The Genetic Genealogist

Welcome to the September 14, 2008 edition of Gene Genie!  Bloggers have begun to pick up posting with the end of summer, and it seems like everyday there’s a bunch of new interesting posts about the human genome.

96well at Reportergene presents “Trends in development of reporter genes.”  Reportergene is also looking for bloggers/reporters to join the blog’s community and help create the “main repository of news and tools for reportergenomists.”  See here for more information.

fightingfatigue presents » Have Japanese Researchers Found Diagnostic Tool for ME/CFS? posted at Fighting Fatigue.  According to a study discussed in the article, there might now be a test able to diagnose Chronic Fatigue Syndrome.

Genomes by the Handful

Human genomes are being sequenced by the handful these days.  Knome has recently delivered their first sequenced genomes to customers on 8gb USB drives placed in engraved boxes.  Additionally, news came last week that the first Arab genome had been sequenced.  As Mailund on the Internet asks, is this news anymore?

What good are all these genomes if the non-scientist citizen doesn’t understand anything about genetics?  Andrew at Think Gene discusses a lesson created by Dana Waring and colleagues at the Personal Genetics Education Project in “Personal Genetics Education Project: Lesson 1”

Lower Prices

On September 8th, 23andMe announced a reduction in the price of their DNA analysis from $999 to $399.  The news was discussed on Dienekes’ Anthropology Blog, Eye on DNA, bbgm, ScienceRoll, and at Geneforum.  It even led Attila to buy a kit.  The price drop also prompted a great discussion among some of the members of the DNA Network.  First, see “Cheap personal genomics: the death-knell for the industry?” at Genetic Future.  Andrew at Think Gene writes “23andMe Is DTC Genomics and Nobody Should Be Surprised” and “Why the “Database Sale Story” is Silly.”  This in turn is mentioned by Steve the Gene Sherpa at “A lot to chew and then spit!“  See also my “Follow-Up to 23andMe’s Price Drop.”

The Marriage Gene?

Mary Meets Dolly discusses “The marriage gene“, in which an article in the Baltimore Sun writes that “men who lack a particular variant of a gene that influences brain activity are more likely to be devoted, loving husbands and more likely to be involved with women who praise them as emotionally close and available.”  Rebecca Taylor mentions that genes are rarely the sole influencing factor in anyone’s behavior.

As a bit of housekeeping, if you aren’t already subscribed to the DNA Network, be sure to note that Daniel’s Genetic Future has moved to Scienceblogs.  Update your RSS feed!

Dinosaur Beer

Last but not least, news about ancient yeast.  Although this isn’t related to human genetics, I did my graduate research on yeast and thought I would indulge a little here.  Aminopop mentions that a new brewing company, Fossil Fuels, is making beer with revived 25-million year-old yeast.  Apparently, “the ancient yeast provides the wheat beer with a distinctively ‘clove-y’ taste and a ‘weird spiciness at the finish.’”

So ends the 37th edition of Gene Genie.  Edition 38 will be hosted in a few weeks.  You can submit your blog article for the next edition at the carnival submission form. Past posts and future hosts can be found on the blog carnival index page, or at the official Gene Genie blog!

Yesterday I wrote about 23andMe’s decision to lower their price to $399 (down from $999) while adding more genealogically-relevant SNPs and partnering with Ancestry.com.  Although I don’t have any further information about the new SNPs, I’ve seen a couple of interesting articles about the price drop around the blogosphere.

Aaron Rowe at Wired science writes “Human Genetics is Now a Viable Hobby.”  He notes that the new price is “well within the reach of cash-strapped grad students, frugal genealogy buffs and other not-so-early adopters.”  The comment thread is an interesting read as well.

“Cheap as chips”

Daniel MacArthur of Genetic Future writes “Cheap as chips: 23andMe slashes the price of personal genomics” at his new scienceblogs location.  Daniel also notes that the updated product “will certainly be popular with genetic genealogists” because of the addition of Y-DNA and mtDNA SNPs, and agrees with my hypothesis that other companies will follow suit and lower their prices.  Daniel also mentions the Personalized Medicine Collaborative (PMC) at the Coriell Institute for Medical Research, which is offering free personal genome scans to 10,000 individuals this year.

The Death of DTC Genetics?

Andrew Yates at Think Gene has suggested that free testing by the PMC will kill Direct-to-Consumer (DTC) genetics.  However, as Ann Turner commented on his post, the PMC does not return raw data, only interpretation of items they consider “medically actionable.”  This is the exact reason why PMC will not kill all DTC testing.  I think Andrew fails to appreciate that this is not a new world of genetic testing; genetic genealogists have been doing this for over 8 years now, and all we care about is the raw data.  The more raw data, the better.  Thus, history suggest that at least to the early adopters, raw data is vital.  Andrew answers Ann’s concerns by saying:

“So? I don’t get back the raw data of any other medical tests I take. If you just want a SNP sample of your genome because it’s cool, go buy a 23andMe or deCODEme test. That’s like getting an x-ray because you “want to see what your bones look like.” OK, some people may want to do this… and hey, I bought a 23andMe test for this reason… but most people aren’t choosing their x-ray test provider based on whether they get to keep their x-rays. “

But genetic genealogists (and undoubtedly many others) DO chose their testing provider based on the results they receive.  Sure, we like to know which haplogroup we fit into, but ultimately the most useful aspect of genetic genealogy is the comparison of Y-STR numbers (i.e. the raw data).  And genetic genealogy is an enormous market that has yet to be completely tapped.

(The other problem with Andrew’s assertion is that interpretation of genetic information (unlike a broken bone in an x-ray) varies; a SNP might mean one thing to company A based on study X, while it means another to company B based on study Y.  And this is, of course, an unavoidable result of the current stage of genomic science.  But why should I rely on just one source to interpret my genetic data?  Why can’t I interpret it myself or allow another entity to interpret it?  This is why entities such as SNPedia have recently been created.  After all, to use an analogy, aren’t you supposed to get a second opinion from a different doctor?)

And last but certainly not least, David P. Hamilton at bnet writes “23andMe’s Price Cut: The End of Commerical Personal Genomics?“  David suggests that 23andMe’s price cut is “an attempt to jump-start the data collection in order to kick the real money engine [data mining a large database of genotype/phenotype information created by 23andMe] into gear.”  However, he notes that this is a problem because it is difficult to extract phenotypic information from users, and because scientists can now afford to do their own large-scale genomic studies as the result of lowering prices (and free tests via the PMC).

See the new article at Seed Magazine “Inheriting Confucius,” which discusses efforts to generate a family tree containing the 2 million+ descendants of Confucius.

Kong De-Yong, a 77th(!) generation descendant of Confucius, has been compiling the tree for the last 10 years.  Although the Committee is accepting submissions from women and other previously excluded groups, it is not accepting DNA contributions.  According to the article, this “hints at the limits of Chinese engagement with the age of genomics, and demonstrates how high cultural stakes can constrain science.”  Unfortunately, as the author of the article suggests, many people might be afraid of the results of such DNA testing: “Given the potential implications of genetic knowledge for long-presumed members of the [Confucius] family, they think it better not to know.”

However, there is of course no need for the Committee’s participation in order to learn more about Confucius’ DNA or Confucuis’ descendants (although it would be nice, of course).  A Confucius DNA Project has already been initiated by the Beijing Institute of Genomics, and Confucius descendants can submit a sample for analysis for the price of $125.

Thomas Goetz has written another terrific article about genetic testing and the Personal Genome Project.  This article, entitled “The Gene Collector,” appears in Wired Magazine.  The article provides some new information about the PGP, including some of the incredibly detailed phenotype information that will be collected from the next 100,000 volunteers in the project.

The article also reveals the tenth and final participant of the “First 10″, the original 10 volunteers in the PGP.  I wrote about the first nine volunteers in the PGP almost exactly one year ago and noted that the tenth participant had not yet released his or her name.  The Wired article, however, mentions a number of participants including George Church, Esther Dyson, Rosalynn Gill, John Halamka, and Steven Pinker.  Indeed, a check of the PGP website confirms that Steven Pinker is the last PGP volunteer to be identified.

From the PGP-10 website:

“Steven Pinker, Ph.D. is the Johnstone Family Professor of Psychology at Harvard University, and has also taught at Stanford and MIT. His research on visual cognition and the psychology of language has won prizes from the National Academy of Sciences, the Royal Institution of Great Britain, and the American Psychological Association. He has also received five honorary doctorates, several teaching awards, and numerous prizes for his books The Language Instinct, How the Mind Works, and The Blank Slate. He serves on the Usage Panel of the American Heritage Dictionary and many editorial boards, and often writes for Time, The New York Times, The New Republic, and other publications. He has been named Humanist of the Year, and is listed in Foreign Policy and Prospect magazine’s “The World’s Top 100 Public Intellectuals” and in Time magazine’s “The 100 Most Influential People in the World Today.” His latest book is The Stuff of Thought: Language as a Window into Human Nature, published by Penguin books in the fall of 2007.”

There is more information at Dr. Pinker’s Harvard website and at Wikipedia.

Last week the genetic genealogy community lost one of its treasured members, Leo W. Little.

Leo’s passing was announced on the GENEALOGY-DNA mailing list on Sunday evening. Since then, many members of that mailing list, the ISOGG Yahoo Group, and the DNA- ANTHROGENEALOGY Yahoo Group have expressed their sympathy to Leo’s family and expressed their admiration for his work and contributions to the field of genetic genealogy.

Leo was the administrator of at least two DNA Projects, including the null439 DNA Project, and the Little DNA Project. The null439 group was begun by Leo after he helped characterize the “Little SNP” in 2002, a SNP that is also called “L1″ or “S26″. In 2005 Leo posted an email to the GENEALOGY-DNA that explained the discovery of the SNP, which defines the R1b1b2a1c Haplogroup in the new 2008 ISOGG Y-DNA Haplogroup Tree (previously known as R1b1c9a). The L1 SNP causes the primers used by Family Tree DNA to analyze Y-STR repeats at DYS439 to fail to anneal, and thus no result is recorded for that locus (i.e., it is “null”). The result is recorded as a default 12 with a blue asterisk. Here is Leo’s description from the null439 page:

“SNPs are passed down from father to son, and all males with a null439 SNP descend from a common ancestor who lived within the last 5000 years. Most null439 males with known origins have roots in England or Germany. The null439 SNP is also called “L1” or “S26“. L1/S26 is carried by about a half of one percent of R1b males. All males with L1/S26 also have the SNP “S21” (also known as “U106“) which defines the R1b1b2g subgroup (formerly R1b1c9).”

The null439 Project currently has at least 83 members, including myself. In June 2006 my Y-DNA analysis revealed that I have the L1 SNP and thus had no result at DYS439. When I joined the null439 project at FTDNA, Leo promptly emailed me and welcomed me to the group.

Other Contributions

But the S26 SNP and the null429 group are just a few of Leo’s contributions to the field. Other work includes his incredibly useful “Eclectic Genetic Genealogy Information” page, or a number of articles at the Little DNA Project (including this one entitled “Tracing the Borders Littles through DNA Testing“). Indeed, a search of the GENEALOGY-DNA archives reveals at least 150 messages posted by Leo’s email address (lwlittle@yahoo.com), and a search of his name reveals many more messages in which he was mentioned. Leo was a consultant for the Sorenson Molecular Genealogy Foundation, a member of the following organizations: the Association of Professional Genealogists, the International Society of Genetic Genealogy, and the Austin Genealogical Society. In July 2005, Leo’s work was highlighted in an article from Time magazine entitled “Can DNA Reveal Your Roots?“:

“One of the less controversial aspects of genetic genealogy is its ability to help people fill in gaps in their family tree. Leo Little, a retired engineer in Austin, Texas, had used historical records to trace his lineage back to his great-great-grandfather Thomas Little, who was born in Alabama in 1816. Then, he says, “I hit a brick wall. I knew my Littles were from the South, but there were a lot of Littles from the South, and it was impossible to sort out.” After he took a DNA test from Family Tree DNA, he began leading one of the company’s 1,900 surname projects, in this case checking test results on Littles. As a result, he has identified three distant cousins. By pooling their family records, the cousins have been able to trace their roots all the way back to 1680.”

Since Leo’s passing was so unexpected, the family is still dealing with the shock. On Monday, Terry Barton posted to the ISOGG Yahoo Group that the family had been contacted, and that Mrs. Little had requested that there be “no phone calls, no emails, no cards, no contact of any kind.” She did mention the possibility of a memorial fund in the future. Additionally, Mrs. Little indicated that she would try to respond to Leo’s emails at some point.

If you would like to leave a comment below, I will compile them and send them in letter to Mrs. Little when she is ready to receive mail. In addition, this post will be available indefinitely as a memorial to Leo Little. Thank you to Katherine Hope Borges for her assistance in completing this post.

UPDATE From Katherine (May 27 2008):

Leo was heavily involved in his church history project and donations may be made in his name to (with thanks to Derrell and Terry for sharing this info):

Highland Park Baptist Church
5206 Balcones Drive
Austin TX 78731

In DNA Fund, we will have fund designated for a “Leo Little Memorial Scholarship”, but since the 501(c)(3) is not yet in effect, contributions are not tax-deductible. However, contributions may be sent to DNA Fund’s General Fund at Family Tree DNA and will be designated for null research.

Although the genome scanning services offered by companies such as 23andMe, deCODEme, and SeqWright have been front and center in the press the last few weeks, I’m sure that the following information will not be included in any of the reports.

Comparisons

Two different sources have concluded that the scanning service offered by 23andMe and deCODEme, who use different types of Illumina SNP Chips, are highly reproducible. In January 2008, Ann Turner compared the results of testing at deCODEme and 23andMe, and concluded that of the 560,163 SNPs that overlapped and had a “call” (meaning there was a measurable result), they agreed on 560,128 and disagreed on 35. Ann wrote in January:

In all of [the disagreed calls], one company would make a homozygous call while the other company made a heterozygous call – there were no cases where they made a completely discordant call. All in all, I’d say that is pretty impressive.

The second analysis comes from Antonio C B Oliveira at Longa Vista, a new blog that appears to have been created to present these results and related information. Oliveira obtained results from 23andMe and deCODEme and compared the results, which are available here. He concluded that of the 560,299 SNPs that overlapped and had a call, the two scans agreed on 560,276 and disagreed on 23. The 23 disagreed upon SNPs are listed by chromosome. Oliveira writes:

This error rate seems to me to be quite acceptable and I wonder if this is the rate expected in scientific studies using the same technology.

Program to Compare Your Results

Interestingly, Oliveira created a computer program to analyze the results for him, and he has graciously made that program available “as a Windows executable and the source code is provided under the GNU General Public License.”

Conclusions/Thoughts

Note that Oliveira’s results contained 136 more overlapping results, presumably because of fewer no-calls in the data. Is Illumina able to produce more calls as they gain experience with the process, or is this an expected amount of variation from person to person? I would be interested to see more results and comparisons to determine the answer to this question.

HT: Genetic Future. If you’re interested in genome sequencing or personalized genomics, you should be reading Genetic Future. I highly recommend adding the feed to your reader. Genetic Future gave a hat tip about this information to Kevin Kelly at The Quantified Self. There, Kelly points out that none of the SNPs in Oliviera’s analysis are currently associated with any physical phenotype or disease. I hope Kelly plans to do a comparative analysis of his results, as that would be an interesting addition to the information provided by Turner and Oliviera.

A long-anticipated new version of the Y-Chromosome Tree will be released in the journal Genome Research tomorrow (Wednesday, April 2nd). In the paper, scientists from the University of Arizona and Stanford University use recent SNP data and research to reformulate the familiar Y-chromosome tree (see, for example, the current tree at ISOGG). Here is the full text of the press release.  The paper should appear here as soon as it is made available by Genome Research tomorrow.

From the press release:

In an article published online today in Genome Research (www.genome.org), scientists have utilized recently described genetic variations on the part of the Y chromosome that does not undergo recombination to significantly update and refine the Y chromosome haplogroup tree. The print version of this work will appear in the May issue of Genome Research, accompanied by a special poster of the new tree.

Hammer’s group integrated more than 300 new markers into the tree, which allowed the resolution of many features that were not yet discernable, as well as the revision of previous arrangements.

Furthermore, Hammer explains that this work has resulted in the addition of two new major haplogroups, S and T, with novel insights into the ancestry of both. “Haplogroup T, the clade that Thomas Jefferson’s Y chromosome belongs to, has a Middle Eastern affinity, while haplogroup S is found in Indonesia and Oceania.”

Here is the full citation of tomorrow’s paper:

Karafet, T.M., Mendez, F.L., Meilerman, M.B., Underhill, P.A., Zegura, S.L., and Hammer, M.F. New binary polymorphisms reshape and increase resolution of the human Y-chromosomal haplogroup tree. Genome Res. doi:10.1101/gr.7172008.

Here are a few of the many interesting links from the DNA blogosphere:

• DNA Testing Firms Eye Consumers (BBC) – yet another article that looks at both sides of the “should you test” debate.
• Genetic Testing Gets Personal (Washington Post) – a lengthy discussion of many different types of DNA testing.
• The Scientific Studies/Papers Page at ISOGG – I’ve been meaning to share this one for a while. The page describes methods for obtaining and reading scientific papers about genetic genealogy (or any other scientific topic, for that matter). This is a helpful resource for anyone who is interested in learning more about the science behind genetic genealogy.

If you’re interested in DNA, Native American History, or genetic genealogy, then you’re undoubtedly heard of a new paper from PLoS ONE called “The Phylogeny of the Four Pan-American mtDNA Haplogroups: Implications for Evolutionary and Disease Studies.” The authors, from all around the world (including Ugo A. Perego from SMGF and Antonio Torroni from Italy) analyze over 100 complete Native America mtDNA genomes. From the abstract:

“In this study, a comprehensive overview of all available complete mitochondrial DNA (mtDNA) genomes of the four pan-American haplogroups A2, B2, C1, and D1 is provided by revising the information scattered throughout GenBank and the literature, and adding 14 novel mtDNA sequences. The phylogenies of haplogroups A2, B2, C1, and D1 reveal a large number of sub-haplogroups but suggest that the ancestral Beringian population(s) contributed only six (successful) founder haplotypes to these haplogroups.”

All Native American mtDNA can be traced back to five Haplogroups called A, B, C, D, and X. More specifically, Native American mtDNA belongs to sub-haplogroups that are unique to the Americas and not found in Asia or Europe: A2, B2, C1, D1, and X2a (with minor groups C4c, D2, D3, and D4h3). Based on the study, the A2, B2, C1, and D1 groups are estimated to have developed between 18,000 and 21,000 years ago. Since the Native American mtDNA sub-haplogroups are not found in Asia, they are believed to have developed while founding groups were crossing into the Americas from Asia via Beringia.

The study suggests that 95% of Native American mtDNAs are descended from the six founding mothers of the A2, B2, C1b, Cc, C1d, and D1 sub-haplogroups. The other 5% is composed of the X2a, D2, D3, C4, and D4h3 sub-haplogroups.

It should be noted that these results are not considered the last word on the subject, as more sequences and further research is needed. From the paper:

“Our snapshot of the phylogenies for haplogroups A2, B2, C1, and D1 is only partially representative of Native American mtDNA variation, since most likely it only marginally includes the variation of Native American populations from Central and South America.”

For more information:

• Genes link 95 percent of American Indians
• Study: Native Americans Can Trace DNA to 6 Women
• Indian “Founding Mothers” Unveiled
• Native Americans Traced to 6 ‘Founding Mothers’
• Indian DNA Links to 6 ‘Founding Mothers’
• Sorenson Molecular Genealogy Foundation and University of Pavia Publish Most Comprehensive Answers to Date on Genetic Origins of Native Americans

On the heels of my recent post discussing all the interesting information that’s recently entered the blogosphere about genetic genealogy and DNA studies, here are a few more:

Misha Angrist, one of the Personal Genome Project’s “First 10“, wrote an article about the inevitability of DNA sequencing at News Observer. The article is a response to a recent editorial in the NEJM.

VisiGen Biotechnologies announces that IF their technology works as planned, the $1000 genome is just months or a few years away. See more at Genetics and Health and Next Generation Sequencing. Pacific Biosciences (PacBio) has made a similar announcement.

John Hawk’s Anthropology Weblog, “Viking Ancestry, Surnames and Medieval Genetics” examines a recent study in Molecular Biology and Evolution “investigating whether the Viking influence on surnames in England is mirrored by Y chromosomes.” It’s a great post, especially for genetic genealogists.

At Anthrpology.net, “Genetic Structure of Native American inferred from diversity in 280 bases of mtDNA.” The original paper is here. The abstracts states that “In this study, we analyze the mitochondrial DNA sequence between positions 16040 and 16322 of the Cambridge reference sequence. Our sample represents a total of 886 people from 27 indigenous populations from South (22), Central (3), and North America (2).” The authors find that “Eastern South America harbors more genetic variation than has been recognized.”

Examination of Chinese mtDNA and Y chromosomes in “Pinghua population as an exception of Han Chinese’s coherent genetic structure”, co-authored by the Genographic Project, reveals that the Pinghua, a small subgroup of Han Chinese, have non-Han Chinese genetic origins. The results are discussed at Yann Klimentidis’ Weblog and Diekenes’ Anthropology Blog.

A new paper examines the ancient migration across the Bering land bridge in “A Three-Stage Colonization Model for the Peopling of the Americas.” Particularly interesting to anyone with Native American Y-chromosomes or mtDNA (such as myself!). See more discussion at Anthropology.net.

Illumina has sequenced the first African genome from an anonymous Nigerian male sample in the HapMap project. The sequencing “yielded over 3.7 million single nucleotide polymorphisms (SNPs), including more than one million novel SNPs.” HT: Next Generation Sequencing.