Mitochondrial insertions/deletions (INDELs) burden in Parkinson's disease: an analysis from a Brazilian cohort.
Mitochondrial insertions/deletions (INDELs) burden in Parkinson's disease: an analysis from a Brazilian cohort.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
BR · Author affiliation · country only
Laboratory of Bioinformatics and Data Science, Institute of Biological Sciences, Federal University of Pará, 66075-110, Belém, Pará, Brazil.Location evidence
São Paulo, BR · Author affiliation
Laboratory of Energetic Metabolism, Instituto of Chemistry, Department of Biochemistry, University of São Paulo, São Paulo, 05508-000, São Paulo, Brazil.Location evidence
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Original abstract
INTRODUCTION: Mitochondrial DNA (mtDNA) alterations are increasingly associated with Parkinson's disease (PD), particularly due to their role in oxidative stress. However, the contribution of mtDNA insertions and deletions (INDELs) to PD remains poorly understood, particularly in genetically admixed populations such as Brazilians. METHODS: To explore this, we sequenced the complete mtDNA from blood samples of 179 admixed individuals from the Brazilian Amazon (104 people with PD and 75 controls). Data processing included FastQC, MultiQC, FastP, BWA, and mtDNA-Server 2. RESULTS: We identified a significantly higher burden of mtDNA INDELs in PD compared with controls in Complex I genes (OR = 9.23; 95% CI: 2.22-63.55; FDR = 0.044). Differences in heteroplasmy levels were also observed in the ATP6, ND4, and ND5 genes. Importantly, we discovered seven new PD-associated INDELs (m.13763_13763delinsCCA, m.13885_13885delinsCTG, m.13888_13890delinsT, m.13767_13769delinsC, m.13810_13812delinsG, m.13813_13813delinsGCA, and m.13764_13764delinsCAT) that are particularly more frequent among individuals harboring uniparental lineages of Native American origin. CONCLUSION: Our findings report novel mtDNA INDELs, particularly in Complex I, which may contribute to PD susceptibility and highlight the importance of investigating mitochondrial genomic variation in underrepresented populations. These associations should be interpreted as preliminary, and further longitudinal studies with independent cohorts are required to confirm these observations.