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

Bayona-Bafaluy, M. Pilar (Universidad de Zaragoza) ; López-Gallardo, Ester (Universidad de Zaragoza) ; Emperador, Sonia (Universidad de Zaragoza) ; Pacheu-Grau, David (Universidad de Zaragoza) ; Montoya, Julio (Universidad de Zaragoza) ; Ruiz-Pesini, Eduardo (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.1186/s13023-022-02428-0

Año: 2022

Publicado en: Orphanet Journal of Rare Diseases 17 (2022), 316 [4 pp.]
ISSN: 1750-1172

Factor impacto JCR: 3.7 (2022)

Categ. JCR: GENETICS & HEREDITY rank: 60 / 171 = 0.351 (2022) - Q2 - T2
Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 75 / 136 = 0.551 (2022) - Q3 - T2

Factor impacto CITESCORE: 5.8 - Medicine (Q1)

Factor impacto SCIMAGO: 1.12 - Medicine (miscellaneous) (Q1) - Pharmacology (medical) (Q1) - Genetics (clinical) (Q2)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B33-20R
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI17-00021
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI21-00229
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2019-116970GA-I00
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RYC2020-029544-I

Tipo y forma: (Published version)

Área (Departamento): Area Histología (Dpto. Anatom.Histolog.Humanas)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)