Is population frequency a useful criterion to assign pathogenicity to newly described mitochondrial DNA variants?

Population frequency has been one of the most widely used criteria to help assign pathogenicity to newly described mitochondrial DNA variants. However, after sequencing this molecule in thousands of healthy individuals, it has been observed that a very large number of genetic variants have a very lo...

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Bibliographic Details
Published in:Orphanet journal of rare diseases 2022-08, Vol.17 (1), p.1-316, Article 316
Main Authors: Bayona-Bafaluy, M. Pilar, López-Gallardo, Ester, Emperador, Sonia, Pacheu-Grau, David, Montoya, Julio, Ruiz-Pesini, Eduardo
Format: Article
Language:English
Subjects:
Amino acids
Cytochrome
DNA sequencing
Genetic diversity
Genetic research
Genetic variation
Genotype & phenotype
Identification and classification
Letter to the Editor
Medical genetics
Medical research
Mitochondrial DNA
Mutation
Oxidative phosphorylation
Pathogenicity
Pathological variants
Phenotypes
Phosphorylation
Polypeptides
Population
Population frequency
Population genetics
Proteins
Rare diseases
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Summary:Population frequency has been one of the most widely used criteria to help assign pathogenicity to newly described mitochondrial DNA variants. However, after sequencing this molecule in thousands of healthy individuals, it has been observed that a very large number of genetic variants have a very low population frequency, which has raised doubts about the utility of this criterion. By analyzing the genetic variation of mitochondrial DNA-encoded genes for oxidative phosphorylation subunits in 195,983 individuals from HelixMTdb that were not sequenced based on any medical phenotype, we show that rare variants are deleterious and, along with other criteria, population frequency is still a useful criterion to assign pathogenicity to newly described variants.
ISSN:1750-1172
1750-1172
DOI:10.1186/s13023-022-02428-0