Newsletter #15

Senate Protects 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


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.



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.

The Late Pleistocene Dispersal of Modern Humans in the Americas
Ted Goebel et al.

When did humans colonize the Americas? From where did they come and what routes did they take? These questions have gripped scientists for decades, but until recently answers have proven difficult to find. Current genetic evidence implies dispersal from a single Siberian population toward the Bering Land Bridge no earlier than about 30,000 years ago (and possibly after 22,000 years ago), then migration from Beringia to the Americas sometime after 16,500 years ago. The archaeological records of Siberia and Beringia generally support these findings, as do archaeological sites in North and South America dating to as early as 15,000 years ago. If this is the time of colonization, geological data from western Canada suggest that humans dispersed along the recently deglaciated Pacific coastline. There was another dispersal several thousand years later responsible, perhaps, for the Clovis Culture.

(Ed. Note: While this theory can account for the majority of lineages studied today among American Indians, it cannot explain the high incidence of mitochondrial haplogroups B or X, which are not found in Mongolia or Siberia in significant amounts.)

Beyond Out of Africa

Jun Z. Li et al.

Science 22 February 2008:
Vol. 319. no. 5866, pp. 1100 - 1104

Human genetic diversity is shaped by both demographic and biological factors and has fundamental implications for understanding the genetic basis of diseases. We studied 938 unrelated individuals from 51 populations of the Human Genome Diversity Panel at 650,000 common single-nucleotide polymorphism loci. Individual ancestry and population substructure were detectable with very high resolution. The relationship between haplotype heterozygosity and geography was consistent with the hypothesis of a serial founder effect with a single origin in sub-Saharan Africa. In addition, we observed a pattern of ancestral allele frequency distributions that reflects variation in population dynamics among geographic regions. This data set allows the most comprehensive characterization to date of human genetic variation.

Read extensive discussion on Dienekes' Anthropology Blog.

Y-chromosome diversity characterizes the Gulf of Oman

Alicia M Cadenas et al.

European Journal of Human Genetics (February 2008) 16, 374–386

Arabia has served as a strategic crossroads for human disseminations, providing a natural connection between the distant populations of China and India in the east to the western civilizations along the Mediterranean. To explore this region's critical role in the migratory episodes leaving Africa to Eurasia and back, high-resolution Y-chromosome analysis of males from the United Arab Emirates (164), Qatar (72) and Yemen (62) was performed. The role of the Levant in the Neolithic dispersal of the E3b1-M35 sublineages is supported by the data, and the distribution and STR-based analyses of J1-M267 representatives points to their spread from the north, most likely during the Neolithic. With the exception of Yemen, southern Arabia, South Iran and South Pakistan display high diversity in their Y-haplogroup substructure possibly a result of gene flow along the coastal crescent-shaped corridor of the Gulf of Oman facilitating human dispersals. Elevated rates of consanguinity may have had an impact in Yemen and Qatar, which experience significant heterozygote deficiencies at various hypervariable autosomal STR loci.


Check Out Heredity's Free Podcast Series

Each month Elli Leadbeater and Steve Le Comber present a free audio show. The podcast features interviews with the people behind the science and a digest of breaking news from Heredity editor Richard Nichols at Queen Mary University of London.

Fly in the Ointment of Evolutionary Theory?

Featured in January's episode is H.-J. Bandelt of the University of Hamburg, a leading statistician in the area of population genetics. His commentary on mutation rates, "Clock debate: when times are a-changin': Time dependency of molecular rate estimates: tempest in a teacup," appeared in Heredity, vol. 100, in February 2008. According to Bandelt, many current studies on the molecular clock use outmoded data and confused models to arrive at their conclusions regarding human evolution and ancient migrations. Experts do not always distinguish between hot spots in DNA sequences and an average rate of mutation. They may base their suppositions about changes in coding regions (genes) on variation in non-coding regions such as the control loop in mitochondrial DNA. For these reasons, many of our theories about time to coalescence of genetic types may be essentially flawed. Bandelt mentions the model of Amerind migration as an example.

You can subscribe to the service and receive the latest episode in your email or browse the archives. Listen to the podcast now.

Iceland's deCODE Sharpens Image

"Backed by years of experience deCODE has created the most complete genetic map of the human genome and has an unrivalled track record in mapping and validating disease genes for common and complex diseases." Such is the hype in genomics giant deCODE's new advertising campaign. How much is science and how much is marketing? Judge for yourself by going to their website. Here's more: "deCODE is also leveraging its expertise in human genetics and integrated drug discovery and development capabilities to offer innovative products and services in DNA-based diagnostics, bioinformatics, genotyping, structural biology, drug discovery and clinical development."

Cousin Marriages Produce More Children

Science 8 February 2008:
Vol. 319. no. 5864, pp. 813 - 816

An Association Between the Kinship and Fertility of Human Couples

Agnar Helgason et al.

Previous studies have reported that related human couples tend to produce more children than unrelated couples but have been unable to determine whether this difference is biological or stems from socioeconomic variables. Our results, drawn from all known couples of the Icelandic population born between 1800 and 1965, show a significant positive association between kinship and fertility, with the greatest reproductive success observed for couples related at the level of third and fourth cousins. Owing to the relative socioeconomic homogeneity of Icelanders, and the observation of highly significant differences in the fertility of couples separated by very fine intervals of kinship, we conclude that this association is likely to have a biological basis.


Female Perogative
Male Presumption

Science 25 January 2008:
Vol. 319. no. 5862

Female choice is thought to drive evolution through sexual selection. It has been assumed that females over time would show consistent preferences for the same male traits. However, Chaine and Lyon (p. 459; cover) found in a long-term study of sexual selection in lark buntings that females have flexible patterns of choice for male traits over several years. This finding explains both the stability of traits under sexual selection and the evolution of multiple male sexual signals. Analyses of phenotypic selection with short time frames can lead to incorrect predictions about the trajectory of sexual selection, which might explain earlier contradictory findings.

DNA SEQUENCING:
A Plan to Capture Human Diversity in 1000 Genomes

Jocelyn Kaiser

Science 25 January 2008:
Vol. 319. no. 5862, p. 395

Over the next 3 years, an international team plans to create a massive new catalog containing the complete genome sequences of 1000 individuals. It will help fill out the list of new genetic markers for common diseases that came out in 2007.


BREAKTHROUGH OF THE YEAR:
Human Genetic Variation

Elizabeth Pennisi

Science 318/5858 (21 December 2007) 1842-43.

Equipped with faster, cheaper technologies for sequencing DNA and assessing variation in genomes on scales ranging from one to millions of bases, researchers are finding out how truly different we are from one another. Read article .


Genetics News Highlight of 2007
According to the Editors of Nature

First whole human genome decoded

James Watson, co-discoverer of the structure of DNA, and genomics pioneer Craig Venter announced that their full genomes had been sequenced. The achievements were the first in an anticipated wave of personal-genome sequencing and crucial steps towards personalized medicines tailored to an individual's genetic makeup. Watson's genome, announced in June, was analysed by Connecticut company 454 Life Sciences' new rapid-sequencing technique. Venter's, published in September, was the first fully sequenced diploid genome — detailing DNA inherited from both parents — and revealed that human genetic variation is greater than previously thought.

In November, Google-backed Californian biotech firm 23andMe launched a $1,000 personal genome service; the same month that Icelandic deCODE genetics offered DNA testing for disease-linked genes for the same price. And 2007 saw a splurge of research papers from genome-wide disease-association studies, including diabetes and cancer.

New Evolution Textbook Receives Good Review

A textbook covering all aspects of evolution puts the spotlight on the molecular motor that drives it.

Evolution, by Nicholas H. Barton, Derek E. G. Briggs, Jonathan A. Eisen, David B. Goldstein & Nipam H. Patel

Cold Spring Harbor Laboratory Press: 2007. 833 pp. $100

Keeping pace with change

A review by Daniel Hart

Textbooks in evolutionary biology have generally kept pace with [recent] changes and several excellent books are available. This new one by Barton and colleagues is among the best. The production quality is superb in layout, composition, typesetting, colour palette, illustrations and gorgeous half-tones; and the writing is excellent, as one might expect from such a stellar cast of experts in population genetics, palaeontology, human genetics, bacterial genomics and developmental biology (respectively).

The book is in four parts. The first is a history of evolutionary thinking and evidence for the evolutionary process, which clarifies common misconceptions about evolution and rebuts 'intelligent design'. The latter is unfortunately necessary in the United States, where people who think that space aliens have landed on Earth outnumber those who believe in the darwinian theory of human evolution by about 3:1.

Part I also includes an excellent introduction to molecular biology, although I suspect that much of this duplicates what most students already know. Part II, on the origin and diversification of life, is up to date with discussions on the last universal common ancestor, as well as being an outstanding introduction to evo-devo. Part III comprises about half the book and deals with the genetic mechanisms of evolution, including speciation, in a treatment that is fresh, thorough and professional. Subtle concepts, including Fisher's geometrical theory of adaptation and the coalescent, are clearly described with minimal mathematics. The final section is devoted to human diversity and evolution, and includes an engaging discussion of human nature.

This book may not fit every instructor's needs. Some may prefer a different balance of origin, diversity, molecular evolution, population genetics and human evolution, or they may need a textbook written at a different level. But every instructor should examine this book and make an individual decision.

Turkish Population Not as Asian as You May Think

Alu insertion polymorphisms and an assessment of the genetic contribution of Central Asia to Anatolia with respect to the Balkans

Ceren Caner Berkman et al.

American Journal of Physical Anthropology (online early) 10.1002

From Dieneke's Anthropology Blog: "In the evolutionary history of modern humans, Anatolia acted as a bridge between the Caucasus, the Near East, and Europe. Because of its geographical location, Anatolia was subject to migrations from multiple different regions throughout time. The last, well-known migration was the movement of Turkic speaking, nomadic groups from Central Asia. They invaded Anatolia and then the language of the region was gradually replaced by the Turkic language. . . . Together with the data compiled from other databases, the similarity of the Anatolian population to that of the Balkans and Central Asia has been visualized by multidimensional scaling method. Analysis suggested that, genetically, Anatolia is more closely related with the Balkan populations than to the Central Asian populations. . . . In the present study, the Central Asian contribution to Anatolia was estimated as 13%. This was the lowest value among the populations analyzed."

Other genetic surveys have estimated the incidence of Central Asian genes in Eastern Europe as only 3%.


Is Evolution Itself Evolving?

Not the notion of evolution, which of course is always changing, but the reality of evolution and the genetic mutations underpinning it. Are mutations in humans increasing?

Yes, according to John Hawks et al. in "Recent Acceleration of Human Adaptive Evolution" published online December 17 in PNAS 10/1073.

Want to know more? Read an explanation by Razib in the blog Gene Expression.

Genomics sizes up

China launches large-scale human sequencing initiative

Jane Qiu & Erika Check Hayden

Published online 16 January 2008 in Nature 451, 234

Next-generation human genomics has arrived. The first large-scale whole-genome sequencing project has now begun in China, and an international multi-genome sequencing programme is hot on its heels.

The Yanhuang Project, which will sequence the entire genomes of 100 Chinese individuals over 3 years was announced by the Beijing Genomics Institute (BGI) on 8 January. Ye Jia, a spokeswoman for the project, said that once it is completed, the BGI aims to sequence the genomes of thousands more people, including ethnic groups from other Asian countries.

And a large international project, which aims to sequence the genomes of close to 1,000 individuals, is expected to be formally unveiled by the US National Institutes of Health in Bethesda, Maryland, and the Wellcome Trust Sanger Institute in Cambridge, UK, later this week. As yet it doesn't have a name, but is informally called the '1,000 genomes' project and the 'Multigenome project'. It will probably include the hundreds of individuals who participated in the International HapMap Project — an ongoing study of genetic diversity — as well as hundreds of other individuals.

The BGI will also participate in the 1,000 genomes project, says director Yang Huanming. However, only participants who meet the ethics and consent rules decided on by the international collaboration will be able to join that study, he says.

The projects usher in what many scientists think will be a new era of large-scale genomics — made possible with rapid-sequencing technologies — that will lead to more powerful comparisons between and within populations. Last year, scientists Craig Venter and James Watson became the first to release their complete individual DNA sequences. And a team led by George Church at Harvard University in Cambridge, Massachusetts, has begun the 'Personal Genome Project' that will examine portions of DNA from ten individuals who have agreed to share their information with the rest of the world.

But the Yanhuang Project — named after two emperors thought to be the ancestors of China's largest ethnic group — is the first to examine the entire genomes of private individuals. The first individual sequenced in the Yanhuang Project was a researcher; the second paid 10 million yuan (about US$1.4 million) to have his genome sequenced, Yang says. It is unclear whether such people will qualify for the international project, whose rules on confidentiality of data and the informed consent of participants may differ from China's.

Whole-genome sequencing studies are expected to deepen our scientific understanding of populations such as the Chinese, whose genetics have not been studied in great detail. The findings will inform medical research specific to those populations, and improve our understanding of human history, says Rasmus Nielsen of the University of California, Berkeley. “One of the exciting things about having so many sequences from Chinese individuals is that we will be able to say how much genetic exchange there has been between continents since [early humans migrated] out of Africa. That's been very hotly debated.”

The sequencing will allow scientists to add more detail to their maps of human diversity. The last large study of diversity, the HapMap, analysed only single-nucleotide polymorphisms, or SNPs — places in which DNA differs between two individuals by just one letter of the genetic code. This approach allows scientists to hunt for relatively common genetic variants. But the evidence linking disease to rare variants is growing, says Richard Myers, director of the Stanford Human Genome Center in Palo Alto, California. Whole-genome sequencing will improve detection of these rare variants, and offer a more complete understanding of the genetics of many human traits, he predicts.

"It's going to be very useful to sequence genomes from all populations and have large enough numbers so you can do comparisons between populations,” Myers says. “Even if you don't care about disease, it's going to help us look at human population history and phenotypes not relevant to disease, such as craniofacial structure, eye colour, hair colour and other fascinating things."


Discerning the ancestry of European Americans in genetic association studies

Alkes Price et al.

European Americans are often treated as a homogeneous group, but in fact form a structured population due to historical immigration of diverse source populations. Discerning the ancestry of European Americans genotyped in association studies is important in order to prevent false positive or negative associations due to population stratification and to identify genetic variants whose contribution to disease risk differs across European ancestries. Here, we investigate empirical patterns of population structure in European Americans, analyzing 4,198 samples from four genome-wide association studies to show that components roughly corresponding to northwest European, southeast European and Ashkenazi Jewish ancestry are the main sources of European American population structure. Building on this insight, we constructed a panel of 300 validated markers that are highly informative for distinguishing these ancestries. We demonstrate that this panel of markers can be used to correct for stratification in association studies that do not generate dense genotype data.

Get the whole article here.

mtDNA haplogroups of indigenous Mexican populations

Characterization of mtDNA haplogroups in 14 Mexican indigenous populations.

Hum Biol. 79/3 (Jun 2007)313-20

R. I. Peñaloza-Espinosa et al.

ABSTRACT: In this descriptive study we investigated the genetic structure of 513 Mexican indigenous subjects grouped in 14 populations (Mixteca-Alta, Mixteca-Baja, Otomi, Purépecha, Tzeltal, Tarahumara, Huichol, Nahua-Atocpan, Nahua-Xochimilco, Nahua-Zitlala, Nahua-Chilacachapa, Nahua-Ixhuatlancillo, Nahua-Necoxtla, and Nahua-Coyolillo) based on mtDNA haplogroups. These communities are geographically and culturally isolated; parents and grandparents were born in the community. Our data show that 98.6% of the mtDNA was distributed in haplogroups A1, A2, B1, B2, C1, C2, D1, and D2. Haplotype X6 was present in the Tarahumara (1/53) and Huichol (3/15), and haplotype L was present in the Nahua-Coyolillo (3/38). The first two principal components accounted for 95.9% of the total variation in the sample. The mtDNA haplogroup frequencies in the Purépecha and Zitlala were intermediate to cluster 1 (Otomi, Nahua-Ixhuatlancillo, Nahua-Xochimilco, Mixteca-Baja, and Tzeltal) and cluster 2 (Nahua-Necoxtla, Nahua-Atocpan, and Nahua-Chilacachapa). The Huichol, Tarahumara, Mixteca-Alta, and Nahua-Coyolillo were separated from the rest of the populations. According to these findings, the distribution of mtDNA haplogroups found in Mexican indigenous groups is similar to other Amerindian haplogroups, except for the African haplogroup found in one population.