Mosaic chromosomal alterations in blood across ancestries using whole-genome sequencing.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
04
11
2022
accepted:
27
09
2023
medline:
10
11
2023
pubmed:
31
10
2023
entrez:
31
10
2023
Statut:
ppublish
Résumé
Megabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program. We observed higher sensitivity with whole-genome sequencing data, compared with array-based data, in uncovering mCAs at low mutant cell fractions and found that individuals of European ancestry have the highest rates of autosomal mCAs and the lowest rates of chromosome X mCAs, compared with individuals of African or Hispanic ancestry. Although further studies in diverse populations will be needed to replicate our findings, we report three loci associated with loss of chromosome X, associations between autosomal mCAs and rare variants in DCPS, ADM17, PPP1R16B and TET2 and ancestry-specific variants in ATM and MPL with mCAs in cis.
Identifiants
pubmed: 37904051
doi: 10.1038/s41588-023-01553-1
pii: 10.1038/s41588-023-01553-1
pmc: PMC10632132
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1912-1919Informations de copyright
© 2023. The Author(s).
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