order for the northern group with respect to the southern group in subset analyses (Figure 2). We speculate that this observation may reflect the difference in the origins of the additional substructure in the northern group compared to the other elements of substructure in the southern group. This result suggests that overall geographic suggestions of clines based on principal components must be cautiously interpreted. Third, the PCA can be dramatically affected by differences in relatively small genomic regions that may not reflect true population substructure. This is illustrated by our finding that the second axis in the “northern” European analysis (also observed for the third axis in the entire European set) is dependent solely on a <4 Mb segment of Chromosome 8 that carries a common inversion. The effect of such an inversion on PCA is presumably due to a long stretch of linkage disequilibrium that is a result of non-recombination between the inverted and non-inverted chromosomal segments. The genomic distribution of particularly informative SNPs for each PC axis provides one method to inspect whether the apparent differences in substructure are due to a single or very limited number of genomic intervals. For the first two axes of the PCA
