Replicative mechanisms of CNV formation preferentially occur as intrachromosomal events: evidence from Potocki-Lupski duplication syndrome.
Hum Mol Genet
; 22(4): 749-56, 2013 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-23161748
ABSTRACT
Copy number variations (CNVs) in the human genome contribute significantly to disease. De novo CNV mutations arise via genomic rearrangements, which can occur in 'trans', i.e. via interchromosomal events, or in 'cis', i.e. via intrachromosomal events. However, what molecular mechanisms occur between chromosomes versus between or within chromatids has not been systematically investigated. We hypothesized that distinct CNV mutational mechanisms, based on their intrinsic properties, may occur in a biased intrachromosomal versus interchromosomal manner. Here, we studied 62 genomic duplications observed in association with sporadic Potocki-Lupski syndrome (PTLS), in which multiple mutational mechanisms appear to be operative. Intriguingly, more interchromosomal than intrachromosomal events were identified in recurrent PTLS duplications mediated by non-allelic homologous recombination, whereas the reciprocal distribution was found for replicative mechanisms and non-homologous end-joining, likely reflecting the differences in spacial proximity of homologous chromosomes during different mutational processes.
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Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 17
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Replicação do DNA
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Variações do Número de Cópias de DNA
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Síndrome de Smith-Magenis
Limite:
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article