The rate and nature of mitochondrial DNA mutations in human pedigrees.

Autor:	Árnadóttir ER; deCODE Genetics/Amgen Inc., Reykjavik, Iceland., Moore KHS; deCODE Genetics/Amgen Inc., Reykjavik, Iceland., Guðmundsdóttir VB; deCODE Genetics/Amgen Inc., Reykjavik, Iceland; Department of Anthropology, University of Iceland, Reykjavik, Iceland., Ebenesersdóttir SS; deCODE Genetics/Amgen Inc., Reykjavik, Iceland., Guity K; deCODE Genetics/Amgen Inc., Reykjavik, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland., Jónsson H; deCODE Genetics/Amgen Inc., Reykjavik, Iceland., Stefánsson K; deCODE Genetics/Amgen Inc., Reykjavik, Iceland; Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. Electronic address: kstefans@decode.is., Helgason A; deCODE Genetics/Amgen Inc., Reykjavik, Iceland; Department of Anthropology, University of Iceland, Reykjavik, Iceland. Electronic address: agnar.helgason@decode.is.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2024 Jul 25; Vol. 187 (15), pp. 3904-3918.e8. Date of Electronic Publication: 2024 Jun 07.
DOI:	10.1016/j.cell.2024.05.022
Abstrakt:	We examined the rate and nature of mitochondrial DNA (mtDNA) mutations in humans using sequence data from 64,806 contemporary Icelanders from 2,548 matrilines. Based on 116,663 mother-child transmissions, 8,199 mutations were detected, providing robust rate estimates by nucleotide type, functional impact, position, and different alleles at the same position. We thoroughly document the true extent of hypermutability in mtDNA, mainly affecting the control region but also some coding-region variants. The results reveal the impact of negative selection on viable deleterious mutations, including rapidly mutating disease-associated 3243A>G and 1555A>G and pre-natal selection that most likely occurs during the development of oocytes. Finally, we show that the fate of new mutations is determined by a drastic germline bottleneck, amounting to an average of 3 mtDNA units effectively transmitted from mother to child. Competing Interests: Declaration of interests The authors of this study are employed by deCODE genetics, a subsidiary of Amgen Inc. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu