11 Mart 2008 Salı

Who Crossed the Bering Land Bridge?

How many founding Asian groups braved their way across the Bering land bridge during those frigid Pleistocene ice ages? Was it a single wave of people who later developed into the three distinct linguistic and cultural groups that populated the Americas, or were there multiple waves of people each with their own language and culture? Or was it some mix of the two? The issue has been and continues to be a topic of debate.
Linguistic studies of the Na-dene, Aleut-Eskimo, and Amerind language groups suggested that there were three waves across the land bridge, one for each language group. Recent genetic research, however, has suggested that there was only a single wave of founding groups into the Americas. (Read a free online review here).
Let’s assume, for the moment, that there was only a single wave of migration into the Americas over the Bering land bridge. The next obvious question might be, who was in that group? Like the previous question, this one can also be addressed with recent advances in genetic research, particularly the use of mitochondrial DNA. The current dogma (which in your opinion may or may not be struck down by today’s article) is that there were 5 founding haplogroups – A, B, C, D, and X. Indeed, the vast majority of Native Americans tested in modern times as well as ALL previous ancient remains have belonged to one of those five haplogroups.
A new study from a group of American and Canadian anthropologists has revealed the existence of sixth founding haplogroup in prehistoric Native Americans. DNA was extracted from the remains of two individuals found together in central British Columbia dated at 4950 +/- 170 years old and the haplogroup was analyzed through sequencing. Both individuals belonged to haplogroup M with the mutations 16093, 16213, and 16223. This is the first time that haplogroup M has been detected in Native American samples, either modern or prehistoric. Importantly, haplogroup M is found in Siberia, the source of the Native American’s ancestors.
What impact does this have on Native American studies? Together this study and another, discussed recently here on this blog, suggest that more than five haplogroups settled the Americas, and within each haplogroup there may have been more than a single haplotype. This could significantly reduce many of the estimates for the timing of the peopling of the Americas.

Governmental Regulation of Genetic Genealogy Tests?

Senator Edward Kennedy (D-Massachusetts) proposed a piece of legislation before the United States Senate on 1 March 2007 called the “Laboratory Test Improvement Act.” The Act is proposed as a series of amendments to the Federal Food, Drug, and Cosmetic Act (FFDCA).
Sen. Kennedy’s statement(pdf) before the Senate, found in the Congressional Record from this month, defines his goal as “[ensuring] the quality of clinical tests used every day in hospitals and doctors’ offices across the country.” Additionally, he pointed out that the “tests are being used to diagnose illnesses, predict who is most susceptible to specific diseases, and identify persons who carry a genetic disease that they could pass on to their children.”
On his website Sen. Kennedy posted a news release that clarified his position:
“The legislation will mandate that all providers of “homebrew” laboratory tests provide the FDA with evidence that verifies their analytical and clinical validity. All of the information submitted to the FDA will be compiled into a database, which will subsequently be made available to the public on the Internet. Presently, an overwhelming majority of the laboratory tests employed by health care facilities are homebrew tests that have not been approved by the FDA. In some instances, homebrew tests are used to diagnose Huntington’s disease and susceptibility to breast cancer. As such, the results of homebrew tests affect the lives of thousands of Americans and their families each and every year.”
Sen. Smith (R-Oregon), co-sponsor of this Act and Ranking Member of the Senate Special Committee on Aging, chaired a hearing in 2006 entitled “At Home DNA Tests: Marketing Scam or Medical Breakthrough?” that addressed the lack of regulation of “homebrew” genetic testing products.
So will this legislation affect the thousands of genetic genealogy tests sold by DNA laboratories in the United States? Most likely not, since genetic genealogy tests do not appear to fall under the ‘intent’ of the Laboratory Test Improvement Act. Rather, it would seem to include companies such as the nutrigenomics company MyCellf (discussed in a previous post) which screens DNA for gene variants associated with disease. Currently, genetic genealogy tests do not intentionally diagnose obvious disease variants (could CCR5, offered by FTDNA, be considered part of this group?).
The Laboratory Test Improvement Act defines a “laboratory-developed test” as one that uses “analytical methods developed by a laboratory to process a biological specimen, whether at 1 laboratory site or multiple sites, to report a test result to a health care practitioner, a patient, or a consumer; and includes an in vitro diagnostic product that the laboratory has modified, unless such modification requires preclearance or preapproval of such modified in vitro diagnostic product under this Act.”
The Act specifically excludes:1) “the processing of a biological specimen to: a) determine paternity, b) aid in forensics, or c) conduct research if the result of the test is not reported to a health care provider, a patient, or a consumer;2) An in vitro diagnostic product; or3) An analyte specific reagent [defined in the Code of Federal Regulations].”
The Act also states that laboratory-developed tests shall be classified as a “device” under section 201(h) of the FFDCA. Section 201(h) defines device as “an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is [among other things] intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, in man…”
Based on the ‘intent’ of the legislation (suggested by Sen. Kennedy’s press release and statements before the Senate) and the definitions contained in the Act, it is unlikely that tests offered for genetic genealogy will fall under the scope of the Laboratory Test Improvement Act.
It is possible that companies offering genetic genealogy testing might be forced to comply with the Laboratory Test Improvement Act in the future if the scope of their sequencing grows. As whole-genome sequencing becomes cheaper and cheaper, companies will want to offer many more options to their customers, including disease gene variants. After all, unless the mutation is spontaneous we inherited the variant from our ancestors. Already the media is filled with stories of whole families that possess a dangerous allele and are submitting their DNA for testing. The line between testing for genealogical purposes and for purely genetic purposes is fading. That being said, the Laboratory Test Improvement Act clearly does not forbid any of the testing described. New “homebrew” tests will be allowed to come onto the market without FDA review provided they a warning that they have not been FDA-cleared or –approved. Perhaps this could benefit consumers by preventing testing by companies who offer sub-par services.
The Text of the proposed legislation is available here. Here is a blog discussion of the legislation and a news article that mentions Genelex, a company that offers both genetic genealogy tests and disease gene screening.
What are your opinions on this topic?

DNA Testing Jumps During Black History Month

With the arrival of Black History Month and following on the heels of PBS’s popular series ‘African American Lives’, increasing numbers of African Americans are deciding to explore the world of DNA testing and genetic genealogy. As a result many newspapers and magazines are taking the opportunity to introduce their readers to this increasingly popular avenue of genealogical research.
The Rocky Mountain News in Denver, Colorado is currently three articles into a six-part series examining the role and effect of genetic genealogy in African American research [Thanks to Genealogy Reviews Online]:
Saturday, 17 February 2007 (Two articles, here and here).Monday, 19 February 2007Tuesday, 20 February 2007Wednesday, 21 February 2007Thursday, 22 February 2007Friday, 23 February 2007
Fortune Magazine published an article, ‘Tracing African Roots Through DNA’, on February 16th in which the author uses the DNA testing firm African Ancestry to analyze his mtDNA and Y chromosome. The article also describes the (positive) psychological effects the results have on himself and his family.
Another magazine, Diverse: Issues in Higher Education has an older article, ‘Regaining a Lost Heritage‘. The author of this article also tests her mtDNA through African Ancestry. Interestingly, the author cites Dr. Bruce A. Jackson, Co-director of the African-American DNA Roots Project at the University of Massachusetts Lowell. Dr. Jackson explains his skepticism of African Ancestry’s ability to pinpoint a person’s mtDNA or Y chromosome ancestry to a single ethnic or geographic group because the databases are still so small. African Ancestry, however, contends that their DNA database is 5 times larger than any other comparable databases.

dna genes in fashion

Here are some recent news articles that mention the use of genetics in traditional genealogy:
Internet databases, DNA testing make genealogy an easy pursuit - but only for some – An Associated Press story about the use of DNA testing for people researching genealogy in countries (such as Asia, Africa, etc…) with few online databases.
Genes in fashion – The anthropology department of the California State University has tested the DNA of hundreds of students to create an exhibit called “Immigrants All! Our Migration Tales and Genetic Trails” in the department’s museum.
To Whom Else Does Your DNA Belong? – A response to reporter Amy Harmon’s recent story in the New York Times. Although I don’t agree with the strict opposition voiced in this student article, the title is very similar to the title I chose for my own response.
McCoy tempers in famed feud may have genetic cause – Many of the McCoy’s, one of America’s most famous feuding families, have a genetically inherited disease caused Von Hippel-Landau which cause tumors of the adrenal gland. This can lead to high blood pressure and hot tempers. It turns out that geneticists have been studying and publishing about the family for over 30 years and have traced the disease through at least 4 generations.
Rogue-gene discovery could end family’s tragedy – Another story about using genetics and genealogy to trace the distribution of a devastating mutant gene through a family. This gene, which triggers stomach cancer, has ravaged at least 5 generations of a family in New Zealand.

From the NYT: DNA Tests Offer Immigrants Hope or Despair

Although the article in today’s New York Times - “DNA Tests Offer Immigrants Hope or Despair” by Rachel L. Swarns - uses traditional paternity or maternity tests and not genetic genealogy tests, the emotional results of the tested can often be the same. What if DNA proves that your father isn’t your biological father? What happens when there is uncontestable proof that there was an NPE (non-paternal event) in your great-grandfather’s ancestry?
According to the article, federal officials in the Immigration Department are using “genetic testing to verify the biological bonds between new citizens and the overseas relatives they hope to bring here, particularly those from war-torn or developing countries where identity documents can be scarce or doctored.”
For example, Isaac has been in the U.S. away from his native Ghana and his four boys for 14 years. When he became an American citizen and the Immigration Department suggested that he take a DNA test to prove the biological relationship to his four sons, he agreed. Unfortunately, only the oldest boy was his biological child. That child could come to the U.S., but Isaac would have to find another way to bring over the other three children.
How often does this happen? “Mary K. Mount, a DNA testing expert for the A.A.B.B. - formerly known as the American Association of Blood Banks - estimates that about 75,000 of the 390,000 DNA cases that involved families in 2004 were immigration cases. Of those, she estimates, 15 percent to 20 percent do not produce a match.” That’s over 10,000 cases in one year alone!
Interestingly, many lawyers working with immigrants believe that the government’s use of DNA testing burdens immigrants because of the high price of the testing - as much as $450 to test a parent and child. As well, federal officials “acknowledge that genetic testing can carry an emotional toll.”
This is true for any type of testing, be it a paternity test, an mtDNA test, or (someday) a full genomic sequencing. Everyone has a picture of their own past in their mind, a collection of beliefs and identities that they’ve learned or heard or perhaps have made up. Evidence of another past based on DNA can often shatter those beliefs.
As these families struggle to come to terms with the results of the testing, they often come to the conclusion that the biological definition of family is not the only definition available. My favorite line in the story comes from Balfour Francis, a 44-year-old Jamaican-born welder in Brooklyn who is trying to have his daughter join him in America. After the DNA test showed that he is not the girl’s father, he stated, “I will not let anybody dictate who is my child.” Although the results can be painful and have a severe emotional toll, they do not change the love a parent has for a child.
As for Isaac, his immigration lawyer determined “that he could petition for the teenagers as their stepfather. He must prove that the boys are the children of his deceased wife. Isaac hopes that a DNA test of one of his wife’s siblings, which could be compared with that of the teenagers, would provide that proof.”
I highly recommend reading this article if you are interested in DNA testing. I’m sure that this will spark another wave of insightful and interesting discussion on the blogosphere, similar to the very controversial article I discussed previously here.

Faces of Britain

In 2005 the Wellcome Trust established a £2.3 million project (roughly 4.5 million USD) at the University Oxford to examine the genetic makeup of the United Kingdom. The project would be led by the renowned geneticist and Oxford Professor Sir Walter Bodmer, joined by Oxford Professor Peter Donnelly (a population genetics and statistics expert) and the Wellcome Trust Principal Research Fellow Professor Lon Cardon.
The goal of the project is to establish a knowledge base for analyzing genes that are linked to disease. To do this, the researchers hoped to gather DNA from 3000 to 3500 volunteers throughout the UK who live in the same area as their parents and grandparents. Each volunteer’s DNA will be tested for 2000 SNPs (single nucleotide polymorphisms). The data will be combined with each volunteer’s medical history in the attempt to find a link between genetic make-up and the inheritability or susceptibility of a number of diseases such as diabetes and Alzheimer’s. The data will also be used to isolate DNA sequences that characterize the founders of each region of the UK, be they Viking, Saxon, or Celt.
“Our aim is to characterise the genetic make-up of the British population and relate this to the historical and archaeological evidence,” says Professor Bodmer. “We are collecting samples from people in rural areas with all four grand parents from the same area so as to avoid the recent mixing up of populations in urban areas and to reach back in time as far as possible.
“Our samples will provide a valuable control for studies on disease susceptibility which depend on comparing the frequency of genetic markers in disease groups with that in control groups. If we are able to eliminate genetic markers linked to geography rather than disease, then we should be able to minimise the risk of finding spurious associations.”
To date, the researchers have collected approximately 1,500 samples and have analyzed the Y chromosomes of the male volunteers. The M17 variant of the Y chromosome, for example, is found in 20% of people from Norway but is very rare elsewhere in Western Europe. In the Orkney Island, almost 30% of the tested males have this variant, suggesting that the Norse Vikings settled the Islands. Surprisingly, the M17 variant is not found in areas where the Danish Vikings settled, supporting the conclusion that the Norse and Danish Vikings were genetically different.
Another interesting conclusion of the study so far is that two rare versions of the Mc1r gene occur at a much higher frequency in those areas that were settled by the Celts than in those areas settled by the Anglo-Saxons. These alleles of Mc1r are found in Scotland, Wales, Ireland, and regions of southwest England and are associated with red hair. In fact, Mc1r (melanocortin-1 receptor) is a member of the G-protein-coupled receptor family of proteins and it functions at the surface of specialized pigment producing cells called melanocytes. It is one of the key proteins in regulating hair and skin color.
Faces of Britain on Channel 4:
The researchers have also begun to present some of their findings to the public via the television series “Faces of Britain.” Last Saturday, April 14th, Channel 4 in Britain aired a program that highlighted the study’s current findings.
The findings, according to the program, supported the idea that the Viking invasion of Britain was predominately from Danish Vikings while the Orkney Islands were settled by Norse Vikings. Additionally, the results suggest that the Cornish people are a Celtic race that are more closely related to the Welsh than to their British neighbors (or should I say, neighbours).
The next Faces of Britain will be aired this Saturday, April 21st, but if you hurry you can watch the previous episode online for free (until Saturday) at www.channel4.com/od/.

Faces of Britain – The Book:
The study has also resulted in a book published in January of this year - “Face of Britain: How Our Genes Reveal the History of Britain” by Robin McKie. The book is available on the UK version of Amazon but I couldn’t find it here in the U.S.
Here is the publishers synopsis:
“Written into our facial features is a story going back generations. It is the story of who we are and where we are from - the history of Britain through war and conquest, migration and racial integration. The Channel 4 series, The Face of Britain, begins with the largest ever research project into the genetic make-up of the British public. The Welcome Trust has given a GBP2million grant to Oxford geneticist Sir Walter Bodmer to take DNA samples from hundreds of volunteers throughout Britain and find tell-tale fragments of DNA that reveal the biological traces of successive waves of colonisers - Celts, Saxons, Vikings, etc. - in various parts of Britain. These traces in part determine our facial features. In effect, this project will produce a genetic map of our islands revealing where today’s Cornish or East Anglians originally came from. The project is unique in that it uses cutting edge technology to question our accepted notions of our history. Added to this, the series and the book will meld science, history and personal stories to investigate our linguistic history, our surnames and placenames and compare findings with the results of the Bodmer study. The Face of Britain will be a launch pad to explore Britain’s earliest history while investigating why we look the way we do.”
Thanks to SpiritIndia.

Are aboriginal Australians and New Guineans the modern-day descendants of the extinct species Homo erectus?

Some scientists have hypothesized that Australian aboriginals received a portion of their DNA from an ancient hominid species called Homo erectus, which for a short time was contemporaneous with modern man. A recent study published in PNAS (Proceedings of the National Academy of the Sciences) set out to answer this question by analyzing mtDNA and Y-chromosome samples from aboriginals.
A total of 172 mtDNA and 522 Y-chromosome previously published and new sequences from aboriginal Australians and New Guineans were analyzed for mtDNA and Y-chromosome variation and were compared to the current world haplogroup tree. All of the mtDNA sequences were members of the M and N founder branches, and all of the Y-chromosome sequences fell into the C and F founder branches.
The results suggest that the Australian aboriginals are descendants of the same emigrant group that left Africa 50,000 to 70,000 years ago and populated Europe and Asia. At least from the small number of samples analyzed for this study, there does not seem to be any DNA contribution from Homo erectus.
The uniformity of the sequences suggests that once humans migrated into the region there was little other gene flow. This might explain why the Australian and New Guinean populations share phenotypic features that are unique to the region.
You can read more about this new study at National Geographic or NewScientist, or read the article online for free at PNAS. Additionally, Ron Scott at Scott Genealogy has provided a transcript (pdf) of an interview with Toomas Kivisild (one of the authors of the study and a name that many genetic genealogists will recognize).

Famous DNA Review, Part II – Genghis Khan

In 2003, researchers from around the world released a paper that suggested that 8% of all Mongolian males have a common Y chromosome because they are the descendants of Genghis Khan (See “The Genetic Legacy of the Mongols,” 2003, Zerjal, et. al., American Journal of Human Genetics, 72: 717-721). The researchers examined the Y chromosome variability of over 2000 people from different regions in Asia and discovered a grouping of closely related lines. The cluster is believed to have originated about 1,000 years ago in Mongolia and its distribution coincides with the boundaries of the Mongol Empire.
Genghis Khan’s empire (he ruled from 1206 – 1227) stretched across Asia from the Pacific Ocean to the Caspian Sea and was reportedly extremely prolific. Khan’s son Tushi had as many as 40 sons. His grandson Kublai Khan is reported to have had as many as 22 sons, and perhaps many more. Together this family may have as many as 16 million descendants alive in Asia today. It is extremely important to note that until DNA can be extracted from Khan’s bones (which have never been found), there is no definitive proof that this Y chromosome cluster is actually descended from Genghis Khan.
When Family Tree DNA compared the markers in the paper to their database they determined that the Y chromosome cluster belongs to Haplogroup C3 (M217+). Forty-seven samples in their database exactly matched the markers identified in the paper. The company has summarized the marker results from the paper and have made that information freely available.
A newly released study from Russian scientists examined the Y chromosomes of 1,437 men from 18 Asian ethnic groups (Altai Kazakhs, Altai-Khizhis, Teleuts, Khakasses, Shor, Tuvinians, Todjins, Tofalars, Soyotes, Buryats, Khamnigans, Evenks, Mongolians, Kalmyks, Tajiks, Kurds, Persians and Russians). The researchers discovered that approximately 35% of Mongolians possess the “Khan” Y chromosome. Surprisingly, the results of the study suggest that although the Mongol Empire held eastern Russia for 250 years, there are few “Khan” Y chromosome carriers in that region.
You can read more about the 2007 study at UK Channel 4 or at Scientific Blogging.

Lotsa Links - Forbes Magazine and Genetic Genealogy

The Forbes Series – Forbes has an excellent series of articles relating to genomic sequencing and genetic genealogy. It is well-timed and full of interesting things to think about. I highly recommend reading them all!
1. Will You Get Cancer?
2. The Telltale Tumor
3. Never Mind You – What About Me?
4. Genes of the Rich and Famous
5. Genealogy Gets Genetic
6. 12 Genes That Could Change Your Life

“Genome of DNA Pioneer is Deciphered” - This is a write-up by Nicholas Wade in the New York Times. Unfortunately, Mr, Wade used the word ‘deciphered’ in the article rather than ‘sequenced’. I’m not convinced that this was his choice, but he’s getting some flack for it. In any event, it appears that Watson’s sequence took 2 DVDs rather than just one! There’s a write-up at Nature News as well.
Additionally, the article states Dr. Craig Venter completed his own genome at the Venter Institute in Rockville, Md., and deposited in GenBank last week. There’s no way that the timing was coincidental; he obviously published his genome last week in order to beat Watson to the punch. According to a recent Nature News article (subscription only, here), an analysis of Venter’s genome will be described in a paper in the journal PLoS Biology, and he’s also writing a book, A Life Decoded: My Genome, My Life about his personal genome. The good news is that PLoS Biology is a free access journal, so the vast majority of the population who aren’t in academia can actually read and enjoy this article when it comes out! (In case you can’t tell, I’m a huge proponent of free and open publishing of data, especially that data funded with my tax dollars!!!).

Genetic Genealogy and the Amish

I am a genetic genealogist because I thought it would be a fun and interesting thing to do. Some people, however, are genetic genealogists because it is a matter of life and death.

The Amish/Mennonites and Genetic Disorders
The Amish migrated from Europe (Germany/Switzerland) to the United States in the 1700s. One such group, the Old Order Amish of Lancaster County, Pennsylvania, began with 200 Swiss immigrants. Today, there are roughly 200,000 Old Order Amish. Because of the difficult lifestyle, the lack of evangelism, and the language barrier, there is essentially no conversion to the Amish religion. In addition, marriage outside the community is forbidden. As a result, the community has remained closed for over 10 generations and is still using the same 200 genomes of their founders! This is known as “founder effect,” which means that a population is started by just a small number of individuals and as a result that new population will be different (both genetically and phenotypically) from the parent population, potentially with low genetic variation.
If I were to sequence the genomes of 200 individuals that I had somehow randomly selected, I would undoubtedly uncover a number of undesirable mutations hidden in their genes. Most of these mutations would not cause any detectable phenotype because these individuals would still have a healthy copy of the mutated gene (for the DNA newbies, we all carry 2 sets of 22 chromosomes plus 2 sex chromosomes, meaning that we have two copies of most genes).
Within the Amish populations, the mutated gene perpetuates and flourishes because it is never diluted into the general public. This means that it becomes increasingly likely that two individuals, both carrying a copy of the mutated gene, will marry and produce offspring. These children then have a random chance of inheriting two mutated copies of the gene.
Crigler-Najjar Syndrome
A recent article in USA Today, “Blue glow signifies life in peril in Pennsylvania Dutch country” analyzes the effect of one of the genetic diseases threatening the Amish. Crigler-Najjar syndrome is extremely rare, with only about 110 known cases in the entire world. Almost 20% of those cases are among the Amish and Mennonite in Pennsylvania.
People with Crigler-Najjar syndrome are unable to break down bilirubin, a natural waste product from old blood cells, and it builds to a toxic level in their blood. Untreated, the condition leads to brain damage and death. The afflicted, with yellowed eyes and golden skin as a result of their condition, are forced to spend 10 to 12 hours a day in bed underneath bright blue lights to… These beds cost about $1,000, and fans must be used to keep the children cool under the intensity of the lights. Although there is no cure, a liver transplant is one option.
The Clinic for Special Children
In 1990 a clinic opened in Straburg that specialized in children with rare diseases. The Clinic for Special Children was founded by Dr. Holmes Morton, who once worked with Dr. John Crigler, the physician who first described Crigler-Najjar syndrome in 1952 with Dr. Victor Najjar. The building, located on a site that was once an Amish field, was erected by 70 local men in the traditional barn-raising manner.
According to Wikipedia:
The clinic treats about 600 children for 80 different genetic disorders or syndromes such as glutaric aciduria (GA1), maple syrup urine disease (MSUD), Crigler-Najjar syndrome (CNS), and medium-chain acyl-CoA dehydrogenase deficiency (MCADD). Not all the children are Amish; about 15% of the caseload come elsewhere, including Africa and Asia. About 75% of the children are treatable—and a third of those are highly treatable, many through techniques developed at the center
There’s a great brochure available that provides an in-depth description of the Clinic. In 2006, Dr. Morton was awarded a MacArthur Foundation “genius grant” for his work. A well-deserved honor, if you ask me. Here is a list of some of the publications associated with the Clinic for Special Children. Here are some other articles about the Clinic, including the Genome News Network, the New York Times, Scienceline, Affymetrix, and here. For more information about the Amish/Mennonites and genetic disorders, see this brief review by Laura Weeks (pdf!).

Interestingly, there is a Swiss Anabaptist DNA Project at FTDNA, but unsurprisingly there are very few samples so far. Another interesting source of information about Amish/Mennonite genetic genealogy is the Yoder Family Website, which contains links to DNA testing by members of the Yoder Family.
Hsien at EyeonDNA wrote about this topic at Genetics and Health, and if you read the article, you’ll see that even her “doctorate genealogy” has a link back to Amish studies.