Recurrent inversion polymorphisms in humans associate with genetic instability and genomic disorders.
L1 mobile element
genomic disorder
genomic instability
genomic structural variation
human genetic variation
inversion
pathogenic CNV
recurrent mutation
retrotransposon
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
26 05 2022
26 05 2022
Historique:
received:
11
11
2021
revised:
14
02
2022
accepted:
08
04
2022
pubmed:
8
5
2022
medline:
1
6
2022
entrez:
7
5
2022
Statut:
ppublish
Résumé
Unlike copy number variants (CNVs), inversions remain an underexplored genetic variation class. By integrating multiple genomic technologies, we discover 729 inversions in 41 human genomes. Approximately 85% of inversions <2 kbp form by twin-priming during L1 retrotransposition; 80% of the larger inversions are balanced and affect twice as many nucleotides as CNVs. Balanced inversions show an excess of common variants, and 72% are flanked by segmental duplications (SDs) or retrotransposons. Since flanking repeats promote non-allelic homologous recombination, we developed complementary approaches to identify recurrent inversion formation. We describe 40 recurrent inversions encompassing 0.6% of the genome, showing inversion rates up to 2.7 × 10
Identifiants
pubmed: 35525246
pii: S0092-8674(22)00464-0
doi: 10.1016/j.cell.2022.04.017
pmc: PMC9563103
mid: NIHMS1803457
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
1986-2005.e26Subventions
Organisme : NHGRI NIH HHS
ID : K99 HG011041
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG010961
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM138212
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG010973
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA034196
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG008901
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG010169
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG010963
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA261934
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG010971
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG007497
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG002385
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM133600
Pays : United States
Organisme : NHGRI NIH HHS
ID : U41 HG010972
Pays : United States
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests E.E.E. is a scientific advisory board (SAB) member of Variant Bio. C.L. is an SAB member of Nabsys. The following authors have previously disclosed a patent application (no. EP19169090) relevant to Strand-seq: A.D.S., J.O.K., T.M., and D.P.; the other authors declare no competing interests.
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