This is a fairly good paper. Many articles in the literature either date human expansions by genetic methods (which tell us about the age of common ancestors, or the accumulated genetic variation and its characteristics -e.g., linkage disequilibrium- but tell us little about where the ancestors lived), or by geo-demographic methods (which tell us about how populations grow and expand on the map given various parameter settings), or by archaeological methods (which record the spatio-temporal occurrence of sites, but are difficult to interpret and are subject to various biases).

The authors make a good point about the mess that population genetics is with respect to dating human movements, so their decision to avoid it is understandable. However, genetics will eventually be able to complement the other two approaches, by the study of ancient DNA from the different sites (whenever they are associated with human remains). So far, ancient DNA in the region has been limited to Holocene remains, which postdate the events of interest, but if 30,000 year old Kostenki can yield useful results, I don’t see why human remains from northeastern Eurasia cannot, as conditions for DNA preservation there (=cold) are good.

“Responding to a court order issued a week ago, the National Institutes of Health (NIH) on Friday ordered intramural researchers studying human embryonic stem cells (hESCs) to shut down their experiments. NIH’s action — probably unprecedented in its history — is a response to a preliminary injunction on 23 August from US District Judge Royce Lamberth. The judge ruled that the Obama policy allowing NIH funding to be used to study hESC lines violates a law prohibiting the use of federal funds to destroy embryos.”

There was a recent study on AIDS progression and Y-chromosome haplogroups. There is a new one on haplogroup I and coronary heart disease. I haven’t tracked down the article yet, but here is the press release from the European Society of Cardiology:

Scientists in the UK have shown that genetic variations in the Y chromosome affect a male’s risk of coronary heart disease. It is well known that males have a higher incidence of coronary heart disease than females due, in part, to the Y chromosome they inherit from their fathers. To investigate the role of the Y chromosome further, a team from the University of Leicester carried out research to determine whether genetic variations in the Y-chromosome affect risk for males.

Not all Y chromosomes are the same. There are variants within the male gender called “Y-haplogroups”, which are usually associated with specific geographic regions and tend to indicate the origin of the ancestral line. Professor Nilesh Samani explains the background to the project that was funded by the British Heart Foundation, “We set out to determine if men with differing types of Y chromosome were at differing risk of heart disease. We tested nearly 3,000 British males, and found that those carrying the I-haplogroup variant had a 55 percent higher risk of coronary heart disease.”

Of the 3,000 men tested, 1,295 were the cohort group of those with coronary heart disease and the rest were the control group. The Y-haplogroup was identified in all men, and the results showed that those in the I-haplogroup had an approximately 55 percent higher risk of coronary heart disease compared to the others. The association of the I-haplogroup with coronary heart disease was independent of, and not explained by, traditional heart risk factors such as cholesterol, high blood pressure and smoking.

Commonly found in central, eastern and northern Europe, the I-haplogroup is carried by about 13 percent of British men. Its origin is thought to be of the Gravettian culture, which arrived in Europe from the Middle East about 25,000 years ago. Since the I-haplogroup is not so prevalent in southern parts of Europe, an interesting speculation is whether it contributes to the higher levels of coronary heart disease in the north compared to the south – however, this requires further research and testing.

What is clear from this study though, is that men carrying the I-haplogroup are more likely to suffer from coronary heart disease than men with other Y-haplogroups.

With the new version of SpringerLink that runs the journal’s website you can now get citations for articles in BibTex format, for easy inclusion in new articles prepared with LaTex. From the main page you can get to article listings through the search field or links such as Online First Articles or Current Issue. Then when you click on a particular article’s title you’ll get a page with the abstract and (among other things) an “EXPORT CITATION” link. Click that and then set the options as follows:

The paper hasn’t gone live at the PNAS site as of this writing, but here is part of the press release. The abstract and my comments on the paper will be posted here (after I get through the zillion other interesting papers that the last week of August seems to have brought us):

Investigators in the laboratory of Stephen Warren, PhD, chairman of human genetics at Emory University School of Medicine, used DNA microarray technology to read variant sites across the entire genomes of 471 Ashkenazi Jews. The work comes from a collaboration between Warren and Ann Pulver, ScD, associate professor of psychiatry and behavioral sciences at Johns Hopkins University School of Medicine, who recruited the participants for a study of schizophrenia genetics.

Researchers looked for close to one million single nucleotide polymorphisms (SNPs): common alternative spellings in the genome, analogous to American and British spellings of words such as organize/organise. One measure of genetic diversity in a population is heterozygosity, or how many of the SNPs inherited from the mother and father are different; a more inbred population has less heterozygosity.

“We were surprised to find evidence that Ashkenazi Jews have higher heterozygosity than Europeans, contradicting the widely-held presumption that they have been a largely isolated group,” says first author Steven Bray, PhD, a postdoctoral fellow in Warren’s laboratory.

…

High linkage disequilibrium can come either from an isolated population (for example, an island whose residents are all descendents of shipwreck survivors) or the relatively recent mixture of separate populations. Bray and his colleagues did find evidence of elevated linkage disequilibrium in the Ashkenazi Jewish population, but were able to show that this matches signs of interbreeding or “admixture” between Middle Eastern and European populations.

The researchers were able to estimate that between 35 and 55 percent of the modern Ashkenazi genome comes from European descent.

“Our study represents the largest cohort of Ashkenazi Jews examined to date with such a high density of genetic markers, and our estimate of admixture is considerably higher than previous estimates that used the Y chromosome to calculate European admixture at between five and 23 percent,” Bray says.

…

“Only six of the 21 disease genes that we examined showed evidence of selection,” Bray says. “This supports the argument that most of the Ashkenazi-prevalent diseases are not generally being selected for, but instead are likely a result of a genetic bottleneck effect, followed by random drift.”

The new paper comes in the heels of two other papers by Behar et al. and Atzmon et al. which considered Jews in general, discovering additional clusters of Jews that were distinct from Ashkenazi Jews. As I have argued in my review of these papers, the different clusters are not the result of isolation, as the different groups of Jews do not only deviate from each other, but also in the direction of their host populations. It would be worthwhile to perform similar admixture analyses on non-AJ populations to determine what their influence from host populations is. With a little effort it would be possible to reconstruct the ancestral Jewish population, by identifying what is common in the different Jewish populations.

From the paper:

The fixation index, FST, calculated concurrently to the PCA, confirms that there is a closer relationship between the AJ and several European populations (Tuscans, Italians, and French) than between the AJ and Middle Eastern populations (Fig. S2B). This finding can be visualized with a phylogenetic tree built using the FST data (Fig. S2C), showing that the AJ population branches with the Europeans and not Middle Easterners. Two recent studies performing PCA and population clustering with high-density SNP genotyping from many Jewish Diaspora populations, both showed that of the Jewish populations, the Ashkenazi consistently cluster closest to Europeans (13, 25). Genetic distances calculated by both groups also show that the Ashkenazi are more closely related to some host Europeans than to the ancestral Levant (13, 25). Although the proximity of the AJ and Italian populations could be explained by their admixture prior to the Ashkenazi settlement in Central Europe (13), it should be noted that different demographic models may potentially yield similar principal component projections (33); thus, it is also consistent that the projection of the AJ populations is primarily the outcome of admixture with Central and Eastern European hosts that coincidentally shift them closer to Italians along principle component axes relative to Middle Easterners. Taken as a whole, our results, along with those from previous studies, support the model of a Middle Eastern origin of the AJ population followed by subsequent admixture with host Europeans or populations more similar to Europeans. Our data further imply that modern Ashkenazi Jews are perhaps even more similar with Europeans than Middle Easterners.

The bolded part reminds me of what I wrote in my review of Atzmon et al. regarding the choice of parental populations and how they affect admixture estimates. The “Middle Eastern” component estimate will increase if central and eastern Europeans are used as representative of the European admixture, while the “European” estimate will increase if Italians are used. But, the same applies to the other end of the continuum: if ancestral Jews were indeed like current Middle Easterners such as the Druze or Palestinians, but the latter may have moved (in genetic space) away from ancient Levantines due to subsequent admixture (Arabs, and in the case of Palestinians even Africans): this would reduce the inferred Middle Eastern component.

PNAS doi: 10.1073/pnas.1006538107

Resolving postglacial phylogeography using high-throughput sequencing

Kevin J. Emerson et al.

The Ashkenazi Jewish (AJ) population has long been viewed as a genetic isolate, yet it is still unclear how population bottlenecks, admixture, or positive selection contribute to its genetic structure. Here we analyzed a large AJ cohort and found higher linkage disequilibrium (LD) and identity-by-descent relative to Europeans, as expected for an isolate. However, paradoxically we also found higher genetic diversity, a sign of an older or more admixed population but not of a long-term isolate. Recent reports have reaffirmed that the AJ population has a common Middle Eastern origin with other Jewish Diaspora populations, but also suggest that the AJ population, compared with other Jews, has had the most European admixture. Our analysis indeed revealed higher European admixture than predicted from previous Y-chromosome analyses. Moreover, we also show that admixture directly correlates with high LD, suggesting that admixture has increased both genetic diversity and LD in the AJ population. Additionally, we applied extended haplotype tests to determine whether positive selection can account for the level of AJ-prevalent diseases. We identified genomic regions under selection that account for lactose and alcohol tolerance, and although we found evidence for positive selection at some AJ-prevalent disease loci, the higher incidence of the majority of these diseases is likely the result of genetic drift following a bottleneck. Thus, the AJ population shows evidence of past founding events; however, admixture and selection have also strongly influenced its current genetic makeup.

Link

The stack of exciting papers to read keeps growing. Good things come in pairs for R1b folk.

Forensic Science International: Genetics doi:10.1016/j.fsigen.2010.07.006

Strong intra- and inter-continental differentiation revealed by Y chromosome SNPs M269, U106 and U152

Fulvio Cruciani et al.

I have an opportunity to fund a research of my choosing.  Not a lot of money.  About $2,000.

Questions for the readers that have directed funded a research before:
- What research would you fund?  Which one seems most promising to you?
- $2,000 seems quite small for a research project.  How did you approach the researcher?

Other thoughts are welcome as well.