The number of non-synonymous mutations shown in S4 Table, was extracted when present only in controls and not cases with psychiatric disorders, and is shown in the row for control subjects.

<p>The number of non-synonymous mutations found only in cases (and not controls) is shown on each row for each disorder. The ratio of the number of mutations / subject was calculated for each group, and a z-score for the difference of the observed for each group compared to the entire mean was calculated. There was a significant increase in non-synonymous mutations (p = 0.024, two tailed z-score test) in persons with SZ compared to controls.</p><p>The number of non-synonymous mutations shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127280#pone.0127280.s007" target="_blank">S4 Table</a>, was extracted when present only in controls and not cases with psychiatric disorders, and is shown in the row for control subjects.</p

Novel-rare NS mutations observed in 65 DLPFC brain samples and confirmed by Sanger sequencing, the D-loop mutation is non-coding.

<p>The effect of the amino acid substitutions was determined using Polyphen.</p><p>*Once in submitted online mtDNA sequencing data.</p><p>¹ T8945C was previously reported by our group [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127280#pone.0127280.ref009" target="_blank">9</a>].</p><p>Novel-rare NS mutations observed in 65 DLPFC brain samples and confirmed by Sanger sequencing, the D-loop mutation is non-coding.</p

Electropherograms confirming heteroplasmy.

<p><b>A)</b> Heteroplasmy at the 16519 locus confirmed by Sanger sequencing and showing clear reversals of allele calls and heteroplasmy concordant with NGS calculated results. The electropherograms for D-84 are from the same subject but from two different brain regions, D-84E corresponds to DLPFC with 10% T reads and D-84J corresponds to substantia nigra SN with 0% T reads. <b>B)</b> Multiplasmy confirmed by Sanger sequencing. Electropherogram showing a psychiatric subject with 5, 6 and 7 (CA)n dinucleotide repeats at position 514 in the mtDNA displacement Loop. The actual number of repeats was determined from the individual reads from the sequencing data, 5 and 6 repeats are over-imposed in the electropherogram, consistent with the NGS results.</p

Heteroplasmy and multiplasmy in mtDNA.

<p>The heteroplasmy was calculated from NGS reads and confirmed by Sanger sequencing (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127280#pone.0127280.g001" target="_blank">Fig 1B</a>). Multiplasmic length polymorphisms were observed in the D-loop region and showed a trend for over-representation of cases at the 514 (CA)_n and the D16189 loci. <b>Multiplasmy was observed about 1.5 times more frequently in cases.</b> Note the tri-allelic multiplasmy results for two subjects (B-76 and S-114) showing 5, 6, and 7 repeat lengths shown in bold. Heteroplasmy/multiplasmy at all these six loci were also confirmed by Sanger sequencing.</p><p>*multiplasmy occurred in all brain regions sequenced.</p><p>#Val313Ile.</p><p>Heteroplasmy and multiplasmy in mtDNA.</p

Sequencing error hotspots in mtDNA.

<p>Four variant loci not previously reported showed heteroplasmic A/C transversions in a large number of samples that could not be validated by Sanger sequencing or by allele specific PCR using LNA-primers.</p><p>^<b>#</b> 121 samples were sequenced (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127280#pone.0127280.s005" target="_blank">S2 Table</a>), this column shows the number of samples with the aberrant mutations that were errors.</p><p>Sequencing error hotspots in mtDNA.</p

qPCR Confirmation of decreased expression of metallothionein subfamilies 1 and 2.

<p>Significant differences are in bold for one tailed t-test confirming the direction of the change.</p

Demographic and physiological details for the subjects included in the qPCR validation sample (cohort 2).

<p>Mean±standard deviation values (SD) are presented. DLPFC: dorsolateral prefrontal cortex, ACC: anterior cingulate cortex, NAcc: nucleus accumbens, NA: not available.</p

Expression levels of 11 metallothionein probe sets corresponding to 9 gene as measured by microarrays (HG-U133Plus 2.0) in the ACC and NAcc of non-suicide (grey bars) and suicide (black bars) mood disorder subjects.

<p>Significant genes/probe sets are labeled by * (P<0.01) and # (P<0.05) signs.</p

Canonical pathway enrichment analysis using Ingenuity.

<p><b>A</b> In the DLPFC. <b>B</b> In the ACC. <b>C</b> In the NAcc.</p