Long-read sequencing reveals the complex structure of extra dic(21;21) chromosome and its biological effects.
Journal
Human genetics
ISSN: 1432-1203
Titre abrégé: Hum Genet
Pays: Germany
ID NLM: 7613873
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
12
04
2023
accepted:
27
06
2023
medline:
25
8
2023
pubmed:
11
7
2023
entrez:
11
7
2023
Statut:
ppublish
Résumé
Complex congenital chromosome abnormalities are rare but often cause severe symptoms. However, the structures and biological impacts of such abnormalities have seldomly been analyzed at the molecular level. Previously, we reported a Japanese female patient with severe developmental defects. The patient had an extra dicentric chromosome 21 (chr21) consisting of two partial chr21 copies fused together within their long arms along with two centromeres and many copy number changes. In this study, we performed whole-genome, transcriptional, and DNA methylation analyses, coupled with novel bioinformatic approaches, to reveal the complex structure of the extra chromosome and its transcriptional and epigenetic changes. Long-read sequencing accurately identified the structures of junctions related to the copy number changes in extra chr21 and suggested the mechanism of the structural changes. Our transcriptome analysis showed the overexpression of genes in extra chr21. Additionally, an allele-specific DNA methylation analysis of the long-read sequencing data suggested that the centromeric region of extra chr21 was hypermethylated, a property associated with the inactivation of one centromere in the extra chromosome. Our comprehensive analysis provides insights into the molecular mechanism underlying the generation of the extra chromosome and its pathogenic roles.
Identifiants
pubmed: 37432452
doi: 10.1007/s00439-023-02583-9
pii: 10.1007/s00439-023-02583-9
pmc: PMC10449678
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1375-1384Subventions
Organisme : AMED
ID : 20km0405207h9905
Informations de copyright
© 2023. The Author(s).
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