Mapping recurrent mosaic copy number variation in human neurons.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 May 2024
17 May 2024
Historique:
received:
03
03
2023
accepted:
29
04
2024
medline:
18
5
2024
pubmed:
18
5
2024
entrez:
17
5
2024
Statut:
epublish
Résumé
When somatic cells acquire complex karyotypes, they often are removed by the immune system. Mutant somatic cells that evade immune surveillance can lead to cancer. Neurons with complex karyotypes arise during neurotypical brain development, but neurons are almost never the origin of brain cancers. Instead, somatic mutations in neurons can bring about neurodevelopmental disorders, and contribute to the polygenic landscape of neuropsychiatric and neurodegenerative disease. A subset of human neurons harbors idiosyncratic copy number variants (CNVs, "CNV neurons"), but previous analyses of CNV neurons are limited by relatively small sample sizes. Here, we develop an allele-based validation approach, SCOVAL, to corroborate or reject read-depth based CNV calls in single human neurons. We apply this approach to 2,125 frontal cortical neurons from a neurotypical human brain. SCOVAL identifies 226 CNV neurons, which include a subclass of 65 CNV neurons with highly aberrant karyotypes containing whole or substantial losses on multiple chromosomes. Moreover, we find that CNV location appears to be nonrandom. Recurrent regions of neuronal genome rearrangement contain fewer, but longer, genes.
Identifiants
pubmed: 38760338
doi: 10.1038/s41467-024-48392-0
pii: 10.1038/s41467-024-48392-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4220Subventions
Organisme : NIMH NIH HHS
ID : U01 MH106882
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH106893
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH106892
Pays : United States
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : U01 MH106892 supplement
Organisme : NIMH NIH HHS
ID : U01 MH106892
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH106892
Pays : United States
Investigateurs
Joseph G Gleeson
(JG)
Martin W Breuss
(MW)
Xiaoxu Yang
(X)
Danny Antaki
(D)
Changuk Chung
(C)
Dan Averbuj
(D)
Laurel L Ball
(LL)
Subhojit Roy
(S)
Daniel Weinberger
(D)
Andrew Jaffe
(A)
Apua Paquola
(A)
Jennifer Erwin
(J)
Richard Straub
(R)
Rujuta Narurkar
(R)
Gary Mathern
(G)
Christopher A Walsh
(CA)
Alice Lee
(A)
August Yue Huang
(AY)
Alissa D'Gama
(A)
Caroline Dias
(C)
Eduardo Maury
(E)
Javier Ganz
(J)
Michael Lodato
(M)
Michael Miller
(M)
Pengpeng Li
(P)
Rachel Rodin
(R)
Rebeca Borges-Monroy
(R)
Robert Hill
(R)
Sara Bizzotto
(S)
Sattar Khoshkhoo
(S)
Sonia Kim
(S)
Zinan Zhou
(Z)
Peter J Park
(PJ)
Alison Barton
(A)
Alon Galor
(A)
Chong Chu
(C)
Craig Bohrson
(C)
Doga Gulhan
(D)
Elaine Lim
(E)
Euncheon Lim
(E)
Giorgio Melloni
(G)
Isidro Cortes
(I)
Jake Lee
(J)
Joe Luquette
(J)
Lixing Yang
(L)
Maxwell Sherman
(M)
Michael Coulter
(M)
Minseok Kwon
(M)
Semin Lee
(S)
Soo Lee
(S)
Vinary Viswanadham
(V)
Yanmei Dou
(Y)
Andrew J Chess
(AJ)
Attila Jones
(A)
Chaggai Rosenbluh
(C)
Schahram Akbarian
(S)
Ben Langmead
(B)
Jeremy Thorpe
(J)
Sean Cho
(S)
Alexej Abyzov
(A)
Taejeong Bae
(T)
Yeongjun Jang
(Y)
Yifan Wang
(Y)
Cindy Molitor
(C)
Mette Peters
(M)
Fred H Gage
(FH)
Meiyan Wang
(M)
Patrick Reed
(P)
Sara Linker
(S)
Alexander Urban
(A)
Bo Zhou
(B)
Reenal Pattni
(R)
Xiaowei Zhu
(X)
Aitor Serres Amero
(AS)
David Juan
(D)
Inna Povolotskaya
(I)
Irene Lobon
(I)
Manuel Solis Moruno
(MS)
Raquel Garcia Perez
(RG)
Tomas Marques-Bonet
(T)
Eduardo Soriano
(E)
John V Moran
(JV)
Diane A Flasch
(DA)
Trenton J Frisbie
(TJ)
Huira C Kopera
(HC)
John B Moldovan
(JB)
Kenneth Y Kwan
(KY)
Ryan E Mills
(RE)
Weichen Zhou
(W)
Xuefang Zhao
(X)
Aakrosh Ratan
(A)
Flora M Vaccarino
(FM)
Adriana Cherskov
(A)
Alexandre Jourdon
(A)
Liana Fasching
(L)
Nenad Sestan
(N)
Sirisha Pochareddy
(S)
Soraya Scuder
(S)
Informations de copyright
© 2024. The Author(s).
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