The transmission of human mitochondrial DNA in four‐generation pedigrees - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Human Mutation Année : 2022

The transmission of human mitochondrial DNA in four‐generation pedigrees

Résumé

Most of the pathogenic variants in mitochondrial DNA (mtDNA) exist in a heteroplasmic state (coexistence of mutant and wild-type mtDNA). Understanding how mtDNA is transmitted is crucial for predicting mitochondrial disease risk. Previous studies were based mainly on two-generation pedigree data, which are limited by the randomness in a single transmission. In this study, we analyzed the transmission of heteroplasmies in 16 four-generation families. First, we found that 57.8% of the variants in the great grandmother were transmitted to the fourth generation. The direction and magnitude of the frequency change during transmission appeared to be random. Moreover, no consistent correlation was identified between the frequency changes among the continuous transmissions, suggesting that most variants were functionally neutral or mildly deleterious and thus not subject to strong natural selection. Additionally, we found that the frequency of one nonsynonymous variant (m.15773G>A) showed a consistent increase in one family, suggesting that this variant may confer a fitness advantage to the mitochondrion/cell. We also estimated the effective bottleneck size during transmission to be 21−71. In summary, our study demonstrates the advantages of multigeneration data for studying the transmission of mtDNA for shedding new light on the dynamics of the mutation frequency in successive generations.
Fichier principal
Vignette du fichier
Liu_Human_Mutation.pdf (1.99 Mo) Télécharger le fichier
Origine Publication financée par une institution

Dates et versions

hal-04604735 , version 1 (07-06-2024)

Licence

Identifiants

Citer

Qi Liu, Muhammad Faaras Iqbal, Tahir Yaqub, Sehrish Firyal, Yiqiang Zhao, et al.. The transmission of human mitochondrial DNA in four‐generation pedigrees. Human Mutation, 2022, 43, pp.1259-1267. ⟨10.1002/humu.24390⟩. ⟨hal-04604735⟩
0 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Mastodon Facebook X LinkedIn More