Genetic-screening companies face legal battle
Nature 453, 1148-1149 (2008)
The state of California is clamping down on companies that offer direct-to-consumer genetic testing in a move that threatens the burgeoning industry. Meredith Wadman looks at a grey area in US regulation.
Ed. Note: Genetic screening is a quasi-medical form of DNA testing, not at all the same as ancestry testing.
By Meredith Wadman
Last Wednesday, as California governor Arnold Schwarzenegger prepared to tell a biotechnology industry convention in San Diego that his state “is one of the best places to set up shop”, Kári Stefansson was opening a letter that had just landed on his desk at deCODE genetics in Reykjavik, Iceland.
The letter read: “It has come to the attention of the California Department of Public Health…that deCODEme Genetics is in violation of California law” for failing to have a clinical laboratory licence in the state and offering genetic tests to consumers resident in the state without a physician's order. It gave deCODE until 23 June to submit a plan showing how it would correct the situation, or face “civil and/or criminal sanctions”.
Stefansson's high-profile company is one of 13 genetic-testing firms that have been targeted during the past two weeks by the California agency with a letter to “cease and desist” selling tests to California's residents. The directive poses a serious challenge to plans for a new era of Internet-based, direct-to-consumer genetic testing. The companies include Californian businesses 23andMe and Navigenics, which have begun marketing test packages based on genome-wide arrays within the past six months, and DNATraits.com, based in Houston, Texas, which counsels prospective parents on the genetic risks faced by their future offspring.
DNA Direct, a San Francisco-based firm founded in 2003 that offers tests for familiar mutations in well-characterized genes such as BRCA1 and BRCA2 , which convey an increased risk of breast cancer, did not receive a letter.
“If these companies were constrained from reaching out to consumers directly, it would certainly cause some near-term difficulty for their business,” says life-sciences analyst John Sullivan at Leerink Swann, an investment bank based in Boston.
During a public meeting on 13 June, Karen Nickel, California's chief of laboratory field services, who wrote the letter, said that consumer complaints had triggered an investigation into 25 companies, of which 13 were ultimately sent letters. Nickel told the meeting: “We [are] no longer tolerating direct-to-consumer genetic testing in California.” Under California law, the companies could be fined up to US$3,000 per day for each violation if there is no “immediate jeopardy” to state residents — and from $3,050 to $10,000 per day if there is.
23andMe declined an interview request. It released a statement emphasizing that it is an “informational service”, and said it is “eager to work with” regulators in California and elsewhere to develop appropriate regulations to govern the nascent industry.
But two of the companies dispute the charges in the letter. Mari Baker, chief executive of Navigenics, based in Redwood Shores, says that its tests are read by a licensed, certified laboratory and that a company physician is involved both in the approval of a genetic-test order and when the results are released to a customer. “It's important to do this the right way,” says Baker. “And that we are doing. So this has come as quite a surprise. The only conclusion we can come to is we have not properly informed the state as to all the steps we have in place. We have reached out to them to try to schedule such a meeting.”
Stefansson says that deCODE is not marketing to California residents; its website lists California among several states for which the company's deCODEme Genetic Scan “may omit certain information” because of state law. He says that his company is in the process of trying to obtain a California licence, but that the state has been unresponsive. He is a physician and oversees the ordering process for deCODE, he says, adding that a large proportion of the test requests the company receives are from people's personal physicians.
“It doesn't increase your risk. It measures your risk.”
Even so, he calls the legality of California's requirement that a physician order a genetic test “questionable”. He says: “I don't think that they can basically tell the people of California that 'you cannot order a test like this for yourself without going to a physician'. I don't think they can raise that kind of barrier.” He argues that a genetic test is not a medical intervention like, say, a prescription for a cholesterol-lowering drug. “It doesn't increase your risk. It doesn't decrease your risk. It measures your risk. It's a description of who you are.”
The state Department of Public Health —which is no longer making Nickel available for interviews — declined to say whether a company-employed physician who oversees orders initiated by customers through the Internet would meet its requirement that a physician order the genetic test.
That has been a grey area among regulators and policy-makers, says Kathy Hudson, director of the Genetics and Public Policy Center at Johns Hopkins University in Washington DC. “Is a doctor who is your personal physician, who has a fiduciary responsibility to you, the same as a company doctor? Is it really the same thing to call up a company who is trying to sell you a product and have their doctor, who receives a pay-cheque from them, advise you? To me, it is not the same thing.”
The Californian law does not prevent state-based companies from marketing the tests to consumers residing outside the state. But a muddle of different state laws across the United States provides a confusing array of regulations on the issue.
New York's Department of Public Health has sent similar letters to 26 companies since last November. In response, 23andme and Navigenics have submitted business plans that the department is reviewing, says its spokesman Jeffrey Hammond. “The good news for both 23andme and Navigenics is the labs they are proposing they use for their lab work are known to the department and have a history of compliance with us.” Hammond adds: “Our goal is not to levy fines. It is to bring companies who want to do business in New York into compliance with state law.”
Hudson says that the California and New York letters point out the conspicuous lack of unifying federal regulation of genetic testing. The law “is very inconsistent from state to state at a time when the risks to consumers do not vary state to state — and when we have businesses that are certainly operating state to state”.
Ryan Phelan, chief executive of DNA Direct, says that the one-size-fits-all approach of the letters is a cause for concern, because tests being offered range from those predicting serious diseases to “fun to know” information with no bearing on a person's health. “There is going to be increasingly a need for nuanced regulation. All genetic tests should not be considered the same.”
Genome-wide association studies all the rage
This month's Nature Reviews Genetics (vol. 9, July 2008) and an upcoming conference sponsored by The Wellcome Trust on the genomics of common diseases highlight a growing trend in genetics -- genome-wide association studies (GWAS). Thanks to improvements in high-throughput sequencing, medical researchers can now scan and scout through the entire genome looking for clues to the inheritance of disease.
According to the NIH, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. Whole genome information, when combined with clinical and other phenotype data, offers the potential for increased understanding of basic biological processes affecting human health, improvement in the prediction of disease and patient care, and ultimately the realization of the promise of personalized medicine.
In addition, rapid advances in understanding the patterns of human genetic variation and maturing high-throughput, cost-effective methods for genotyping are providing powerful research tools for identifying genetic variants that contribute to health and disease.
In concert with the growth of GWAS's, a new national database has been founded. dbGaP (Database of Genotypes and Phenotypes) was developed by the National Center for Biotechnology Information (a division of the National Library of Medicine of the NIH) to archive and distribute the results of studies that have investigated the interaction of genotype and phenotype. dbGaP will serve as the NIH GWAS data repository.
Psychiatric genetics: progress amid controversy
Margit Burmeister et al.
Nature Reviews Genetics 9, 527-540 (July 2008)
* Most psychiatric disorders are highly heritable, yet few reproducible genetic risk factors have been identified by linkage analysis and candidate gene or genome-wide association studies.
* Large genomic rearrangements have been found in a subset of patients with autism and schizophrenia, suggesting that recurrent and/or new mutations are involved in psychiatric disorders.
* Several confirmed genetic risk factors of relevance to psychiatric disorders are with endophenotypes — that is, with quantitative phenotypes related to psychiatric disorders — rather than with diagnoses themselves.
* The incorporation of environmental risk factors into analysis has helped to elucidate and identify some genetic risk factors. Longitudinal studies will be needed to identify gene-by-environment effects.
* Psychiatric symptoms have a role in some Mendelian disorders that have known causes.
* Unique families with rare syndromes have led to the identification of some common genetic risk variants.
* The genetics of psychiatric disorders is complex and needs to be approached from several angles. It is therefore insufficient to focus only on linkage and association studies of clinical categories.
* Increased sample size and meta-analyses of large existing studies might allow the identification of common risk variants of psychiatric disorders.
* Future work will need to incorporate additional factors: alternative phenotypes; recurrent new mutations and rare, 'private' mutations that are not detectable by genome-wide association; the interaction of environment with genetic risk factors; and, by bioinformatic means, our growing knowledge of expression differences and biological pathways.
Genomics, like Medicine, Slow
When It Comes to Women
Read All About It--The First Female Genome! Or Is It?
Martin Enserink
Science 6 June 2008:
Vol. 320. no. 5881, p. 1274
Last week's announcement that scientists had finally sequenced the genome of a woman was hailed as a victory for equality. But it raised eyebrows as well, because the data have not been put in the public domain nor analyzed, let alone published.
This time it's personal
Nature 453, 697 (5 June 2008)
Editorial
The next head of the US National Human Genome Research Institute will need to be equipped to deal with the scientific, political and societal challenges presented by the burgeoning era of personal genomics.
On 28 May, Francis Collins announced that he is stepping down after 15 years as head of the US National Human Genome Research Institute (NHGRI), where he helped lead the international effort to sequence the entire human genetic code (see page 710). His departure is an opportunity to take stock of his legacy and to contemplate the future of the institute he leaves at a crossroads in its existence.
Collins took up his post in 1993, four years before the NHGRI became a separate branch of the National Institutes of Health (NIH) in Bethesda, Maryland. He proved to have a rare combination of political acumen, scientific talent and administrative skill — abilities that allowed him to steer the institute through numerous challenges and reinventions while remaining about as well-liked as it's possible for an institute director to be.
In the 1990s, for example, successful completion of the public arm of the Human Genome Project was in doubt until Collins rallied its members to respond to a challenge led by Craig Venter, a former NIH scientist who was mounting a sequencing effort for commercial purposes. After the genome project was successfully concluded in 2003, some in Washington began asking whether the NHGRI was still needed. Collins made the case — rightly — that the post-genomic era would be even more exciting and challenging than the race to sequence the genome. He and the NHGRI helped prove that by launching a variety of follow-on efforts, including the International HapMap Project, ENCODE (the Encyclopedia of DNA Elements) and, most recently, the 1,000 Genomes Project — an attempt to create an atlas of human genetic variation in unprecedented detail.
The National Human Genome Research Institute may become more of a target for politicians who feel it has run its course.
Those initiatives have been possible because of technological improvements that dramatically cut the cost of sequencing — improvements for which Collins deserves considerable credit, as he made them funding priorities. The lower costs have accelerated efforts worldwide to clarify the genetic basis of evolution by filling out the 'tree of life'; more than 100 non-human species have been or are now being sequenced.
Collins also deserves credit for making the ethical, legal and social issues of genomics a high priority at the NHGRI. He says he is particularly satisfied with recent passage through Congress of the Genetic Information Nondiscrimination Act, for which he had long been a passionate advocate. Certainly the passage was timely: cheaper sequencing has ushered in a new era of 'personal genomics', in which companies are offering all manner of tests that claim to reveal a person's susceptibility to conditions such as Alzheimer's disease.
Although Collins says he has no concrete plans for after he steps down on 1 August, speculation is rife that he could serve as NIH director or White House science adviser in the next presidential administration. In the meantime, the future of the NHGRI is more cloudy than his own. The funding situation at the NIH has been gloomy for years, with flat budgets stifling many potentially worthy projects. And with Collins gone, the NHGRI may become more of a target for politicians who feel it has run its course.
Ideally, then, Collins's successor will display both his scientific and political skills. He or she will have to continue to pursue ambitious new projects on the scale of 1,000 Genomes. At the same time, the new director will have to ensure that the implications and applications of those projects are fully explained to all concerned, from the medical profession and insurance companies to politicians and the public. Genomics is now at a point where the science and technology are moving much faster than society's ability to assimilate and make sense of the information. Bridging this gap — a task at which Collins worked very hard — will be his successor's major challenge.
Senate Protects Confidentiality
of Personal Genetic Data
Measure would bar use of information by insurers, employers
Baltimore Sun
April 25, 2008
By Jonathan D. Rockoff
WASHINGTON - Coming to grips with the growing role of genetic testing in American life, Congress acted yesterday to outlaw the use of genetic information in employment or insurance decisions.
The Senate approved a measure, which the House of Representatives is expected to ratify and President Bush to sign, that would become the first federal law dealing with the growing role of genetics in the prediction, diagnosis and individualized treatment of disease.
Many patients who could benefit have refused genetic testing out of fear of discrimination, experts say . . . Read article.
Paleo-Eskimo mtDNA Genome Reveals Matrilineal Discontinuity in Greenland
M. Thomas et al.
Published Online May 29, 2008
Science DOI: 10.1126/science.1159750
The Paleo-Eskimo Saqqaq and Independence I cultures, documented from archaeological remains in Northern Canada and Greenland, represent the earliest human expansion into the New World’s northern extremes. However, their origin and genetic relationship to later cultures is unknown. We sequenced a mitochondrial genome from a Paleo-Eskimo human, using 3400- to 4500-year-old frozen hair excavated from an early Greenlandic Saqqaq settlement. The sample is distinct from modern Native Americans and Neo-Eskimos, falling within haplogroup D2a1, a group previously observed among modern Aleuts and Siberian Sireniki Yuit. This suggests that the earliest migrants into the New World’s northern extremes derived from populations in the Bering Sea area, and were neither directly related to Native Americans nor the later Neo-Eskimos that replaced them.
This was the first near-complete ancient mtDNA genome ever published.
Rare Northern Israeli Population
Provides Window into Dim Genetic Past
The Druze: A Population Genetic Refugium of the Near East
Liran I. Shlush et al.
Phylogenetic mitochondrial DNA haplogroups are highly partitioned across global geographic regions. A unique exception is the X haplogroup, which has a widespread global distribution without major regions of distinct localization.
Principal Findings
We have examined mitochondrial DNA sequence variation together with Y-chromosome-based haplogroup structure among the Druze, a religious minority with a unique socio-demographic history residing in the Near East. We observed a striking overall pattern of heterogeneous parental origins, consistent with Druze oral tradition, together with both a high frequency and a high diversity of the mitochondrial DNA (mtDNA) X haplogroup within a confined regional subpopulation. Furthermore demographic modeling indicated low migration rates with nearby populations.
Conclusions
These findings were enabled through the use of a paternal kindred based sampling approach, and suggest that the Galilee Druze represent a population isolate, and that the combination of a high frequency and diversity of the mtDNA X haplogroup signifies a phylogenetic refugium, providing a sample snapshot of the genetic landscape of the Near East prior to the modern age.
Phylogenetic clustering of mtDNA haplogroups has been found to correlate with geography, such that different haplogroups often correspond to specific geographic origins [1]. For example, the L haplogroup is a hallmark of the African continent, where almost 95% of the inhabitants belong to the different lineages of this mtDNA haplogroup. Haplogroup L can also be found at low frequencies in other regions of the world due to migration events. Similarly, haplogroups A and B are predominantly found among Native Americans[1]. Haplogroup X is one of the exceptions to this pattern of limited geographical distribution, and is found at low frequencies among West Eurasians[2], northern groups of Native Americans[3], as well as in northern Africa and the Near East[4]. A very high global genetic diversity has been reported for haplogroup X[4].
Haplogroup X is further divided into two subclades. Subhaplogroup X1 was found to be largely restricted to the Afro-Asiatic-speaking populations of northern Africa and the neighboring areas, suggesting a possible geographic diffusion of X1 along the coast of the Mediterranean and the Red Sea. Subhaplogroup X2 is characterized by a much wider geographic range, but at the same time by very low frequencies in the populations of the regions where it is found[4]. No population or geographic region has been identified to date, in which haplogroup X and its major subhaplogroups are found at both high frequency and high diversity, which could provide a potential clue as to their geographic origin. Here we suggest that the Druze population of northern Israel may represent just such a population.
The Druze population has a unique historical, social and demographic structure, which is closely connected with their religion. The contemporary Druze population constitutes a small minority in four countries of the Near East: Syria, Lebanon, Israel and Jordan. In total, the estimated population number is fewer than 1,000,000 in the Near East and fewer than 100,000 in the Druze Diaspora. The Israeli Druze population is estimated at 150,000, and is distributed over three geographical subregions: the Carmel, the Galilee, and the Golan Heights. It has been postulated according to historical records that the origin of the Druze in each of these regions is different. Although the Druze represent a small percentage of the total population of the countries of the Near East in which they reside, their concentration in mountainous districts has produced a compact social structure, resulting in a nearly exclusive majority in some geographical regions, and therefore a low frequency of admixture with other populations. Druze customs strongly favor marriage within the same village or the same geographical area[5]. This social structure has turned the Druze into transnational isolates – a population which remains genetically isolated largely through the social practice of endogamy and consanguinity, despite being found in the midst of larger population majorities in multiple nationalities or countries[6]. Furthermore, unlike other monotheistic religions, the Druze tenets strictly close their religion to new adherents, thus forbidding admixture with other populations.
Previous studies described a high frequency with a low diversity of both the X1 and X2 subhaplogroups in the Druze population[4], [7]. This was attributed to a founder effect, genetic drift, and population expansion[4]. These explanations contradict Druze oral traditions, which claim that while the religion was revealed at the time of the “Dawa” (1017 A.C.E.), its adherents came from heterogeneous ancestral origins dating back further in antiquity. We sought to resolve this apparent contradiction, and at the same time re-examine the overall mtDNA and Y-chromosome diversity using a sampling strategy which might be more appropriate for the social structure and marriage practices of the Druze population. In so doing, we uncovered an unexpectedly high diversity of Druze X-haplogroup lineages, which together with its high frequency suggest that this population provides a glimpse into the past genetic landscape of the Near East, at a time when the X haplogroup was more prevalent.
Did Humans Marry or Kill Neanderthals
And Other Humanoids They Encountered?
"Genetic evidence and the modern human origins debate"
J H Relethford
Heredity (2008) 100, 555–563, published online 5 March 2008
A continued debate in anthropology concerns the evolutionary origin of 'anatomically modern humans' (Homo sapiens sapiens). Different models have been proposed to examine the related questions of (1) where and when anatomically modern humans first appeared and (2) the genetic and evolutionary relationship between modern humans and earlier human populations. Genetic data have been increasingly used to address these questions. Genetic data on living human populations have been used to reconstruct the evolutionary history of the human species by considering how global patterns of human variation could be produced given different evolutionary scenarios. Of particular interest are gene trees that reconstruct the time and place of the most recent common ancestor of humanity for a given haplotype and the analysis of regional differences in genetic diversity. Ancient DNA has also allowed a direct assessment of genetic variation in European Neandertals. Together with the fossil record, genetic data provide insight into the origin of modern humans. The evidence points to an African origin of modern humans dating back to 200 000 years followed by later expansions of moderns out of Africa across the Old World. What is less clear is what happened when these early modern humans met preexisting 'archaic human' populations outside of Africa. At present, it is difficult to distinguish between a model of total genetic replacement and a model that includes some degree of genetic mixture.
China Divided into North and South
Through Mitochondrial DNA Lineages
A spatial analysis of genetic structure of human populations in China reveals distinct difference between maternal and paternal lineages
Fuzhong Xue et al.
European Journal of Human Genetics (2008) 16, 705–717; published online 23 January 2008
Abstract
Analyses of archeological, anatomical, linguistic, and genetic data suggested consistently the presence of a significant boundary between the populations of north and south in China. However, the exact location and the strength of this boundary have remained controversial. In this study, we systematically explored the spatial genetic structure and the boundary of north–south division of human populations using mtDNA data in 91 populations and Y-chromosome data in 143 populations. Our results highlight a distinct difference between spatial genetic structures of maternal and paternal lineages. A substantial genetic differentiation between northern and southern populations is the characteristic of maternal structure, with a significant uninterrupted genetic boundary extending approximately along the Huai River and Qin Mountains north to Yangtze River. On the paternal side, however, no obvious genetic differentiation between northern and southern populations is revealed.
New directions in the anthropology of migration and multiculturalism
Steven Vertovec
Ethnic and Racial Studies, Volume 30, Number 6, November 2007, pp. 961-978(18)
Abstract
It is a kind of boom time for the anthropology of migration. Anthropologists are currently studying a wide range of migration-related topics. Many of them, of course, are not entirely new: anthropologists have been researching migration dynamics and impacts since at least the 1930s (most notably within the Manchester School of anthropology). Since the 1970s the discipline's burgeoning interst in ethnicity has largely entailed research on post-migration communities. Since the 1990s, migrant transnationalism has become one of the most fashionable topics. There is still much to do in research and theory around migration, not least with regard to public debates around multiculturalism. This introduction suggests a number of possible new directions for anthropological inquiry into migration and multiculturalism, and summarizes the special issue's contributing articles in light of their contributions toward moving the discipline in these directions.
Questions Answered, Raised
About Siberian Origins
Of Earliest Native Americans
Mitochondrial Genome Diversity in Arctic Siberians, with Particular Reference to the EvolutionaryHistory of Beringia and Pleistocenic Peopling of the Americas
Natalia V. Volodko et al.
Abstract
Through extended survey of mitochondrial DNA (mtDNA) diversity in the Nganasan, Yukaghir, Chuvantsi, Chukchi, Siberian Eskimos, and Commander Aleuts, we filled important gaps in previously unidentified internal sequence variation within haplogroups A, C, and D, three of five (AD and X) canonical mtDNA lineages that defined Pleistocenic extension from the Old to the New World. Overall, 515 mtDNA samples were analyzed via high-resolution SNP analysis and then complete sequencing of the 84 mtDNAs. A comparison of the data thus obtained with published complete sequences has resulted in the most parsimonious phylogenetic structure of mtDNA evolution in Siberia-Beringia. Our data suggest that although the latest inhabitants of Beringia are well genetically reflected in the Chukchi-, Eskimo-Aleut-, and Na-Dene-speaking Indians, the direct ancestors of the Paleosiberian-speaking Yukaghir are primarily drawn from the southern belt of Siberia when environmental conditions changed, permitting recolonization the high arctic since early Postglacial. This study further confirms that (1) Alaska seems to be the ancestral homeland of haplogroup A2 originating in situ approximately 16.0 thousand years ago (kya), (2) an additional founding lineage for Native American D, termed here D10, arose approximately 17.0 kya in what is now the Russian Far East and eventually spread northward along the North Pacific Rim. The maintenance of two refugial sources, in the Altai-Sayan and mid-lower Amur, during the last glacial maximum appears to be at odds with the interpretation of limited founding mtDNA lineages populating the Americas as a single migration.
The $1,000 Genome . . . and Beyond
"Massively parallel" instruments and novel computational algorithms are the next generation beyond traditional PCR high-throughput DNA sequencing. Month by month, they are bringing down the cost and heightening the possibilities of exploring one's complete genome. Expect a wave of commercial next-generation DNA tests as the new technology bumps down.
Read "The Impact of Next-Generation Sequencing Technology on Genetics" by Elaine R. Mardis in Trends in Genetics 24/3:133-41.
Dating of Seaweed in Chile Confirms
Oldest Inhabitants of Americas Came by Sea
Monte Verde: Seaweed, Food, Medicine, and the Peopling of South America
Tom D. Dillehay C. Ramírez, M. Pino,M. B. Collins, J. Rossen, J. D. Pino-Navarro
Science 9 May 2008:
Vol. 320. no. 5877, pp. 784 - 786
The identification of human artifacts at the early archaeological site of Monte Verde in southern Chile has raised questions of when and how people reached the tip of South America without leaving much other evidence in the New World. Remains of nine species of marine algae were recovered from hearths and other features at Monte Verde II, an upper occupational layer, and were directly dated between 14,220 and 13,980 calendar years before the present (~12,310 and 12,290 carbon-14 years ago). These findings support the archaeological interpretation of the site and indicate that the site's inhabitants used seaweed from distant beaches and estuarine environments for food and medicine. These data are consistent with the ideas that an early settlement of South America was along the Pacific coast and that seaweeds were important to the diet and health of early humans in the Americas.
Nature Reviews Genetics introduces series "Fundamental Concepts in Genetics"
Published so far are the following two:
Linkage disequilibrium — understanding the evolutionary past and mapping the medical future
Montgomery Slatkin
Heritability in the genomics era — concepts and misconceptions
Peter M. Visscher, William G. Hill & Naomi R. Wray
April 2008 Volume 9 No 4
Link
Out of sequence: how consumer genomics could displace clinical genetics
Morris W. Foster & Richard R. Sharp
Nature Reviews Genetics 9, 419 (June 2008)
Done well, examining one's genome can be an extra medical surveillance practice that has some preventive value and is complementary to traditional forms of health surveillance and patient care. As such, commercial genomic services can advance the aims of personalized medicine by providing a truly individualized approach to defining health-promoting behaviours. Rather than choose to ignore or over-regulate consumer genomics, we should work constructively with commercial providers to develop standards and practices suitable to their role as the front end of what could be a continuum of personalized health awareness and care.
Maybe We Were . . . Wrong?
Principal component analysis of genetic data
By David Reich, Alkes L Price and Nick Patterson
Nature Genetics 40/5 (2008) 491-2
Principal component analysis (PCA) has been a useful tool for analysis of genetic data, particularly in studies of human migration. A new study finds evidence that the observed geographic gradients, traditionally thought to represent major historical migrations, may in fact have other interpretations.
Is it necessary to assume an apartheid-like social structure in Early Anglo-Saxon England?
John E. Pattison
Proceedings of the Royal Society of the Biological Sciences
Published online April 22, 2008
Abstract
It has recently been argued that there was an apartheid-like social structure operating in Early Anglo-Saxon England. This was proposed in order to explain the relatively high degree of similarity between Germanic-speaking areas of northwest Europe and England. Opinions vary as to whether there was a substantial Germanic invasion or only a relatively small number arrived in Britain during this period. Contrary to the assumption of limited intermarriage made in the apartheid simulation, there is evidence that significant mixing of the British and Germanic peoples occurred, and that the early law codes, such as that of King Ine of Wessex, could have deliberately encouraged such mixing. More importantly, the simulation did not take into account any northwest European immigration that arrived both before and after the Early Anglo-Saxon period. In view of the uncertainty of the places of origin of the various Germanic peoples, and their numbers and dates of arrival, the present study adopts an alternative approach to estimate the percentage of indigenous Britons in the current British population. It was found unnecessary to introduce any special social structure among the diverse Anglo-Saxon people in order to account for the estimates of northwest European intrusion into the British population.
Read article.
Scientists reshape Y chromosome haplogroup tree gaining new insights into human ancestry
Wednesday, April 2, 2008 – The Y chromosome retains a remarkable record of human ancestry, since it is passed directly from father to son. 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.
Human cells contain 23 pairs of chromosomes: 22 pairs of autosomes, and one pair of sex chromosomes. Females carry a pair of X chromosomes that can swap, or recombine, similar regions of DNA during meiosis. However, males harbor one X chromosome and one Y chromosome, and significant recombination between these dissimilar sex chromosomes does not occur. Therefore, the non-recombining region of the Y chromosome (NRY) remains largely unchanged over many generations, directly passed from father to son, son to grandson, and so on, along with genetic variations in the NRY that may be present. Scientists can use genetic variations, such as single nucleotide polymorphisms (SNPs), on the Y chromosome as markers of human ancestry and migration.
In 2002, the Y Chromosome Consortium (YCC) constructed a tree of 153 haplogroups based upon 243 unique genetic markers. In this report, researchers led by Dr. Michael Hammer of the University of Arizona recognized the need to revisit the Y chromosome haplogroup tree and incorporate the latest data. “The YCC effort in 2002 was a landmark in mapping the then known 300 or so Y-linked SNPs on a single tree, and getting the community to use the same nomenclature system,” explains Hammer. “The rate of SNP discovery has continued to increase over the last several years, as are publications on Y chromosome origins and affinities. While this new information is useful, ironically it also brings with it the danger of introducing more chaos into the field.”
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. “The major lineages within the most common African haplogroup, E, are now all sorted out, with the topology providing new interpretations on the geographical origin of ancient sub-clades,” describes Hammer. “When one polymorphism formerly described as unique, but recently shown to have reversed was replaced by recently reported markers, a sub-haplogroup of haplogroup O, the most common in China, was considerably rearranged,” explains Fernando Mendez, a co-author of the study.
In addition to improving the resolution of branches, the latest reconstruction of the tree allows estimates of time to the most recent common ancestor of several haplogroups. “The age of [haplogroup] DE is about 65,000 years, just a bit younger than the other major lineage to leave Africa, which is assumed to be about 70,000 years old,” says Hammer, describing an example of the fine resolution of age that is now possible. “Haplogroup E is older than previously estimated, originating approximately 50,000 years ago.”
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.”
“More SNPs are being discovered, and we anticipate the rate to increase with the 1000 Genomes Project,” says Hammer, referring to the wealth of human genetic variation data that will soon be available. While this report represents a significant advance in mapping ancestry by Y chromosome polymorphisms, it is certain that future discoveries will necessitate continual revisions to the Y chromosome haplogroup tree, helping to further elucidate the mystery of our origins.
Scientists from the University of Arizona (Tuscon, AZ) and Stanford University (Stanford, CA) contributed to this study.
This work was supported by the Salus Mundi Foundation.
Media contacts:
Michael Hammer, Ph.D., has agreed to be contacted by email for more information (mfh@u.arizona.edu).
About the article:
The manuscript will be published online ahead of print on April 2, 2008. Its full citation is as follows:
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.
Where Did European Men Come From?
Kalevi Wiik
Journal of Genetic Genealogy 4 (2008) 35-85
Ten Y chromosome haplogroups are studied with 17 maps showing spread and frequencies, including R1a, R1b, N, G, I, J, E3b.
Read or download.
The Dawn of Human Matrilineal Diversity
Doron M. Behar et al.
The American Journal of Human Genetics, April 2008
Abstract
The quest to explain demographic history during the early part of human evolution has been limited because of the scarce paleoanthropological record from the Middle Stone Age. To shed light on the structure of the mitochondrial DNA (mtDNA) phylogeny at the dawn of Homo sapiens, we constructed a matrilineal tree composed of 624 complete mtDNA genomes from sub-Saharan Hg L lineages. We paid particular attention to the Khoi and San (Khoisan) people of South Africa because they are considered to be a unique relic of hunter-gatherer lifestyle and to carry paternal and maternal lineages belonging to the deepest clades known among modern humans. Both the tree phylogeny and coalescence calculations suggest that Khoisan matrilineal ancestry diverged from the rest of the human mtDNA pool 90,000-150,000 years before present (ybp) and that at least five additional, currently extant maternal lineages existed during this period in parallel. Furthermore, we estimate that a minimum of 40 other evolutionarily successful lineages flourished in sub-Saharan Africa during the period of modern human dispersal out of Africa approximately 60,00070,000 ybp. Only much later, at the beginning of the Late Stone Age, about 40,000 ybp, did introgression of additional lineages occur into the Khoisan mtDNA pool. This process was further accelerated during the recent Bantu expansions. Our results suggest that the early settlement of humans in Africa was already matrilineally structured and involved small, separately evolving isolated populations.
The success of the genome-wide association approach: a brief story of a long struggle
By Ku Chee Seng and Chia Kee Seng
European Journal of Human Genetics (2008) 16, 554–564, published online 20 February 2008
The genome-wide association approach has been the most powerful and efficient study design thus far in identifying genetic variants that are associated with complex human diseases. This approach became feasible as the result of several key advancements in genetic knowledge, genotyping technologies, statistical analysis algorithms and the availability of large collections of cases and controls. With all these necessary tools in hand, many genome-wide association studies were recently completed, and many more studies which will explore the genetic basis of various complex diseases and quantitative traits are soon to come. This approach has started to reap the fruits of its labor over the past several months. Publications of genome-wide association studies in several complex diseases such as inflammatory bowel disease, type-2 diabetes, breast cancer and prostate cancer have been abundant in the first half of this year. The aims of this review are firstly, to provide a timely summary for most of the genome-wide association studies that have been published until June/July 2007 and secondly, to evaluate to what extent these results have been validated in subsequent replication studies.
Second Generation DNA Tests
Reveal More Than Just Identity
Washington Post
Sunday, April 20, 2008; Page A01
A report in the Washington Post by Rick Weiss suggests that "second generation" forensic DNA tests, just like second generation ancestry tests, can do much more than just identify a person. They can yield information on someone's health and even their emotions.
Read DNA Tests Offer Deeper Examination Of Accused
Editorial in Nature Cautions
Against Too Much Regulation
In Genetic Testing Industry
Nature 452, 666 (10 April 2008) |
Ready or not
Transparency and honesty are essential if the genetic-testing industry is to live up to its potential.
Navigenics, a California start-up company with solid backing, launched its flagship product this week. The Health Compass, a US$2,500 genetic test, is being offered to consumers directly, over the Internet. It will scan DNA from a customer's saliva sample for a host of tiny variations and pronounce on the person's risk of developing 18 common medical conditions, including heart attack, prostate cancer and type 2 diabetes.
Why now? Because, as the company says in its corporate literature, "the science is ready. Genetic testing is ready to enter into common health-care practice."
Certainly genetic testing is here, ready or not. In the past year, genome-wide association studies have begun to pour out of labs, linking the blips in our genetic make-up to risks of developing particular medical conditions. Whether people would or could change their behaviour to ameliorate these risks remains unclear. But the ink on the research papers is barely dry before companies unveil commercial versions of the tests. Navigenics is simply the most recent; others include high-profile players such as 23andMe in Mountain View California (see Nature 450, 11; 2007) and the Icelandic genomics company deCODE Genetics. They also encompass smaller operations such as Philadelphia-based Smart Genetics, which last month offered a genetic assessment of the risk of Alzheimer's disease. Rarely have basic discoveries morphed into a commercial product quite so swiftly.
Following almost as quickly are the concerns being raised about the use of such tests. Many of these worries have been around for some time, but now that the tests are here, these discussions have taken on a new urgency. If consumers are to reap the benefits that genetic testing can offer, they need understandable information about the basis, validity and limitations of the tests. One proposed structure for providing this information is a publicly accessible registry into which test-makers would be required to upload data about their tests and the studies that back them. This information should be updated as genetic risks are changed or refined, as inevitably they will be.
Such a registry should be international, harmonizing information in what will doubtless be an industry without borders. This approach seems preferable to stepped-up regulation by agencies such as the Food and Drug Administration (FDA), which — in addition to travelling at the snail's pace of bureaucracy rather than the lightning speed of burgeoning markets — could easily have the effect of driving less-than-desirable players underground, where sub-standard tests will remain as easy to buy as black-market DVDs.
Many critics would say that a hands-off approach by the FDA is irresponsible. But on what basis should genetic tests be treated any differently from others done in government-certified clinical labs? Many of these tests — including almost all of those done by labs in-house, rather than sent out to patients and doctors as kits — are not required to demonstrate clinical utility on a test-by-test basis. For that matter, why should genetic tests be treated differently from medical devices such as MRI scanners, which were left by the FDA to prove their utility and clinical validity to physicians and providers in the marketplace, rather than in pre-market assessments?
It would be naive to suggest that transparency will solve all problems, or to assume that the marketplace will separate the wheat from the chaff with unfailing accuracy and efficiency. But to advocate relatively light regulation does not mean turning a blind eye to the risks of such a strategy. It means taking seriously the presumption that people should be free to inform themselves and make their own choices, and that by doing so they may benefit not just themselves but also the overall pace of innovation. Should it become clear that the system is allowing harm, then enhanced regulation will be appropriate.
It is also worth noting that the scientists who have driven this revolution need to assume a prominent role in ensuring that its benefits are not mishandled. Those who start companies, or advise them, can and must lead the way in ensuring that their enterprises are transparent and valid. In the meantime, online shoppers who buy genetic tests would do well to keep asking themselves whether the science is, indeed, ready.
DNA from Human Coprolites in Oregon
Strongest Proof Yet of Pre-Clovis Date
For Human Presence in North America
M. Thomas et al.
Published Online April 3, 2008, in
Science DOI: 10.1126/science.1154116
ABSTRACT
The timing of the first human migration into the Americas and its relation to the appearance of the Clovis technological complex in North America ca. 11-10.8 thousand radiocarbon years before present (14C ka B.P.) remains contentious. We establish that humans were present at Paisley 5 Mile Point Caves, south-central Oregon, by 12,300 14C yr. B.P., through recovery of human mtDNA from coprolites, directly dated by accelerator mass spectrometry. The mtDNA corresponds to Native American founding haplogroups A2 and B2. The dates of the coprolites are>1000 14C years earlier than currently accepted dates for the Clovis-complex.
"This . . . is the best evidence that humans were living in North America 14,000 years ago, a millennium before the Clovis people, long thought to be the first Americans," said one commentator on the Web.
Recreational genomics? Dreams and fears on genetic susceptibility screening
European Journal of Human Genetics (2008) 16, 403–404
GertJan B van Ommen and Martina C Cornel
With the advent of direct-to-the-consumer genetic screening and personalized genomics, a host of health care policy questions arise. "Genomic health care has the potential to reduce aggregate cost of health care by enabling better preventive strategies, but calls for a health-care system that is not fragmented. The emergence of individualized medicine is a compelling reason to deliver universal health care."
Read editorial.
Reconstructing the phylogeny of African mitochondrial DNA lineages in Slavs
Malyarchuk BA, Derenko M, Perkova M, Grzybowski T, Vanecek T, Lazur J.
European Journal of Human Genetics advance online publication 9 April 2008
Abstract
To elucidate the origin of African-specific mtDNA lineages, revealed previously in Slavonic populations (at frequency of about 0.4%), we completely sequenced eight African genomes belonging to haplogroups L1b, L2a, L3b, L3d and M1 gathered from Russians, Czechs, Slovaks and Poles. Results of phylogeographic analysis suggest that at least part of the African mtDNA lineages found in Slavs (such as L1b, L3b1, L3d) appears to be of West African origin, testifying to an opportunity of their occurrence as a result of migrations to Eastern Europe through Iberia. However, a prehistoric introgression of African mtDNA lineages into Eastern Europe (approximately 10 000 years ago) seems to be probable only for European-specific subclade L2a1a, defined by coding region mutations at positions 6722 and 12903 and detected in Czechs and Slovaks. Further studies of the nature of African admixture in gene pools of Europeans require the essential enlargement of databases of African complete mitochondrial genomes.
Ed. Note: African mitochondrial lineages in Eastern European populations could help explain Sub-Saharan African matches for Ashkenazi Jews in OmniPop. Another factor may be male haplogroup E3b, a common Jewish paternal lineage. Both incursions are so ancient as to be virtually meaningless for ethnotyping, however.
DNA Consulting Renamed
DNA Testing Systems
Inks Agreement with DNAPrint Genomics, Moves Offices to Scottsdale, Arizona
SCOTTSDALE, Ariz. – (March 11, 2008) – DNA Testing Systems, previously of Santa Fe, N.M., and formerly named DNA Consulting, has signed an agreement to sell DNAPrint Genomics’ line of biogeographical ancestry tests and has moved its offices to Scottsdale, Ariz.
DNAPrint Genomics was one of the first DNA testing companies to be formed in an industry now estimated to be worth over $150 million in consumer sales. It was launched in Sarasota, Florida, in 1997 to commercialize the biogeographical, and proprietary, genetic markers developed from the work of Mark Shriver, a biogenetics professor at Pennsylvania State University.
DNA Testing was a spin-off from the research of founder Donald N. Yates into the Jewish and American Indian genetics of a rare Appalachian ethnic group called Melungeons, a family background to which he belongs. “I had to start my own company to understand my own unusual DNA test results,” Yates said. “And then I was doing so many consultations for Melungeon cousins that I decided to commercialize my sideline and get paid for what I was doing.”
Donald Yates of DNA Testing
Yates moved his business from Savannah, Ga., where he was a professor, to Santa Fe, N.M., in 2004 and has now settled in Scottsdale, where he hopes one day to retire. The company uses genomics laboratories in Salt Lake City, Utah; Richmond, Calif., and Sarasota, Fla.
DNA Testing sells DNAPrint® tests through a large web presence, marketing them as Whole DNA, a test that estimates percentages of American Indian and other admixture; EurasianDNA, which divides a customer’s DNA into four regions of Eurasia, and EuroDNA 2.0, the newest ancestry test from DNAPrint. EuroDNA 2.0 uses discoveries in genetic markers and human migration to determine an individual’s proportion of ancestry in five parts of Europe, including the Iberian Peninsula.
According to Yates, “We are finding that many people who think they are exclusively English, Irish and Scottish have a large element of Spanish and Portuguese ancestry they did not suspect.” One reason, he said, was that the British Isles were settled chiefly by a people very much like the Basques after the last Ice Age.
Of the handful of DNA testing companies in the United States, DNA Testing is the only one that specializes in customized and personalized reports. “We’re rather boutique-like in our approach,” said Yates, “and probably want to keep it that way.” In addition to biogeographical DNA tests, the company also sells traditional paternity, Y chromosome (male) and mitochondrial (female-passed DNA) tests.
For more information, visit DNA Testing at www.dnaconsultants.com or call toll free 1-877-473-5155.
The phylogeny of the four pan-American MtDNA haplogroups: implications for evolutionary and disease studies
By A. Achilli et al.
PLoS ONE. 2008 Mar 12;3(3):e1764
ABSTRACT
Only a limited number of complete mitochondrial genome sequences belonging to Native American haplogroups were available until recently, which left America as the continent with the least amount of information about sequence variation of entire mitochondrial DNAs. 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. The derived clades are overall starlike with coalescence times ranging from 18,000 to 21,000 years (with one exception) using the conventional calibration. The average of about 19,000 years somewhat contrasts with the corresponding lower age of about 13,500 years that was recently proposed by employing a different calibration and estimation approach. Our estimate indicates a human entry and spread of the pan-American haplogroups into the Americas right after the peak of the Last Glacial Maximum and comfortably agrees with the undisputed ages of the earliest Paleoindians in South America. In addition, the phylogenetic approach also indicates that the pathogenic status proposed for various mtDNA mutations, which actually define branches of Native American haplogroups, was based on insufficient grounds.
Dwarf Race of Humans Discovered on Pacific Island
PLoS One 10.1371/journal.pone.0001780 (2008)
As reported by Brooks Hanson, diminutive fossils of Homo sapiens, perhaps representing several tens of individuals, have been found in two caves in Palau. The fossils, described by Berger et al., range in age from about 3000 to 1500 years; humans are thought to have arrived on the island from the Philippines (700 km to the west) about 1000 years earlier. The fossils include several complete, small crania still encased in flowstone. Preliminary measurements suggest a brain size near the low end of extant Homo sapiens and close to that of Homo erectus. Measurements of multiple postcranial bones imply a corresponding body size comparable to those of the smallest known H. sapiens and the early hominin Lucy. Although many traits are consistent with H. sapiens, some fossils also exhibit more primitive traits, including minimal chins and an enlarged brow ridge. These traits and some aspects of the teeth and the small body size are similar to those seen in the older, enigmatic diminutive fossils found recently on the nearby island of Flores, which in turn have been ascribed to a relict population of an earlier Homo species. Although any relation between these fossils is not clear, the sample on Palau is further evidence of the extremes in size and characteristics that may develop in isolated island human populations.
These fossils could correspond to widespread legends around the Pacific of a pygmy race of humans that retreated into the mountains as the first Polynesians arrived.
According to critics, however, the skeletons may be those of children in a mass grave.