An Organismal CNV Mutator Phenotype Restricted to Early Human Development.
Cell
; 168(5): 830-842.e7, 2017 02 23.
Article
em En
| MEDLINE
| ID: mdl-28235197
ABSTRACT
De novo copy number variants (dnCNVs) arising at multiple loci in a personal genome have usually been considered to reflect cancer somatic genomic instabilities. We describe a multiple dnCNV (MdnCNV) phenomenon in which individuals with genomic disorders carry five to ten constitutional dnCNVs. These CNVs originate from independent formation incidences, are predominantly tandem duplications or complex gains, exhibit breakpoint junction features reminiscent of replicative repair, and show increased de novo point mutations flanking the rearrangement junctions. The active CNV mutation shower appears to be restricted to a transient perizygotic period. We propose that a defect in the CNV formation process is responsible for the "CNV-mutator state," and this state is dampened after early embryogenesis. The constitutional MdnCNV phenomenon resembles chromosomal instability in various cancers. Investigations of this phenomenon may provide unique access to understanding genomic disorders, structural variant mutagenesis, human evolution, and cancer biology.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Aberrações Cromossômicas
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Instabilidade Genômica
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Variações do Número de Cópias de DNA
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Doenças Genéticas Inatas
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Mutação
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Cell
Ano de publicação:
2017
Tipo de documento:
Article