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Friday, November 21, 2008

A couple of PCAs with Polish samples

Context is important when it comes to genetic affinity, and this is clearly illustrated by an article published in the European Journal of Human Genetics this week. For instance, on the intra-European principal component analysis (PCA) featured in this paper, Poles from Warsaw and Lodz basically sit between samples from Dresden and Moscow, but overlap more with the latter. However, when an African and two East Asian populations are added (ie. the plot turns into an inter-continental one), they end up almost at the top of a much tighter European blob, overlapping heavily with Swedes, Slovaks, Germans and Czechs, just to name a few.

Key: CEU = Utah Americans of Western and Northern European ancestry; CHB = Northern Han Chinese from Beijng; JPT = Japanese from Tokyio; YRI = Yoruba from Nigeria.

The study also shows a pairwise fixation index (Fst) table featuring 12 European, one American (CEU), one Sub-Saharan (YRI), and two East Asian (CHB and JPT) samples. Most of the results appear to align with geography, although Scandinavians show higher affinity than their southern neighbors, Germans and Poles, to the East Asians. This suggests that East Asian or East Asian-like admixture diffused into Scandinavia from the north.

Abstract: An investigation into fine-scale European population structure was carried out using high-density genetic variation on nearly 6000 individuals originating from across Europe. The individuals were collected as control samples and were genotyped with more than 300 000 SNPs in genome-wide association studies using the Illumina Infinium platform. A major East–West gradient from Russian (Moscow) samples to Spanish samples was identified as the first principal component (PC) of the genetic diversity. The second PC identified a North–South gradient from Norway and Sweden to Romania and Spain. Variation of frequencies at markers in three separate genomic regions, surrounding LCT, HLA and HERC2, were strongly associated with this gradient. The next 18 PCs also accounted for a significant proportion of genetic diversity observed in the sample. We present a method to predict the ethnic origin of samples by comparing the sample genotypes with those from a reference set of samples of known origin. These predictions can be performed using just summary information on the known samples, and individual genotype data are not required. We discuss issues raised by these data and analyses for association studies including the matching of case-only cohorts to appropriate pre-collected control samples for genome-wide association studies.

Simon C Heath et al, Investigation of the fine structure of European populations with applications to disease association studies, European Journal of Human Genetics (2008) 16, 1413–1429; doi:10.1038/ejhg.2008.210

Wednesday, November 19, 2008

Best of 2008: Corded Ware DNA from Germany

One of the biggest hits of the year for this blogger was the discovery of Y-DNA haplogroup R1a among three Corded Ware skeletons from a burial site in Eulau, eastern Germany. It's an important result, because it links one of Europe's most dominant Y-haplogroups to a major Late Neolithic archeological complex.

All three individuals were confirmed to be paternally related via their shared Y-STR haplotype. Nevertheless, the outcome appears far from a random coincidence. Consider that in Europe today R1a shows highest frequencies in Poland and Western Russia, which are both located in former Corded Ware territory, and where the Eulau R1a haplotype appears to have its closest modern matches. Moreover, the Corded Ware culture is often classified as an Indo-European culture by archeologists and linguists, while at the same time R1a has been posited as a marker of the early Indo-Europeans by some geneticists. Needless to say, I'm expecting R1a to be a common, and perhaps dominant marker among Corded Ware samples when more of them make it to the lab.

The consensus haplotype of the three individuals (based on most complete profile) gave two exact matches in in an European population sample of 11,213 haplotypes in a set of 100 populations (as of July 2008, Release ‘‘23’’ from 2008–01-15 14:44:25): one individual from Poland (1/939 from Gdansk) and one from Russia (1/48 from Tambov).


The Y haplotype was predicted using the Web-based program Haplotype Predictor (9). The three individuals of grave 99 belong to haplotype R1a, with a probability of 100% based on the Y-STR profile of individual 3 (10). To confirm haplogroup status, we further amplified an 85-bp fragment covering the Y-SNP marker SRY10831.2 characteristic for R1a (11). Primer sequences are given in Table S6. Sequences and sequenced clones from independent extract of all three individuals show the specific G to A transition identifying R1a (Fig. S5).

The mitochondrial DNA (mtDNA) lineages of the Eulau skeletons belonged to haplogroups K1b (3), X2 (2), H, I, K1a2, and U5b. Most of these maternal markers aren't particularly common in Europe today, and the overall result appears decidedly unusual compared to the mtDNA frequencies of modern European populations, largely because of the low frequency of H.

I'm quite certain this is at least partly due to the small sample size and presence of several related individuals skewing some of the frequencies. However, it's interesting to note that this pattern of discontinuity between mtDNA gene pools from different time periods has also been reported in other studies, some with larger samples, and focusing on different regions of Europe. So it might well be a signal of significant shifts in mtDNA frequencies during European prehistory and early history, possibly as a result of major migrations leading to significant population replacements.

Interestingly, one of the ancient K1b lineages most closely matched a haplotype shared by two modern Shugnans from Tajikistan. Exactly how the Corded Ware individual is related to these two Central Asians isn't clear yet, but Shugni is an Indo-Iranian language, so some kind of early Indo-European relationship is possible.


Wolfgang Haak et al, Ancient DNA, Strontium isotopes, and osteological analyses shed light on social and kinship organization of the Later Stone Age, PNAS, Published online before print November 17, 2008, doi:10.1073/pnas.0807592105