Developmental and temporal characteristics of clonal sperm mosaicism.
autism spectrum disorder
clonal mosaicism
congenital disorders
de novo mutation
embryogenesis
mutational signature
somatic
sperm
transmission risk
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
02 09 2021
02 09 2021
Historique:
received:
01
03
2021
revised:
12
05
2021
accepted:
14
07
2021
pubmed:
14
8
2021
medline:
5
1
2022
entrez:
13
8
2021
Statut:
ppublish
Résumé
Throughout development and aging, human cells accumulate mutations resulting in genomic mosaicism and genetic diversity at the cellular level. Mosaic mutations present in the gonads can affect both the individual and the offspring and subsequent generations. Here, we explore patterns and temporal stability of clonal mosaic mutations in male gonads by sequencing ejaculated sperm. Through 300× whole-genome sequencing of blood and sperm from healthy men, we find each ejaculate carries on average 33.3 ± 12.1 (mean ± SD) clonal mosaic variants, nearly all of which are detected in serial sampling, with the majority absent from sampled somal tissues. Their temporal stability and mutational signature suggest origins during embryonic development from a largely immutable stem cell niche. Clonal mosaicism likely contributes a transmissible, predicted pathogenic exonic variant for 1 in 15 men, representing a life-long threat of transmission for these individuals and a significant burden on human population health.
Identifiants
pubmed: 34388390
pii: S0092-8674(21)00883-7
doi: 10.1016/j.cell.2021.07.024
pmc: PMC8496133
mid: NIHMS1731652
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4772-4783.e15Subventions
Organisme : NCRR NIH HHS
ID : S10 RR029130
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH108898
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH124890
Pays : United States
Organisme : NINDS NIH HHS
ID : P30 NS047101
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001442
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIH HHS
ID : S10 OD026929
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG070462
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS083823
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests M.W.B., D.A., K.N.J., J.S., and J.G.G. are inventors on a patent (PCT/US2018/024878, WO2018183525A1) filed by University of California, San Diego that is titled “Methods for assessing risk of or diagnosing genetic defects by identifying de novo mutations or somatic mosaic variants in sperm or somatic tissues”.
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