Lao Oscar, Altena Eveline, Becker Christian, Brauer Silke, Kraaijenbrink Thirsa, van Oven Mannis, Nürnberg Peter, de Knijff Peter, Kayser Manfred
Department of Forensic Molecular Biology, Erasmus MC University Medical Center Rotterdam, P,O, Box 2040, Rotterdam 3000 CA, Netherlands.
Investig Genet. 2013 May 20;4(1):9. doi: 10.1186/2041-2223-4-9.
The presence of a southeast to northwest gradient across Europe in human genetic diversity is a well-established observation and has recently been confirmed by genome-wide single nucleotide polymorphism (SNP) data. This pattern is traditionally explained by major prehistoric human migration events in Palaeolithic and Neolithic times. Here, we investigate whether (similar) spatial patterns in human genomic diversity also occur on a micro-geographic scale within Europe, such as in the Netherlands, and if so, whether these patterns could also be explained by more recent demographic events, such as those that occurred in Dutch population history.
We newly collected data on a total of 999 Dutch individuals sampled at 54 sites across the country at 443,816 autosomal SNPs using the Genome-Wide Human SNP Array 5.0 (Affymetrix). We studied the individual genetic relationships by means of classical multidimensional scaling (MDS) using different genetic distance matrices, spatial ancestry analysis (SPA), and ADMIXTURE software. We further performed dedicated analyses to search for spatial patterns in the genomic variation and conducted simulations (SPLATCHE2) to provide a historical interpretation of the observed spatial patterns.
We detected a subtle but clearly noticeable genomic population substructure in the Dutch population, allowing differentiation of a north-eastern, central-western, central-northern and a southern group. Furthermore, we observed a statistically significant southeast to northwest cline in the distribution of genomic diversity across the Netherlands, similar to earlier findings from across Europe. Simulation analyses indicate that this genomic gradient could similarly be caused by ancient as well as by the more recent events in Dutch history.
Considering the strong archaeological evidence for genetic discontinuity in the Netherlands, we interpret the observed clinal pattern of genomic diversity as being caused by recent rather than ancient events in Dutch population history. We therefore suggest that future human population genetic studies pay more attention to recent demographic history in interpreting genetic clines. Furthermore, our study demonstrates that genetic population substructure is detectable on a small geographic scale in Europe despite recent demographic events, a finding we consider potentially relevant for future epidemiological and forensic studies.
欧洲人类遗传多样性存在从东南向西北的梯度分布，这是一个已被充分证实的现象，最近全基因组单核苷酸多态性（SNP）数据也证实了这一点。传统上，这种模式是由旧石器时代和新石器时代主要的史前人类迁徙事件来解释的。在这里，我们研究人类基因组多样性中（类似的）空间模式是否也出现在欧洲的微观地理尺度上，比如在荷兰，如果是这样，这些模式是否也可以用更近的人口事件来解释，比如荷兰人口历史上发生的那些事件。
我们使用全基因组人类SNP Array 5.0（Affymetrix），新收集了总共999名荷兰个体的数据，这些个体在荷兰全国54个地点采样，涉及443,816个常染色体SNP。我们通过使用不同遗传距离矩阵的经典多维尺度分析（MDS）、空间祖先分析（SPA）和ADMIXTURE软件来研究个体遗传关系。我们进一步进行了专门分析以寻找基因组变异中的空间模式，并进行了模拟（SPLATCHE2）以对观察到的空间模式进行历史解读。
我们在荷兰人群中检测到了一个微妙但明显的基因组群体亚结构，可区分出东北部、中西部、中北部和南部群体。此外，我们观察到荷兰各地基因组多样性分布存在从东南向西北的统计学显著梯度，这与欧洲其他地区早期的发现类似。模拟分析表明，这种基因组梯度同样可能是由荷兰历史上的古代事件以及更近的事件造成的。
考虑到荷兰存在遗传不连续性的有力考古证据，我们将观察到的基因组多样性渐变模式解释为荷兰人口历史上近期而非古代事件所致。因此，我们建议未来的人类群体遗传学研究在解释遗传渐变时更多地关注近期人口历史。此外，我们的研究表明，尽管有近期人口事件，但在欧洲的小地理尺度上仍可检测到遗传群体亚结构，我们认为这一发现可能与未来的流行病学和法医学研究相关。
