Contribution of copy-number variation to Down syndrome-associated atrioventricular septal defects.
Genet Med
; 17(7): 554-60, 2015 Jul.
Article
em En
| MEDLINE
| ID: mdl-25341113
ABSTRACT
PURPOSE:
The goal of this study was to identify the contribution of large copy-number variants to Down syndrome-associated atrioventricular septal defects, the risk for which in the trisomic population is 2,000-fold more as compared with that of the general disomic population.METHODS:
Genome-wide copy-number variant analysis was performed on 452 individuals with Down syndrome (210 cases with complete atrioventricular septal defects; 242 controls with structurally normal hearts) using Affymetrix SNP 6.0 arrays, making this the largest heart study conducted to date on a trisomic background.RESULTS:
Large, common copy-number variants with substantial effect sizes (OR > 2.0) do not account for the increased risk observed in Down syndrome-associated atrioventricular septal defects. By contrast, cases had a greater burden of large, rare deletions (P < 0.01) and intersected more genes (P < 0.007) as compared with controls. We also observed a suggestive enrichment of deletions intersecting ciliome genes in cases as compared with controls.CONCLUSION:
Our data provide strong evidence that large, rare deletions increase the risk of Down syndrome-associated atrioventricular septal defects, whereas large, common copy-number variants do not appear to increase the risk of Down syndrome-associated atrioventricular septal defects. The genetic architecture of atrioventricular septal defects is complex and multifactorial in nature.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Síndrome de Down
/
Variações do Número de Cópias de DNA
/
Defeitos dos Septos Cardíacos
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article