Detailed analysis of a 1.1 Mb genomic region surrounding the <i>VKORC1</i> gene locus in East Asia.

<p>The boundaries of the region displayed (chr16:30,271,572-31,391,123; UCSC human genome build hg18) were chosen so as to include the three clusters of significant scores detected in East Asia by the selection tests in the 2 Mb region centered on <i>VKORC1</i> (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053049#pone-0053049-g003" target="_blank">Figure 3</a>). (<b>A</b>) <b>Name and location of genes.</b> Exons are displayed as blue boxes and the transcribed strand is indicated with an arrow. Genes located in the block of strong LD encompassing <i>VKORC1</i> and including the SNPs in the red box shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053049#pone-0053049-g004" target="_blank">Figure 4C</a>, are highlighted in the grey area. (<b>B</b>) <b>XP-EHH results in East Asia.</b> The significance of the XP-EHH scores (−log₁₀ empirical <i>p</i>-value) are shown for individual SNPs with a MAF ≥0.01 in East Asia. Horizontal dashed lines indicate 0.05 and 0.01 chromosome-wide significance levels. Recombination hotspots detected in HapMap Phase II data are indicated by red vertical dotted lines. The data and methods used to derive these hotspots are available from the HapMap website (<a href="http://www.hapmap.org/" target="_blank">http://www.hapmap.org/</a>) <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053049#pone.0053049-McVean1" target="_blank">[83]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053049#pone.0053049-Winckler1" target="_blank">[84]</a>. (<b>C</b>) <b>LD plot.</b> Pairwise LD values, depicted as <i>D</i>’, are shown for SNPs with a MAF ≥0.01 in East Asia. <i>D</i>’ values are displayed in different colors from yellow to red for <i>D</i>’ = 0 to <i>D</i>’ = 1, respectively. The red box highlights SNPs included in the LD block encompassing <i>VKORC1.</i> The plot was produced using the snp.plotter R package <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0053049#pone.0053049-Luna1" target="_blank">[74]</a>.</p

Atypical patterns of genetic differentiation observed for <i>VKORC1</i> SNPs.

<p>Genome-wide empirical distributions of <i>F_ST</i> values were constructed from 644,143 SNPs having a MAF ≥0.001 at the global level. Individual values of <i>F_ST</i> calculated for each of the seven <i>VKORC1</i> SNPs are plotted against their global MAF. The functional rs9923231 SNP is shown in red. The 50^th, 95^th and 99^th percentiles are indicated as dotted, dashed and full red lines, respectively.</p

Distribution of –log₁₀ (<i>p-</i>values) for four selection tests across a 2 Mb region centered on <i>VKORC1</i>.

<p>A black vertical line indicates the physical position of <i>VKORC1</i> on chromosome 16. Horizontal red dotted and dashed lines show 0.05 and 0.01 chromosome-wide significance levels, respectively. The selection tests (inter-regional <i>F_ST</i>, XP-CLR, XP-EHH and iHS, respectively) were separately applied in each of the seven geographic regions.</p

Results of the inter-regional <i>F_ST</i>, intra-regional <i>F_ST</i>, XP-EHH and iHS tests in the seven geographic regions.

a<p>Derived allele frequency estimated at the global level.</p>b<p><i>F_ST</i> estimated at the inter-regional level, <i>i.e.</i> between a given geographic region and the remaining ones.</p>c<p><i>P</i>-values are derived from the genome-wide empirical distribution of <i>F_ST</i> values.</p>d<p><i>F_ST</i> estimated at the intra-regional level, <i>i.e.</i> among populations within a region.</p>e<p><i>P</i>-values are derived from the empirical distribution of the iHS and XP-EHH scores along the chromosome 16.</p>*<p><i>p</i><0.05; ** <i>p</i><0.01; *** <i>p</i><0.005.</p><p>NA: Not Applicable (for iHS: when a gap>200 kb between successive SNPs is found in the region in the region delimited by the SNPs where the EHH value drops below 0.05 around the core SNP).</p