Tuesday, April 15, 2008

European population substructure...again   posted by Razib @ 4/15/2008 04:25:00 PM

The discussion continues in regards to the relationship of various West Eurasian and North African groups (i.e., Europeans, North Africans and Near Easterners). There have been several papers published within the last few years which shed some light on these questions. We've blogged them before, and I don't think that they radically alter what you might find in History and Geography of Human Genes, but I thought I'd point to them again, with a special focus on figures of note.

European Population Substructure: Clustering of Northern and Southern Populations. Figure 4 B:

Analysis and Application of European Genetic Substructure Using 300 K SNP Information, Figure 1 B & D:

Discerning the Ancestry of European Americans in Genetic Association Studies, Figure 3 A:

Analysis of genetic variation in Ashkenazi Jews by high density SNP genotyping, Figure 9:

Since these papers are all Open Access there's really no excuse to not read them (at least the "Discussion" sections). I hope people won't go around looking for charts to "prove" whatever pet hypothesis they want to promote, the population-level classifications we generate often have only an approximate relationship to the multi-dimensional shape of human genetic variation at the finer-grained level. Note that some of these principal component charts really don't have that many individuals typed, and you may wonder about the representativeness of the samples of their putative national populations. Though these are important points, I do think we need to be cautious about our expectations in regards to the sort information we're going to extract on the margins as the N increases and the individuals typed come from every region of a nation. I suspect we'll get more oddities like the Etruscans as isolated or peculiar populations are included in these samples, and the exceptions to the broad patterns tell us a lot about the details of human history. But, I doubt we'll overturn the general shape of the relationships and clinal gradients we see here.

Addendum: I somewhat played down the future surprises that these sorts of fine grained analyses might have for us...but I do want to note that the studies will continue. That's because they aren't done for the purposes of elucidating human genetic history as such, rather, the primary rationale is to highlight substructure which might be relevant when attempting to ascertain disease relevant alleles. In the medical context then there may be significant returns on the investment here which I don't want to underestimate. If, for example, a particular drug's efficacy within the African American population in the United States is directly proportional to the makeup of one's ancestry then identifying ancestry-informative markers is very useful.

Update: Measuring European Population Stratification with Microarray Genotype Data, Figure 1 A: