<i>CYP2B6</i> variants predicting aberrant exon 7-9 splicing, generating the SV9 and λMP1 splice-forms, versus correct exon 7-8 splicing, individually or in an optimum multivariate model.

a<p>Difference in PCR cycle time (ΔCt) determined by subtracting the Ct value of the PCR reaction using primers ‘7/8F’ and ‘9R’ from the Ct value of the PCR reaction using primers ‘7/9F’ and ‘9R’ (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-g004" target="_blank">Figure 4</a>, primer sequences in table S4).</p

The ratio of aberrant exon 3-3A/B splicing (generating the SV2-5 splice-forms) to all transcripts that include exons 2, 3 & 4.

<p>The difference in PCR cycle times (ΔCt) for cDNAs for (n) liver biopsy samples divided by rs3745274 (<i>CYP2B6*6</i>) and rs3786552 genotype, as dictated by the optimum model predicting ΔCt (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-t004" target="_blank">Table 4</a>). Relative expression, ΔCt, was determined by subtracting the Ct value of the PCR reaction using primers ‘2/3F’ and ‘4R’ from the Ct value of the PCR reaction using primers ‘2/3F’ and ‘3/3AB R’ (Fig. 4). The boxplot provides a summary of the data distribution. The box represents the interquartile range, which includes 50% of values. The line across the box indicates the median. The whisker lines extend to the highest and lowest values that are within 1.5x the interquartile range. Further outliers are marked with circles.</p

<i>CYP2B6</i> variants predicting aberrant exon 7-8A splicing, generating the λMP8 splice-form, versus correct exon 7-8 splicing, individually or in an optimum multivariate model.

a<p>Difference in PCR cycle time (ΔCt) determined by subtracting the Ct value of the PCR reaction using primers ‘7/8F’ and ‘9R’ from the Ct value of the PCR reaction using primers ‘7/8A F’ and ‘9R’ (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-g004" target="_blank">Figure 4</a>, primer sequences in table S4).</p

<i>CYP2B6</i> variants predicting aberrant exon 3-3A/B splicing, generating the SV2-5 splice-forms, versus all transcripts that include exons 2, 3 & 4, individually or in an optimum multivariate model.

a<p>Difference in PCR cycle time (ΔCt) determined by subtracting the Ct value of the PCR reaction using primers ‘2/3F’ and ‘4R’ from the Ct value of the PCR reaction using primers ‘2/3F’ and ‘3/3AB R’ (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-g004" target="_blank">Figure 4</a>, primer sequences in table S4).</p

Common <i>CYP2B6</i> splice-forms, and the relative locations of primers used in quantitative real-time splice-form expression assays.

<p>Splice form nomenclature follows prior literature <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone.0079700-Hofmann1" target="_blank">[27]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone.0079700-Lamba1" target="_blank">[28]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone.0079700-Miles1" target="_blank">[38]</a>. The locations of common non-synonymous variants are marked on the full-length transcript. Not to scale.</p

The ratio of aberrant exon 7-9 splicing (generating the SV9/λMP1 splice-forms) to correct exon 7-8 splicing.

<p>The difference in PCR cycle times (ΔCt) for cDNAs for (n) liver biopsy samples divided by rs3745274 (<i>CYP2B6*6</i>) genotype, as dictated by the optimum model predicting ΔCt (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-t006" target="_blank">Table 6</a>). Relative expression, ΔCt, was determined by subtracting the Ct value of the PCR reaction using primers ‘7/8F’ and ‘9R’ from the Ct value of the PCR reaction using primers ‘7/9F’ and ‘9R’ (Fig. 4). The boxplot provides a summary of the data distribution. The box represents the interquartile range, which includes 50% of values. The line across the box indicates the median. The whisker lines extend to the highest and lowest values that are within 1.5x the interquartile range. Further outliers are marked with circles.</p

The ratio of allele-specific gene expression (ΔCt) for cDNAs from rs3211371 (<i>CYP2B6*5</i>) heterozygous liver biopsy samples.

<p>Samples, excluding rs2279343 heterozygotes, are either heterozygous (CT) at rs8100458 (C/*5, n = 5), or rs8100458 TT homozygotes (T/*5, n = 4). ΔCt differs significantly by genotype (p = 0.025). Relative expression, ΔCt, was determined by subtracting the smaller Ct value of one allele PCR reaction from the larger Ct value of the other allele PCR reaction normalized against the average ratio obtained from gDNAs for each genotype. The boxplot provides a summary of the data distribution. The box represents the interquartile range, which includes 50% of values. The line across the box indicates the median. The whisker lines extend to the highest and lowest values that are within 1.5x the interquartile range. Further outliers are marked with circles.</p

<i>CYP2B6</i> haplotypes in metabolism experiment.

<p>Polymorphic sites analyzed are given at the top of each column by rs number, gene position and further relevant description. Haplotypes are ordered by common allele name and frequency in the COGEND metabolism dataset.</p

The ratio of aberrant exon 3-7 splicing (generating the SV1 splice-form) to correct exon 6-7 splicing.

<p>The difference in PCR cycle times (ΔCt) for cDNAs for (n) liver biopsy samples divided by rs3745274 (<i>CYP2B6*6</i>) genotype, as dictated by the optimum model predicting ΔCt (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-t003" target="_blank">Table 3</a>). Relative expression, ΔCt, was determined by subtracting the Ct value of the PCR reaction using primers ‘6/7F’ and ‘7R’ from the Ct value of the PCR reaction using primers ‘3/7F’ and ‘7R’ (Fig. 4). The boxplot provides a summary of the data distribution. The box represents the interquartile range, which includes 50% of values. The line across the box indicates the median. The whisker lines extend to the highest and lowest values that are within 1.5x the interquartile range. Further outliers are marked with circles.</p

The ratio of aberrant exon 7-8A splicing (generating the λMP8 splice-form) to correct exon 7-8 splicing.

<p>The difference in PCR cycle times (ΔCt) for cDNAs for (n) liver biopsy samples divided by rs3745274 (<i>CYP2B6*6</i>) genotype, as dictated by the optimum model predicting ΔCt (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0079700#pone-0079700-t007" target="_blank">Table 7</a>). Relative expression, ΔCt, was determined by subtracting the Ct value of the PCR reaction using primers ‘7/8F’ and ‘9R’ from the Ct value of the PCR reaction using primers ‘7/8A F’ and ‘9R’ (Fig. 4). The boxplot provides a summary of the data distribution. The box represents the interquartile range, which includes 50% of values. The line across the box indicates the median. The whisker lines extend to the highest and lowest values that are within 1.5x the interquartile range. Further outliers are marked with circles.</p