of people convicted of felonies in the United States are African American.” As Greely points out in the Washington Post article:

“If the national database were used for familial searching, he said, and assuming that on average each person whose profile in the database has five first-degree relatives, authorities would be “putting under surveillance” roughly a third of the African American population, compared with about 7.5 percent of the European American population, he said.”

Genetic Genealogy Testing on Suspect DNA

At the current stage of technology, comparing the results of a genetic genealogy test using DNA obtained from a suspected criminal to public databases such as Y-search or mitosearch would be of limited value. There is a remote possibility that an exact match might be found (as so many of us that are searching for exact matches can attest to), but it is unclear how useful that information would be, or if it would even be admissible evidence in a trial. With user-annotated data in most public databases, there is little direct or reliable evidence that any DNA sequence is actually associated with a user or a surname. This is, of course, a problem that even hobbyist genetic genealogists face with public databases.

It should be noted, however, that autosomal genetic genealogy has already been adopted for use in criminal investigations. DNAPrint Genomics offers DNAWitness, a product that offers autosomal analysis similar to their Ancestry by DNA service. From two recent press releases about DNAWitness (pdf):

DNAWitness™ derives the percentage of European, East Asian, Native American, and Sub- Saharan African markers in a person’s DNA. This ratio for an individual is termed BioGeographical Ancestry (BGA), representing general characteristics that can be matched with a searchable database containing information and photographs collected from samples around the world, leading to more accurate identifications of potential of criminal suspects.

Law enforcement officers use DNAWitnessâ„¢ 2.5 to determine genetic ancestry from DNA samples obtained from crime scenes, narrowing the potential suspect pool to a more focused group of likely candidates. The test enables law enforcement agencies to reduce both the cost and time needed to apprehend suspects. Current forensic DNA products in the market act like a fingerprint and can only be used to match DNA specimens.

The Future

As sequencing becomes cheaper and the complexities of the genome are more completely understood, the future of using DNA samples from crimes scenes will likely be very different. In addition to comparing DNA to sample databases, officials might be able to estimate the suspect’s height, weight, hair color, skin color, eye color, handedness, age, and so forth. It will be interesting to see what the future holds.

HT: M.E.B.

Yesterday the Spring 2008 Issue of the Journal of Genetic Genealogy was published online. As always, the journal and every article is completely FREE. Here is a listing of the articles in the current issue:

• Editor’s Corner – A New Y Tree by Whit Athey
• ‘Satiable Curiosity – Y-Chromosome and mtDNA Information from deCODEMe by Ann Turner
• Genetic Structure of an Isolated Sub-Tribe of the Adi People of Arunachal Pradesh State in Northeast India: Isonymy Analysis and Selective Neutrality of Surname Distribution in Adi Panggi by Suvendu Maji and T. S. Vasulu
• The Subclades of mtDNA Haplogroup J and Proposed Motifs for Assigning Control-Region Sequences into these Clades by Jim Logan
• A New Subclade of Y Haplogroup J2b by T. Whit Athey and Bonnie E. Schrack
• Where Did European Men Come From by Kalevi Wiik

In January I wrote about a study that traced a mutation in a single colon cancer gene to 1630. Today, researchers announced that a founder mutation in another gene, MSH2, has been traced to roughly 500 years ago (“Origins and Prevalence of the American Founder Mutation of MSH2” (pdf)).

MSH2 is a mismatch repair gene, and mutations in the gene results in Lynch syndrome, also known as hereditary nonpolypsis colorectal cancer. Lynch syndrome accounts for 2.8% of all colon cancers in the Western world, with 4,500 cases a year in the U.S. One specific mutation in MSH2, the deletion of exons 1 through 6, was named the American Founder Mutation (AFM) and was identified in nine families. Previously, research had suggested that the mutation in the MSH2 gene had been brought to Pennsylvania by German immigrants in the early 1700’s.

AFM More Prevalent Than Previously Thought

Upon further examination, researchers identified 32 new families who carried the AFM. Using extensive genealogical research that tracked the families as far back as the 18th century, 27 of the 41 AFM families were coalesced into seven extended pedigrees. These pedigrees are all available as WorldConnect databases. Unfortunately, the identification of 32 new families suggests that Lynch syndrome is far more prevalent than previously thought.

The AFM Arose About 500 Years Ago

Software used by the researchers predicted that this mutation arose about 500 years ago (with a 95% confidence interval of 425 to 625 years ago). Given that the seven extended pedigrees each had a common ancestor born between 1700 and the early 1800s, the researchers concluded that it was unlikely that there was a single common ancestor who arrived in the United States to link all the families. As a result, two hypotheses were asserted: either the AFM began with a common ancestor in Europe before the families emigrated to the New World, or, in light of the age of the mutation, it arose in a Native American population. Notably, despite efforts by the researchers, the specific MSH2 AFM has not yet been identified in Europe.

Genetic Genealogy Not Just for Entertainment

This study is another example of researchers using genetics and extensive genealogy research to identify the origins of disease-causing mutations. These studies do more than just attempt to identify a founder, which might be considered just entertainment. Rather, this research identifies genetic relatives who might be candidates for genetic screening and allows scientists to estimate the prevalence of certain mutations. Additionally, this study in particular identified three states (Ohio, Kentucky, and Texas) where the AFM is more prevalent. Luckily, there are some measures that affected individuals can take to minimize the danger of the AFM.

For More Information:

ThinkGene – Inherited cancer mutation is widespread in America

The Columbus Dispatch – Study retraces colon-cancer link

I recently received notification that The Genetic Genealogist has been rated a 9.0 at Blogged:

What is Blogged? From the website:

“Blogged.com is all about blog discovery. It’s a place for readers to discover interesting blogs and for authors to discover who their readers are. Blogged goes beyond being a traditional blog directory. We focus on providing tools for bloggers and readers alike. Through our database of over 200,000 blogs, readers can discover and explore new blogs. Through our user community, blog authors and their readers can communicate and interact directly with each other. Our blogs are reviewed, rated, and categorized by our editors, so you won’t have to experience the frustration of filtering through blogs that are either spam, outdated, or irrelevant. You’ll be able to find quality blogs that you would have unlikely found through a traditional blog search.”