Analysis of mitochondrial DNA allelic changes in Parkinson’s disease: a preliminary study

Research output: Contribution to journalArticle

Abstract

Background: Mitochondrial DNA (mtDNA) mutations are considered as a possible primary cause of age-associated neurodegenerative disorders like Parkinson’s disease (PD). Aims: To analyze, along the whole mtDNA sequence of PD patients, the presence of non-reference alleles compared to reference alleles, as defined in the revised Cambridge Reference Sequence (rCRS). Methods: mtDNA was extracted from whole blood of PD and control groups, and was sequenced using a chip-based resequencing system. Results: 58 nucleotide positions (np) exhibited a different allelic distribution in the two groups; in 81% of them the non-reference alleles were over-represented in PD patients, similar to findings reported in patients with Alzheimer’s disease, albeit in reduced proportion. Closer analysis of the 58 np in PD group showed that they were characterized by low-level heteroplasmy, and that the nucleotide substitutions determined an amino acid change in 84% of cases. Conclusions: These results suggest that mtDNA allelic changes are increased in PD and that age-related neurodegenerative diseases could share a common mechanism involving mtDNA.

Original languageEnglish
JournalAging clinical and experimental research
DOIs
Publication statusAccepted/In press - Jan 1 2019

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Mitochondrial DNA
Parkinson Disease
Nucleotides
Alleles
Neurodegenerative Diseases
Hematologic Diseases
Amino Acid Substitution
Alzheimer Disease
Control Groups
Mutation

Keywords

  • MitoChip
  • mtDNA
  • Neurodegeneration
  • Parkinson’s disease
  • Resequencing

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology

Cite this

@article{f424771ba5ad4ea9919ba8236acf67a3,
title = "Analysis of mitochondrial DNA allelic changes in Parkinson’s disease: a preliminary study",
abstract = "Background: Mitochondrial DNA (mtDNA) mutations are considered as a possible primary cause of age-associated neurodegenerative disorders like Parkinson’s disease (PD). Aims: To analyze, along the whole mtDNA sequence of PD patients, the presence of non-reference alleles compared to reference alleles, as defined in the revised Cambridge Reference Sequence (rCRS). Methods: mtDNA was extracted from whole blood of PD and control groups, and was sequenced using a chip-based resequencing system. Results: 58 nucleotide positions (np) exhibited a different allelic distribution in the two groups; in 81{\%} of them the non-reference alleles were over-represented in PD patients, similar to findings reported in patients with Alzheimer’s disease, albeit in reduced proportion. Closer analysis of the 58 np in PD group showed that they were characterized by low-level heteroplasmy, and that the nucleotide substitutions determined an amino acid change in 84{\%} of cases. Conclusions: These results suggest that mtDNA allelic changes are increased in PD and that age-related neurodegenerative diseases could share a common mechanism involving mtDNA.",
keywords = "MitoChip, mtDNA, Neurodegeneration, Parkinson’s disease, Resequencing",
author = "Tiziana Casoli and Rosamaria Lisa and Paolo Fabbietti and Fiorenzo Conti",
year = "2019",
month = "1",
day = "1",
doi = "10.1007/s40520-019-01197-4",
language = "English",
journal = "Aging clinical and experimental research",
issn = "1594-0667",
publisher = "Springer International Publishing AG",

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TY - JOUR

T1 - Analysis of mitochondrial DNA allelic changes in Parkinson’s disease

T2 - a preliminary study

AU - Casoli, Tiziana

AU - Lisa, Rosamaria

AU - Fabbietti, Paolo

AU - Conti, Fiorenzo

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Mitochondrial DNA (mtDNA) mutations are considered as a possible primary cause of age-associated neurodegenerative disorders like Parkinson’s disease (PD). Aims: To analyze, along the whole mtDNA sequence of PD patients, the presence of non-reference alleles compared to reference alleles, as defined in the revised Cambridge Reference Sequence (rCRS). Methods: mtDNA was extracted from whole blood of PD and control groups, and was sequenced using a chip-based resequencing system. Results: 58 nucleotide positions (np) exhibited a different allelic distribution in the two groups; in 81% of them the non-reference alleles were over-represented in PD patients, similar to findings reported in patients with Alzheimer’s disease, albeit in reduced proportion. Closer analysis of the 58 np in PD group showed that they were characterized by low-level heteroplasmy, and that the nucleotide substitutions determined an amino acid change in 84% of cases. Conclusions: These results suggest that mtDNA allelic changes are increased in PD and that age-related neurodegenerative diseases could share a common mechanism involving mtDNA.

AB - Background: Mitochondrial DNA (mtDNA) mutations are considered as a possible primary cause of age-associated neurodegenerative disorders like Parkinson’s disease (PD). Aims: To analyze, along the whole mtDNA sequence of PD patients, the presence of non-reference alleles compared to reference alleles, as defined in the revised Cambridge Reference Sequence (rCRS). Methods: mtDNA was extracted from whole blood of PD and control groups, and was sequenced using a chip-based resequencing system. Results: 58 nucleotide positions (np) exhibited a different allelic distribution in the two groups; in 81% of them the non-reference alleles were over-represented in PD patients, similar to findings reported in patients with Alzheimer’s disease, albeit in reduced proportion. Closer analysis of the 58 np in PD group showed that they were characterized by low-level heteroplasmy, and that the nucleotide substitutions determined an amino acid change in 84% of cases. Conclusions: These results suggest that mtDNA allelic changes are increased in PD and that age-related neurodegenerative diseases could share a common mechanism involving mtDNA.

KW - MitoChip

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KW - Neurodegeneration

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KW - Resequencing

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