Circulating DNA reveals a specific and higher fragmentation of the Y chromosome.
Journal
Human genetics
ISSN: 1432-1203
Titre abrégé: Hum Genet
Pays: Germany
ID NLM: 7613873
Informations de publication
Date de publication:
Nov 2023
Nov 2023
Historique:
received:
21
06
2023
accepted:
11
09
2023
medline:
30
10
2023
pubmed:
25
9
2023
entrez:
24
9
2023
Statut:
ppublish
Résumé
Chromosome stability is a key point in genome evolution, particularly that of the Y chromosome. The Y chromosome loss in blood and tumor cells is well established. Through processes that are common to other chromosomes too, the Y chromosome undergoes degradation and fragmentation in the blood stream before elimination. This process gives rise to circulating DNA (cirDNA) fragments, whose examination may provide potential insight into the role of DNA fragmentation in blood for the Y chromosome elimination. In this study, we employed shallow whole genome sequencing (sWGS) to comprehensively assess the total cirDNA and the individual chromosome fragment size profiles in the plasma of healthy male individuals. Here, we show that (i) the fragment size profiles of total circulating DNA (cirDNA) and DNA fragments originating from autosomes and the X chromosome in blood plasma are homogeneous, and have a remarkably low variability (mean CV = 7%) among healthy individuals, (ii) the Y chromosome has a distinct fragment size profile with the accumulation of the fragment < 145 bp and depletion of the dinucleosome-associated fragments (290-390 bp), and its fragment fraction in blood decreases with age. These results indicate a higher fragmentation of the Y chromosome compared to other chromosomes and this in turn might be due to its increased susceptibility to degradation. Our findings pave the way for an elucidation of the impact of chromosomal origin on DNA degradation and the Y chromosome biology.
Identifiants
pubmed: 37743368
doi: 10.1007/s00439-023-02600-x
pii: 10.1007/s00439-023-02600-x
doi:
Substances chimiques
DNA
9007-49-2
Cell-Free Nucleic Acids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1603-1609Subventions
Organisme : SIRIC Montpellier Cancer Grant
ID : INCa_Inserm_DGOS_12553
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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