Mitochondrial polymorphisms were analyzed in PLINK for allelic association with 50,000 case-control permutations to obtain empirical p-values.

<p>The number of individuals with mtDNA alleles shown in the far right columns is from the Ingman mt database (URL <a href="http://www.genpat.uu.se/mtDB/" target="_blank">http://www.genpat.uu.se/mtDB/</a>). A preliminary odds-ratio was calculated by comparing the affected allele frequency to the Ingman database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004913#pone.0004913-Ingman1" target="_blank">[80]</a>. All case-control differences were either in the control region, or a synonymous substitution in the third position in coding regions.</p

Demographics of subjects from which DLPFC mtDNA was resequenced.

<p>All subjects had a rapid death and absence of prolonged hypoxia prior to death. An increased pH was found in MDD compared to the C group. Subjects with SZ died at younger age than C subjects. The Ct for extracted DNA was measured by qPCR for genomic DNA and was similar between groups.</p

The haplogroup determination of mtDNA derived from DLPFC was condensed from Table 1 and showed that BD and SZ were over-represented in Pre HV haplogroup and MDD was over-represented in the “other” haplogroups.

<p>The chi-square for this table is (chi-square = 13.7 (6), p = 0.032).</p

The super haplogroup (U, K, UK) showed a shift in postmortem brain pH, and this finding was significant following permutation analysis.

<p>The histogram shows the frequency of the pH (bars) for the super haplogroup (red) compared to all other matrilineages (blue). The accumulated percentage (right y-axis) is shown as two lines with the super haplogroup (red line) and all other matrilineages (blue line). There were no subjects with a prolonged death, or agonal factors as rated according to the Hardy <i>et al.</i> scale <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004913#pone.0004913-Wester1" target="_blank">[98]</a>. PMI differences did not account for this significant effect, as PMI was equivalent between the super haplogroup and other haplogroups.</p

Transition/transversion bias calculation for mtDNA coding sequences shows difference between SZ and control group substitution.

*<p><i>R</i> = [A*G*<i>k₁</i>+T*C*<i>k₂</i>]/[(A+G)*(T+C)]. Codon positions included were 1st+2nd+3rd. All calculations were conducted in MEGA4 <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004913#pone.0004913-Tamura1" target="_blank">[84]</a>.</p><p>This result is consistent with the increased synonymous substitution rate in SZ shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0004913#pone-0004913-t004" target="_blank">Table 4</a>.</p

The haplogroup determination of mtDNA derived from DLPFC showed 31 diverse haplogroups that could be reconstructed.

<p>The haplogroup determination of mtDNA derived from DLPFC showed 31 diverse haplogroups that could be reconstructed.</p

pH in postmortem brain showed significant association with three mtDNA SNPs.

<p>The empirical p-values were from PLINK with permutation. The three mtDNA SNPs define the super- haplogroup U, K, UK matrilineages. This super-haplogroup demonstrated significantly increased postmortem pH (mean 7.0±0.18 SD) compared to the other haplogroups combined (mean 6.8±0.18 SD); permuted p-value was 0.01 for 5,000 random group tests. This robust association was not altered by differences in PMI, agonal factors, or case-control assignment differences between haplogroups. The PMI was not different between the U, K, UK super haplogroup and the remaining haplogroups, and including PMI in ANCOVA did not reduce the significance of the pH differences (p = 0.0007 with PMI as a covariate).</p>*<p>The A and G columns refer to Ingman database frequencies (URL <a href="http://www.genpat.uu.se/mtDB/" target="_blank">http://www.genpat.uu.se/mtDB/</a>), while the A# and G# columns refer to observed frequencies in this study.</p

Electropherogram results for direct sequencing of the ND4L T10652C variant.

<p>(A) is the ‘T’ allele sequencing result from the lowest heteroplasmic individual used to make the ‘T’ allele clone standard for SNaPshot and allele specific PCR. (B) is the ‘C’ allele sequencing result from the highest heteroplasmic individual detected with microarray (MDD subject from haplogroup D1) used to make the ‘C’ allele clone standard.</p