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View Full Version : Fine-scale population structure in Europe. S. Leslie, G. Hellenthal et al



Angela
01-10-14, 17:41
The paper is not yet available, but this is the abstract. (Thanks to Dienekes for publishing the abstracts from the upcoming ASHG Conference. This is the same conference where Lazaridis will be presenting his new paper on population turnover in Central Europe. I wonder if I could get in if I made a quick trip to San Diego? http://cdn.eupedia.com/forum/images/smilies/main/grin.png)



There is considerable interest in detecting and interpreting fine-scale population structure in Europe: as a signature of major events in the history of the populations of Europe, and because of the effect undetected population structure may have on disease association studies. Population structure appears to have been a minor concern for most of the recent generation of genome-wide association studies, but is likely to be important for the next generation of studies seeking associations to rare variants. Thus far, genetic studies across Europe have been limited to a small number of markers, or to methods that do not specifically account for the correlation structure in the genome due to linkage disequilibrium. Consequently, these studies were unable to group samples into clusters of similar ancestry on a fine (within country) scale with any confidence. We describe an analysis of fine-scale population structure using genome-wide SNP data on 6,209 individuals, sampled mostly from Western Europe. Using a recently published clustering algorithm (fineSTRUCTURE), adapted for specific aspects of our analysis, the samples were clustered purely as a function of genetic similarity, without reference to their known sampling locations. When plotted on a map of Europe one observes a striking association between the inferred clusters and geography. Interestingly, for the most part modern country boundaries are significant i.e. we see clear evidence of clusters that exclusively contain samples from a single country. At a high level we see: the Finns are the most differentiated from the rest of Europe (as might be expected); a clear divide between Sweden/Norway and the rest of Europe (including Denmark); and an obvious distinction between southern and northern Europe. We also observe considerable structure within countries on a hitherto unseen fine-scale - for example genetically distinct groups are detected along the coast of Norway. Using novel techniques we perform further analyses to examine the genetic relationships between the inferred clusters. We interpret our results with respect to geographic and linguistic divisions, as well as the historical and archaeological record. We believe this is the largest detailed analysis of very fine-scale human genetic structure and its origin within Europe. Crucial to these findings has been an approach to analysis that accounts for linkage disequilibrium.



They're certainly promising a lot. Unfortunately, I wasn't totally overwhelmed by the prior Hellenthal et al results. Very dodgy interpretations, in my view. This is what you get, in my opinion, when you try to infer migration flows and admixture by relying exclusively on modern dna. Here's the prior study:
http://www.sciencemag.org/content/343/6172/747

Here's Dienekes' take on it. As is often the case, he sees the issues.
http://dienekes.blogspot.com/2014/02/human-admixture-common-in-human-history.html
If that paper is any indication, I am skeptical as to what we will get in the way of interpretation. As to what it will tell us about clustering of modern populations, everything depends on the sample selection.

In that regard, I tried to find out what screening criteria was used in the prior Hellenthal study when it comes to the selection of samples. The published list of sources that I could find just says things like Southern Italian sample, or Greek sample, or West Sicilian sample, or East Sicilian sample. (Obviously, this data file is part of the current Eurogenes list of reference samples.) However, it doesn't state precise locales, and it doesn't contain what I think is the requisite claim in genetics studies, i.e. that all four grandparents of the testees are from the same location.

You would hope that academics are doing that, and I'm sure most are, but there was one widely quoted paper about Italians where the data set came from hospital records where the only information known was the place where the patient was treated! That paper belongs in a rubbish bin. This current paper is part of a Cystic Fibrosis study, so it makes me a little uneasy. I sincerely hope that they got genealogical information about these people. Otherwise, their data for Italy, at least, will be useless.

If anyone has access to the new or old paper and has info on the sampling criteria, it would be great if you could post it here.

John Doe
01-10-14, 17:45
What will this study be about? Will they use ancient DNA? I hope they'll also mention Ashkenazi Jews. :-p;-)

John Doe
01-10-14, 17:54
Oh yeah! I remember their previous study, I think, they published this map:
http://admixturemap.paintmychromosomes.com/ Unfortunately they didn't present AJs, maybe because we're mistakenly a homogeneous bunch due to the bottleneck.

Angela
01-10-14, 18:19
Oh yeah! I remember their previous study, I think, they published this map:
http://admixturemap.paintmychromosomes.com/ Unfortunately they didn't present AJs, maybe because we're mistakenly a homogeneous bunch due to the bottleneck.

You're not "mistakenly" a homogeneous bunch because of the bottleneck, you are a homogenous bunch because of the bottleneck. That's why you form your own cluster, and why you're all such close cousins of one another, and why you can't see anyone but Ashkenazim on RF on 23andme.

I would recommend the posts of MiTuCents on that site.

John Doe
01-10-14, 18:30
You're not "mistakenly" a homogeneous bunch because of the bottleneck, you are a homogenous bunch because of the bottleneck. That's why you form your own cluster, and why you're all such close cousins of one another, and why you can't see anyone but Ashkenazim on RF on 23andme.

I would recommend the posts of MiTuCents on that site.

Oh, I see. Yeah, I know MiTuCents, I read his posts. :)

Aberdeen
01-10-14, 19:31
Of course you could get into the conference, Angela. Just show them that you're a member of this forum. What other ID would you need?

The problem with making inferences about the past on the basis of localized testing, IMO, is that you have to know whether the population has been stable for a long time in that particular location or whether some event caused a major population turnover within historic times. For example, the Black Death wiped out most of the population of coastal northern Norway, and therefore during the early modern period the Norse government encouraged Sami to settle there, give up their reindeer for farming and fishing and interbreed with the few surviving locals and become culturally Norse. I would expect that event to leave a DNA footprint that might be hard to interpret correctly if you didn't know the history of the area.

John Doe
01-10-14, 19:42
The problem with making inferences about the past on the basis of localized testing, IMO, is that you have to know whether the population has been stable for a long time in that particular location or whether some event caused a major population turnover within historic times. For example, the Black Death wiped out most of the population of coastal northern Norway, and therefore during the early modern period the Norse government encouraged Sami to settle there, give up their reindeer for farming and fishing and interbreed with the few surviving locals and become culturally Norse. I would expect that event to leave a DNA footprint that might be hard to interpret correctly if you didn't know the history of the area.

I see, thanks. :)

Angela
01-10-14, 20:21
[QUOTE=Aberdeen;440488]Of course you could get into the conference, Angela. Just show them that you're a member of this forum. What other ID would you need?
:grin::grin::grin:



The problem with making inferences about the past on the basis of localized testing, IMO, is that you have to know whether the population has been stable for a long time in that particular location or whether some event caused a major population turnover within historic times. For example, the Black Death wiped out most of the population of coastal northern Norway, and therefore during the early modern period the Norse government encouraged Sami to settle there, give up their reindeer for farming and fishing and interbreed with the few surviving locals and become culturally Norse. I would expect that event to leave a DNA footprint that might be hard to interpret correctly if you didn't know the history of the area.

Exactly. Just imagine the mess that would result if they didn't even bother to make sure that the testees had all four grandparents from a certain area.

I actually read a quote from them about their prior paper stating that they deliberately didn't look at the details of the history of certain areas because they wanted to "let the genetics speak for itself", or some such twaddle, and how the genetics data is the only thing that counts.:startled: :annoyed::sad-2: Maybe that's true for ancient dna to some extent although you still have to tie it to archaeology and culture to make sense of it, but especially in terms of modern dna???? That seems kind of arrogant to me. This is the sort of thing that can give genetic population studies a bad name.

Aberdeen
01-10-14, 21:35
I imagine if you let the genetics speak for itself, it would say "That isolated mountain village has had no significant population turnover for 2000 years, but the nearby coastal village has had 17 major population turnovers during that time." Or something of that sort. Except we wouldn't hear the message. If we didn't know the history, all the genetics would tell us is that the results are confusing.

John Doe
02-10-14, 17:17
@Angela @Aberdeen Perhaps the reason so far there hasn't been full genome analysis of pre exile Jews is due to the lack of suitable corpses that yield enough DNA? Am I correct?