The Genetic Genealogist

This weekend I wrote about an article that appeared in LifeScience entitled “DNA Kits: Secrets of Your Past or Scientific Scam?” The article made some strong negative statements about genetic genealogy, and I took the opportunity to discuss the issues it raised.

Soon after, my concerns were echoed at Anthropology.net in “Anthropologist Meredith Small says DNA testing is a scam.” The author had many of the same concerns, and also attempted to explain the science behind the tests.

If you’re interested in learning more about the science, or furthering the discussion we’ve started, please feel free to leave a comment here or at Anthropology.net.

Dr. Moran at Sandwalk brought to my attention a recent segment about genetic genealogy on Marketplace called “Who’s Your Grand Daddy?” Marketplace is a Canadian television program. In his post, Dr. Moran states:

“I’m disturbed by the fact that we have a number of prominent bloggers pushing DNA testing. You’d think they would be all over this story. You’d think that they would be in the front lines in the attack on unscrupulous private companies who are overselling the idea of tracing your ancestors through your DNA. If you thought that you’d be wrong. Some of these bloggers are even denying there’s a problem.”

During the Marketplace segment, Johnna – a woman they interview who is interested in learning more about her ancestry – discovers that she belongs to Haplogroup H. Unfortunately, Johnna had expected to learn more about her ancestry, such as the names of ancestors. It would appear that Johnna did not do any research about genetic genealogy.

The journalist then wonders how the company (it happens to be Genebase) can make a claim that Johnna is related to Marie Antoinette. However, the results reveal that Johnna IS related to Marie Antoinette through her maternal line. They both belong to Haplogroup H, meaning that they both descended through their maternal line from a single woman. The problem at this point is that the DEGREE of relation is not clear – most importantly, it is not clear to many potential customers. This is the problem that has prompted so many journalists to pen articles or film segments.

The segment also attempts to drill home the fact that we are all from Africa. The statement is true, but there’s no reason to stop at that simplistic answer. There are many scientists who are working on this field of research, attempting to refine the analysis from “we are all from Africa” to “this DNA is strongly associated with this location.” Our DNA has changed in those last 150,000 years, and we can learn things from those changes.

I should also point out that regular readers know that I agree that more education is needed. The system is not perfect – I certainly don’t think genetic genealogy is a scam, but on the other hand there is always more room for the education of customers.

Genetic genealogy is not an invention of business. It was created by anthropologists, published in peer-reviewed articles, and borrowed by business. In the end, Johnna received the results of her test and an assignment into an mtDNA haplogroup based upon the scientific analysis. Unfortunately, Johnna incorrectly believed that she would be receiving much more.

The question comes down to this – who is responsible for the education of consumers? I am a person who thinks it is 50/50. The company should be as honest as possible and attempt to educate the consumer (and I agree that more can be done by these companies to increase awareness), and the consumer should do their best to learn more. Almost every genetic genealogy company has a website that contains a “learn more” section, and customer should read it before ordering. A quick check shows that Genebase has a “learn more” section as well, available here. Before you buy any expensive product, you should do some research first.

By the way, the strangest part of the video was when they googled “Genographic” and found ads for Genebase, as if that was a sign of bad business practice. Sort of bizarre.

I honestly don’t know what to do with this next article. Meredith F. Small Ph.D., an anthropologist at Cornell University, wrote a brief article at LiveScience entitled “DNA Kits: Secrets of Your Past or Scientific Scam?” Dr. Small’s article is largely a comment on the article that appeared earlier this fall in Science, “The Science and Business of Genetic Ancestry Testing” (I provided an analysis of the article here at TGG).

According to Dr. Small:

“[The quest for identity] also leads unwary seekers of the past right into the hands of scam artists who claim they can trace anyone’s DNA back to its source.”

The sentence is extremely misleading:

First – a scam artist is by definition a person who engages in a “fraudulent business scheme.” Although genetic genealogy can be controversial, I’ve never heard a single customer accuse a company of running a scam. To the best of my knowledge, these testing companies are using the best science available to test DNA and compare results to their databases. Are physicians running a scam if they use open-heart surgery to fix a heart, rather than a simple pill that will be invented in 5 years? All technology is based on the best developed science right now. A company might have a limited database or only test a limited number of markers, but this does not qualify them as running a “scam.”

Second – The sentence also implies that genetic genealogy companies promise too much, and that genetic genealogists are unable to decipher the limitations themselves. As my readers might remember I discussed this assumption here. Most genetic genealogists understand and embrace the limitations of genetic genealogy, and also work to help others understand that difference. More can be done, and many are working to make that happen.

Similar sentences include “claims that this analysis will tell you much about where you came from are downright fraudulent, anthropologist Deborah Bolnick of the University of Texas at Austin and 14 co-authors recently reported,” and “Instead of tracing our genetic past, what we get is a scientific scam”

I think one of the major problems of this article is that the author or the editor doesn’t seem to the understand the underlying science. There is a MAJOR difference between autosomal testing and mtDNA or Y-DNA testing. This includes the science behind the test, and the science behind the interpretation of results. For instance, the article includes the following sentence:

“But, [anthropologist Jonathan] Marks points out, these companies are preying on the public because they simply don”t have enough comparative information to pinpoint a gene on a world map.”

For all you genetic genealogy newbies out there, there isn’t a test on the market that attempts to “pinpoint a gene.” Dr. Small fails to establish any line between autosomal testing and mtDNA or Y-DNA testing:

Some autosomal testing does attempt to identify the approximate predominate location of certain DNA markers (SNPs), but genetic genealogy companies do not sequences genes (other than in the full mtDNA test). And contrary to the implication of the article, these companies attempt to give very broad locations, such as “Northern Europe”, or “Asia”, not a specific town or county. Autosomal analysis is based on peer-reviewed science, the best we currently have available. It is true that there will be MUCH better data in 5 years or 10 years, but that doesn’t mean that using today’s science is a “scam.”

As for Y-DNA or mtDNA tests, the results are most often used to place the tested individual’s haplotype into a specific haplogroup. The approximate origin of all haplogroups has been established by peer-reviewed science. There are a few companies that use that haplotype data to identify a potential source of the mtDNA, for example. Again, that identification is based on peer-reviewed science and proprietary databases. Additionally, most genetic genealogists are aware of the limitations.

Perpetuating the mistaken scientific understanding, along comes the most egregious statement in the entire article:

“More insidious, these companies pretend to trace your unique ancestry through mitochondrial DNA, but that’s simply not possible. A few hundred years, a few generations, and every person’s history is a genetic mishmash. One little gene isn’t going to inform anybody about anything.”

It is obvious that Dr. Small either does not understand the underlying science, or is completely glossing over it. For the newbies, mtDNA is passed on almost always completely unchanged from mother to child. Every once in a great great while, that mtDNA changes in a very small way (that is, it gains a mutation). It does not “mishmash” with other mtDNA.

The mtDNA I inherited from my mother was inherited through an unbroken line of women until it ended with me. Employing genetic genealogy, I can trace my “unique ancestry through mitochondrial DNA.” I belong to Haplogroup A, which means that my maternal line crossed the Bering Strait thousands of years ago and settled in Central America. This is not conjecture, and I was not “scammed.” I used peer-reviewed science to come to that conclusion.

Now I confess that the mtDNA test only told me about a TINY percentage of my genetic heritage, but it was an exponential growth of information compared to what I had previously, which was nothing. And note, of course, that assignment of mtDNA into a specific haplogroup is based on single nucleotide markers, NOT on the sequencing of a gene.

The same holds true for Y-DNA testing. Although the markers used for comparative analysis appear to mutate somewhat more rapidly than mtDNA, Y-DNA is still passed largely unchanged from father to son.

And I felt that the concluding paragraph was dismissive:

“If you want to know who you are, look in the mirror. Written on your face is countless generations that have survived to reproduce, and the only thing you can realistically do at this point is thank them and then move forward.”

Genetic genealogy is a valuable part of my life. Although it doesn’t define who I am, it is a part of my identity. Attempting to learn more about myself and my ancestors through my genetic makeup has been a valid and rewarding endeavor. And the current field of genetic genealogy is only at the tip of the iceberg – so far we’ve been looking at a few random SNPs in our genome. Wait until science gets ahold of my entire genome.

P.S. -I will be sure to email Dr. Small about this post, so that she can respond to my criticisms.

Andy Sullivan is a general-assignment reporter for Reuters and just wrote “DNA Tests Don’t Always Help Uncover Family.” The article discusses his recent experience with genetic genealogy, including a Y-DNA and mtDNA test from DNA Ancestry.

Although the article is a little light on the genetic genealogy and incorporates a discussion of an online genealogy database, it is always interesting to read an article by someone who has just been tested. As I was reading the article, the following paragraph jumped out of the page and slapped me in the face:

“These tests promise to reveal long-lost relatives, uncover roots obscured by slavery, or simply allow those curious about where they came from to skip all that tedious digging.”

Ouch. At its best, genetic genealogy can do the first of those two things, if the person has or is willing to do their homework (i.e. traditional genealogical research). Genetic genealogy will rarely allow an individual to skip the wonderful pasttime that is genealogy (or “tedious digging”, as Mr. Sullivan calls it). Am I the only one who loves the “tedious digging”?

Almost every proponent of genetic genealogy attempts to emphasize the fact that testing does NOT promise anything other than sequencing data, perhaps a haplogroup assignment, and some controversial ancestral percentages from autosomal testing. The rest comes from the hard work of research such as comparing results to known or potential relatives, entering the information into DNA databases, and good old-fashioned detective work.

On the other hand, the next paragraph is absolutely true, and one that is not stated enough:

“But as I found out, the results can be underwhelming.”

Tested individuals often find that the results are not as exciting as expected. Of course, that might be due to statements they read that are similar to the ‘promise paragraph’ above.

[This is a repost of an article that appeared on May 29, 2007. Since I’m knee-deep in final projects and exams, I thought I’d pull out a popular article from the archives. I hope you enjoy it (again)]:

In Part I, Part II, and Part III of the “You and the $1000 Genome” series we’ve examined the Archon X PRIZE for Genomics, the International HapMap Project, and the ethical issues associated with both. In this final installment of the series we will examine the potential impact of genomic or SNP sequencing and interpretation on both medicine and genealogy (finally, some genealogy for you patient genealogists out there!).

I believe that whole genome sequencing will have myriad uses. In the paper mentioned in Part III of the series (John A. Robertson, “The $1000 Genome: Ethical and Legal Issues in Whole Genome Sequencing of Individuals (pdf).” 2003 The American Journal of Bioethics 3(3):InFocus), Mr. Robertson suggests that demand for personal genome sequencing outside of the medical context could be quite limited. But that view might fail to take into account uses of genomic information other than identifying or predicting disease, such as the genetic genealogy setting. Very few could have predicted 10 years ago that thousands of genealogists would be submitting their DNA for limited sequencing as they are doing today. If information from whole genome sequencing can be used to analyze genealogy (which it surely will be), then this will create an entire niche that will increase commercial demand outside of the medical context. And this is only one such niche. There might be many many more, some of which will only develop after whole genome sequencing becomes economically available.

Here is a list of just a few of the uses of genomic sequencing:

1.Identification of genes involved in disease – scientists are far from understanding the genetic basis of most human conditions, both normal and disease. Having thousands of genomes in research databases will give researchers the ability to make these types of associations through comparative genomics.

2.Tailored preventative medicine – knowing one’s propensity for disease(s) will allow scientists and medical specialists to attempt to prevent the formation of these diseases. So see more about personalized genetics, read this informative interview at ScienceRoll with Steven Murphy, MD of the Gene Sherpa. If tailored preventative medicine is to come about, it will require the education of all healthcare specialists in genetics and the relationship between genetics and disease.

3.Genealogical research – whole genome sequencing will greatly advance the ability of genealogists to use DNA to study ancestral relationships. This will have a big effect on both autosomal and Y chromosome studies. Genealogical testing using autosomal markers is limited by both the low number of identified markers and the unknown frequency of sequences across all populations. Cheap and efficient genomic sequencing could alleviate both these limitations. Y chromosome studies will greatly benefit by a huge increase in the number of STR markers that could be used for relationship comparisons. Currently companies such as Family Tree DNA offer 67-marker tests. In a few years we will be able to compare all the STRs in the Y chromosome rather than just a few of them.

Recognizing the impact that cheap and efficient whole genome sequencing will have on science and society, Nature Genetics‘ ‘Question of the Year’ is “What would you do if this sequencing capacity were available immediately?” The website has numerous replies from prominent geneticists and presents a number of interesting thoughts on the topic. evolgen, another member of The DNA Network, has also provided an answer to the question on the evolgen blog. In addition, DNA Direct Talk has a round-up of recent blog discussions regarding the $1000 genome.

Here is a quote from Professor Stephen Hawking in support of the X PRIZE in Genomics:

“As you may know, I have recently expressed my belief that space exploration and the eventual colonization of space is critical for humanity’s survival. To bring about breakthroughs for personal spaceflight is a laudable aim and it is work done by the X PRIZE Foundation that will eventually unleash humanity from the gravitational bonds of earth. You may also know that I am suffering from what is known as Amyotrophic Lateral Sclerosis (ALS), or Lou Gehrig’s Disease, which is thought to have a genetic component to its origin. It is for this reason that I am a supporter of the $10M Archon X PRIZE for Genomics to drive rapid human genome sequencing. This prize and the resulting technology can help bring about an era of personalized medicine. It is my sincere hope that the Archon X PRIZE for Genomics can help drive breakthroughs in diseases like ALS at the same time that future X PRIZEs for space travel help humanity to become a galactic species.”

Well there you have it! It is probably quite obvious that I have high hopes for efficient and inexpensive genome sequencing and subsequent interpretation. Although the necessary technology is still a few years away, it is important that we as a society address the many issues that will result from these technologies. As always, I would appreciate any comments that you many have on this topic, or any thoughts you may have had while reading this series.

P.S. – I just stumbled across an interesting article at In the Pipeline about the use of cheap(er) genomic sequencing to follow the development of antibiotic resistance in bacteria (S. aureus). I don’t have access to the PNAS paper, but it appears that the genome (which is tiny compared to ours) was completely sequenced twice, once before treatment and once after treatment failed due to the development of resistance. The strain had developed a total of 35 mutations! The author makes a great statement at the end:

“The technology involved here is worth thinking about. Even now, this was a rather costly experiment as these things go, and it’s worth a paper in a good journal. But a few years ago, needless to say, it would have been a borderline-insane idea, and a few years before that it would have been flatly impossible. A few years from now it’ll be routine, and a few years after that it probably won’t be done at all, having been superseded by something more elegant that no one’s come up with yet. But for now, we’re entering the age where wildly sequence-intensive experiments, many of which no one even bothered to think about before, will start to run.”

Other Posts in the Series:
You and the $1000 Genome – Part I: The Archon X PRIZE for Genomics
You and the $1000 Genome – Part II: The International HapMap Project
You and the $1000 Genome – Part III: The Ethical Issues

[This is a repost of an article that appeared on May 26, 2007. Since I’m knee-deep in final projects and exams, I thought I’d pull out a popular article from the archives. I hope you enjoy it (again)]:

In Part I and Part II of the “You and the $1000 Genome” series we examined the history of the Archon X PRIZE for Genomics and the success of the International HapMap Project. Today we’ll talk about some of the ethical issues associated with efficient and inexpensive genome sequencing. The value of whole genome sequencing will only be realized if individuals believe they have complete and legal control over their genetic information. I am greatly indebted to a thorough analysis of this issue by John A. Robertson at the University of Texas School of Law (”The $1000 Genome: Ethical and Legal Issues in Whole Genome Sequencing of Individuals (pdf).” 2003 The American Journal of Bioethics 3(3):InFocus). Note that this analysis is not intended to constitute answers to any of the ethical questions – it is only meant to be part of the discourse.

The ethics surrounding the X PRIZE competition has led the Foundation to establish an Ethics Advisory Board to identify issues that may be involved in whole genome sequencing and the conduct of the X PRIZE competition. The goal of the Ethics Advisory Board is to not only “comply with existing ethical and legal standards, but to promote public dialogue about some of the more controversial ethical, legal, and social implications of emerging genomic technology and to actively participate in setting standards for the future use of these technologies in research and clinical care.”

Ownership of DNA and Sequencing:
It is probably obvious that a person has almost total control over their own DNA as long as it is attached to their body. However, all day long we are continuously shedding our DNA into our surroundings, leading to the more difficult question; who owns DNA once it has left the body? If I find DNA on the sidewalk (such as a cigarette, a coffee cup, a piece of hair), does it belong to me or does it belong to the ‘shedder’? This was one facet of a recent New York Times article addressing the extreme tactics that some genetic genealogists have employed to obtain DNA from (potential) family members (”Stalking Stranger’s DNA to Fill in the Family Tree” 2 April 2007, Amy Harmon). Since DNA contains information that can be used to specifically identify a person, should we have total and complete control over our DNA unless we knowingly waive that right?

Informed Consent:
It goes without saying that written informed consent is a vital component of genomic sequencing. Consent is necessary for sequencing, interpretation, and any eventual research. Unique to genomic sequencing and interpretation, however, is the potential for emotional and psychological distress. There are always risks involved with discovering the information contained within our own genomes. As a result, entities, especially commercial enterprises, will have to delicately balance protecting their clients from the emotional consequences of genomic sequencing with protecting themselves from liability. This will necessitate educating their clients of the potential risks of sequencing and interpretation while obtaining legally sufficient informed consent.

The X PRIZE Foundation has directed that the “Genome 100″, the 100 volunteers who will contribute DNA to the sequencing competition, must give fully informed consent. Members of the Genome 100 (who will theoretically remain anonymous) will also be asked if they would be willing to contribute their results to a database that will be accessible to others.

The HapMap Project is also concerned about informed consent and has even provided an example of the consent form that they used when obtaining samples for the Project. According to the Project, “[e]ach of the DNA donors gave individual consent to participate in the Project and signed a consent form that grants permission for the DNA samples to be used in future studies approved by relevant ethics committees.” Interestingly, the Project also used teams of geneticists and ethicists to work in the communities to discuss the issues and educate the public about the science of the HapMap Project. Although the process was different in each country, “it involved a combination of individual interviews, focus group discussions, community meetings, and public surveys… and …created a climate in which research could proceed in an atmosphere of greater openness and trust.” This might be a good model for companies engaging in whole genome sequencing and/or genome interpretation.

Risks and Genetic Counseling:
There are numerous risks involved in whole genome sequencing and interpretation, including the discovery of medical and/or behavioral disorders, both present and future. These risks should be addressed by both informed consent (to warn customers of potential dangers) and genetic counselors (to help customers deal with the results of sequencing). The UCSC Genome Bioinformatics Group, for instance, has strongly supported the efforts of the National Human Genome Research Institute to train individuals to provide professional genetic counseling.

Storage:
How should samples be used once the DNA has been sequenced? Should they be stored or should they be destroyed? This will undoubtedly be an issue requiring informed consent.

Perhaps more importantly, how should results be stored? It is vital that results be protected from unlawful detection or use under any circumstances. Online storage will require advanced theft protection measures. Results shared in hard copy, such as via DVD, should also be strongly protected to avoid theft (a whole new type of identity theft). According to the X PRIZE Foundation, “[a]ll data generated as part of the X PRIZE competition will be stored in secure databases. The X PRIZE Foundation encourages continued research into creative and secure database structures.”

Discrimination:
Almost everyone would argue that discrimination on the basis of genetic information is not an acceptable use of genomic sequencing. Although there is no federal prohibition of this type of discrimination, many states have their own laws that prevent genetic information discrimination. And it appears that the federal government will soon pass the Genetic Information Nondiscrimination Act (See “GINA, A Primer“) to create an extensive nationwide prohibition of discrimination on the basis of genetic information.

Sequencing the Genomes of Minors:
Minors often have little choice in their medical treatment because that duty is carried out by their parents or legal guardians. But should parents have the right to sequence their children’s genomes? How about the genomes of embryos that are not implanted? What if there is a medical necessity? Perhaps sequencing in those situations should be limited to only those regions that are involved in the medical situation at hand.

The “Geneticization” of Society:
In his article, Mr. Robertson coins the phrase “geneticization of society” to address the concern that our genetic information will come to represent our identities. In our society, a person is ideally represented by their goals and achievements, not by their genetic information. Unfortunately, just as people are judged by their physical appearance in today’s society, there is the danger that people will be judged by their genetic identity in tomorrow’s society. Are we limited by our genetic information, or are we more than our own genome? In my opinion, our identity is what we make it, not a sequence of A,T,C, and G’s.

While researching the ethics of the $1000 Genome, I came across a terrific quote at (Genetic Engineering & biotechnology News) by Chad Nusbaum, Ph.D., co-director of the genome sequencing and analysis program at the Broad Institute: “Science is moving way ahead of the ethics. We can’t stop the technological advancements but the gap keeps widening. It is our responsibility to understand the implications of our work and educate the public and elected officials so that a proper dialog can take place.”

Other Posts in the Series:
You and the $1000 Genome – Part I: The Archon X PRIZE for Genomics
You and the $1000 Genome – Part II: The International HapMap Project

[This is a repost of an article that appeared on May 24, 2007. Since I’m knee-deep in final projects and exams, I thought I’d pull out a popular article from the archives. I hope you enjoy it (again)]:

In Part I of the “You and the $1000 Genome” series we examined the Archon X PRIZE for Genomics, a $10 million purse for the group that can sequence 100 genomes in 10 days for no more than $10,000/genome with an error rate below 0.001%. With today’s technology this goal is still a few years away.

But do we need an entire genomic sequence to obtain all the relevant medical information that our DNA contains? After all, 99.9% of my DNA is exactly the same as everyone else’s! Why sequence that 99.9% over and over and over if the results are the same every time? Wouldn’t it be cheaper to just sequence and then decode the 0.1%?

Sequencing that 0.1% is the goal of the International HapMap Project. HapMap stands for “Haplotype Map”, and those of you who are genetic genealogists will instantly recognize the importance of the word haplotype. The goal of the HapMap Project, begun in 2002, is to identify SNP groups (haplotypes) from a total of 270 individuals representing the Yoruba people of Nigeria, the Han Chinese in Beijing, the Japanese, and U.S. residents with northern and western European ancestry. The HapMap is essentially a catalog of all the common genetic variants in human beings.

Phase I of the HapMap project, which is complete, identified 1 million SNPs in the human genome. SNPs are “single nucleotide polymorphisms”, a single variation in the genetic code. According to some scientists, 1 million SNPs is about 10% of the total SNPs in the human genome. Interestingly, the results of Phase I of the HapMap suggested that SNPs tend to cluster together at certain locations and may be passed onto the next generation in groups. For many regions of our DNA there are only a few different haplotypes in most humans, and researchers can identify these haplotypes using just a few single SNPs. As a result, a single person’s genotype (collection of haplotypes) can be created by sequencing as few as 300,000 to 600,000 SNPs. For a recent review of Phase I of the HapMap Project, read this 2005 article in PLoS Genetics.

Phase II of the HapMap Project identified close to 2.5 million SNPs using the same 270 samples. Although data acquisition for Phase II has been completed, analysis is still continuing.

As the HapMap data becomes available, researchers can use it to identify genes and SNPs that are involved in disease. If most people with colon cancer share a certain haplotype, researchers can use that information to identify the genes involved and doctors can use that information to predict who might be susceptible to colon cancer long before the disease develops. I’ve previously written about two studies using information from the HapMap to identify a locus associated with diabetes and prostate cancer.

So with the huge success of the HapMap Project, do we really need genome sequencing? Some would argue that haplotyping is not sufficient, especially when a genetic disease is found at very low frequencies in the population. According to Jonathan Rothberg, the founder and chairman of 454 Life Sciences, “genotyping rests on the hypothesis that common alleles contribute to common diseases. What if very uncommon alleles contribute to common diseases? Only deep sequencing would be able to answer this question. The deeper the sequencing, the less frequent variant you can find. You need deep coverage to ensure the statistical likelihood of finding rare mutations.” Indeed, some mutations are so rare that they are only found within specific families or populations. If these families aren’t part of the HapMap Project, there is the potential that their personal SNPs won’t be identified.

Despite the concerns, there is little doubt that the HapMap Project is a valuable contribution to the field of personalized medicine. It has already produced results that will further our understanding of the genetic component of diseases such as diabetes and prostate cancer. While HapMap sequencing has limitations that differentiate it from whole-genome sequencing, it is a much cheaper and immensely useful tool for scientists and medical specialists.

[This is a repost of an article that appeared on May 22, 2007. Since I'm knee-deep in final projects and exams, I thought I'd pull out a popular article from the archives. I hope you enjoy it (again)]:

Over the next week and a half I will be examining the Archon X PRIZE for Genomics, a challenge from the Archon X PRIZE Foundation to foster the development of efficient and inexpensive genomic sequencing. Not only will the X PRIZE for Genomics change the face of medicine, but it will also have an ENORMOUS impact on the field of genetic genealogy, which we’ll discuss in Part IV of the series. Stay tuned for all the information you need to know about the prize, and if you have any thoughts or questions please leave a comment!

History of the Archon X PRIZE for Genomics:
In 2003 the J. Craig Venter Science Foundation announced a $500,000 Genomic Technology Prize that would be awarded to an the group whose technology significantly enhanced “the field of high throughput DNA sequencing by enabling a human genome to be sequenced for $1,000 or less.” The Foundation believed that crossing this threshold would enable the majority of individuals to afford genomic sequencing as part of medical treatment.

By 2006, Dr. Ventor’s $1000 genome challenge was picked up by the X PRIZE Foundation to create the Archon X PRIZE for Genomics, a $10 million dollar incentive for the first successful team. To win the prize purse, the registered group must build a device and use it to sequence 100 human genomes within 10 days or less, with an accuracy of no more than one error in every 100,000 bases sequenced (that’s just 0.001%) for no more than $10,000 per genome. As of May 2007 there are three teams registered for the competition; VisiGen, 454 Life Sciences, The Foundation for Applied Molecular Evolution (FfAME), and Reveo, Inc. If you’re curious, Genomics & Proteomics Magazine has summarized a number of the leading technologies that are being developed in pursuit of the X PRIZE (very technical information).

In August 2005, the National Human Genome Research Institute announced that it had awarded grants in excess of $32 million to promote the development of sequencing technologies that would significantly lower the cost of whole-genome sequencing. At the time, it cost roughly $10 million to sequence a human genome (a 50-fold decrease from the previous decade), and the NHGRI set a final goal of $1000 or less for an entire genome. As the NHGRI pointed out, “the ability to sequence an individual genome cost-effectively could enable health care professionals to tailor diagnosis, treatment, and prevention to each person’s unique genetic profile.”

Four years later, has there been progress?
454 Life Sciences, for example, has just announced in March that they have essentially completed sequencing of James Watson’s genome, arguably the first time a single person’s genome has been sequenced (the Human Genome Project’s source of DNA was reportedly an amalgam of different sources). For those that don’t know (can there be anyone?), James Watson is famous for having discovered the structure of DNA over 50 years ago. Interestingly, Watson has asked 454 to withhold his results for the apoE gene – associated with Alzheimer’s disease – as well as a number of other results, citing privacy concerns. Watson, after all, has a son who received 50% of his genetic makeup from Watson’s genome. In light of this, 454 has decided to hand over the results to Watson, who will then decided what to release to the public. (See Marshall, Eliot, “Sequencers of a Famous Genome Confront Privacy Issues” Science 30 March 2007:Vol. 315. no. 5820, p. 1780DOI: 10.1126/science.315.5820.1780). 454 estimates that the six-fold coverage of Watson’s genome cost an estimated $1 million. Still a long way to go to reach the $1000 goal.

Meanwhile, Reveo, Inc. just joined the competition on April 30^th of this year, but Reveo’s founder, Dr. Sadeg M. Faris, believes that their technology will eventually be able to read an entire human genome “in minutes for pennies per genome.”

In the next post I will be examining whether or not the $1000 genome is really necessary considering recent developments in a related field.

The X PRIZE Foundation has released a video that explains the aims of the project.

[Since this article posted on May 22, 2007, there have been MANY developments towards the $1,000 genome. To learn more, visit the archives here at TGG, or search using the search box in the sidebar.]

On November 27^th, the personal genome sequencing company Knome (pronounced like “Gnome”, the mythical creature) officially launched. From the company’s press release:

“‘Whole-genome sequencing is the endgame,’” according to Mr. Conde [Knome’s CEO]. ‘It will enable us to look at nearly 100% of your genetic code compared to the less than 0.02% currently available on SNP chips. This is the approach that most fully reveals what our genomes can tell us about ourselves.’”

“Pricing for Knome’s service will start at $350,000, including whole-genome sequencing and a comprehensive analysis from a team of leading geneticists, clinicians and bioinformaticians. This team will also provide continued support and counseling.”

Here’s a round-up of some recent conversation about Knome around the blogosphere:

Eye on DNA announced the launch, and then followed-up with “Eye on DNA Exclusive Interview with Knome CEO Jorge Conde”, a must read for anyone curious about the company!

The launch was also covered by DNA and You, SEQanswers, and GenomeWeb.

And, as usual, David Hamilton at VentureBeat: life sciences provides a great deal of interesting information about Knome. The launch was covered here, and an in-depth look at the company is provided in part two.

Misha Angrist at genomeboy.com compares the service of Knome with the Personal Genome Project.

The Gene Sherpa wonders if Knome is going to have some trademark issues.

Berci at ScienceRoll continues his fantastic series reviewing the websites and services of the launched personal genome analysis companies with a post about Knome.

I received an email from Denis Savard of the E3b Project, asking me to post the following for my readers. For the non-genetic genealogists, E3b is a Y-DNA Haplogroup (info here). The E3b Project was also ISOGG’s “DNA Project Website-of-the-Week” 14 Nov 2007.

Here’s the announcement:

Dear Readers,

The worldwide E3b Project proudly announces a new milestone: reaching the 700 member mark.

Since its launch this past June, the E3b project’s website (http://www.haplozone.net/e3b/project) has been steadily growing and is gradually being transformed into a dynamic place of learning, collaboration and research for all things related to E3b.

Here are some of the new developments from the last couple of months:

+ The new V-Series SNP tests have proven very popular among our E-M78 subclade participants and we have been very successful in further dissecting the E3b1a subclade into several distinct and finer branches. So far, about 70% of M78+ participants have also tested V13

+ (E3b1a2), which is the most prevalent European E3b subclade, and among these a single downstream M224+ (E3b1a2b) was also found. Of the remaining members that have requested the V Series test, 17.7% came back as V22+ (E3b1a3), and 11.4% came back as V12+ (E3b1a1). These and other statistics are periodically updated at the following page: http://www.haplozone.net/e3b/project/page/5

+ This last week the fall edition of the Journal of Genetic Genealogy has published the much anticipated research paper by E3b project’s collaborator Steven Bird, “Y-Haplogroup E3b-V13 as a Possible Indicator of Settlement in Roman Britain by Soldiers of Balkan Origin”. You can find and read this interesting document at this link: http://www.jogg.info/32/bird.pdf

+ Our database has recently been updated to include Elise Friedman’s extended haplotype cluster analysis, an in-house system which enables us to classify E3b haplotypes into well defined clusters based on allele similarities, which normally tend to correlate with biogeographical backgrounds. This focused analysis on individual haplotypes nicely complements the software based output from commonly used software applications that we use to create cladograms and neighbor joining diagrams, etc. Please go to the following page: http://www.haplozone.net/e3b/project/cluster

+ Another important trend in the last few months has been the inclusion of more collaborators who have volunteered to promote the project, to provide guidance to new members and take part in a collaborative effort to spread the new scientific discoveries and findings related to the origin, diffusion and phylogeny of this ancestral haplogroup.

+ Next comes our forum, the Double~Helix community (http://community.haplozone.net/), which has also proven itself as an ideal place for new E3b participants to inquire about their results or exchange their observations. Besides reading the opinions of regular participants, the team at hand will try to point out possible relationships of distinct haplotypes, predict a downstream mutation and identify a specific sub-cluster if enough markers are provided or maybe recommend specific additional testing.

If that wasn’t enough, Dr. Dirk Schweitzer is now preparing a basic guide to E3b, including subclade descriptions, geographic distributions, etc., since most online E3b reference pages currently available elsewhere are already outdated. A public link to this information will be announced here when available.

In sum, there are many exciting new things happening as we speak.

All that has been previously mentioned plus the inclusion of new haplotype data from relevant genetics population studies that enable members to match their haplotypes against a growing dataset is providing all members with new insight about their distant origins and helping us all to understand the bigger DNA picture.

Finally, we wish to thank all the Geographic and Surname Project administrators that responded to our recent request to invite their E3b participants to our haplogroup project. The response has been phenomenal and we’re sure your Project members will thank you for it. Here’s our FTDNA link: http://www.familytreedna.com/public/e3b

Best Wishes To All From The Team At The E3b Project.