Brief project description:
Background:
Mitochondrial dysfunction is increasingly implicated in the pathogenesis of multiple sclerosis (MS), yet its precise role remains unclear. This study aimed to evaluate the contribution of mitochondrial DNA (mtDNA) variation and POLG mutations to disease susceptibility and course in the Polish relapsing–remitting MS (RRMS) population.
Methods:
Whole mtDNA was sequenced in 100 RRMS patients and 212 healthy controls using NGS. We assessed the presence of pathogenic variants, distribution of haplogroups, rare variants, and heteroplasmy. Absolute mtDNA copy number was measured by real-time PCR. Additionally, patient group was screened for four common POLG mutations (p.Gly268Ala, p.Ala467Thr, p.Pro587Leu, and p.Trp748Ser).
Results:
No pathogenic variants were detected in mtDNA or the POLG gene. However, several mtDNA variants were associated with relapse occurrence, disability level, and age at symptom onset. Certain mitochondrial variants appeared protective in female patients. No significant associations were found for mtDNA haplogroups, copy number, heteroplasmy, or rare variants with MS risk or progression.
Conclusions:
Although mtDNA alterations are unlikely to be a primary causative factor of MS, they may influence disease expression and progression in the Polish population.
The dataset consists of the following zip archives and files:
_FASTQ_.zip – raw sequencing data as FASTQ files (*.fastq.gz) from next-generation sequencing (NGS) of mtDNA from persons with multiple sclerosis (MS_FASTQ_a/b/c) and control individuals (Control_group_A_FASTQ_a/b/c and Control_group_IMDIK_FASTQ_a/b). The files can be opened using CLC Genomics Workbench software, any other similar bioinformatics software, or open-source bioinformatics tools for NGS data analysis.
_SNV.xlsx – lists of mtDNA variants (SNVs and indels) identified from the bioinformatics analysis of mtDNA NGS data. The files can be opened with MS Excel or any other spreadsheet software.
File naming instructions:
FASTQ files: e.g. 16-SM001_S43_L001_R1_001.fastq.gz, 16-K1-56_S34_L001_R1_001.fastq.gz, AB-K6_S85_L001_R1_001.fastq.gz
- 16- or AB- – LR-PCR amplicon 16 kb or AB (for details, please see https://doi.org/10.1016/j.exer.2018.10.004)
- SM001_ or K1-56_ or K6_ – MS subject ID or control group A subject ID or control group IMDiK subject ID
- S43_ – Sample number based on the order of samples in the sample sheet
- L001_ – Flow cell lane number
- R1_ – Read number in paired-end sequencing run (1 or 2)
- 001 – Constant segment in FASTQ files.
