CNV Characterization, Inheritance and Phenotypic Correlations in Families With ...

• Autor(es): C. Conceição, Inês ; Correia, Catarina ; Oliveira, Bárbara ; M. Rama, Maria ; Café, Cátia ; Almeida, Joana ; Mouga, Susana ; Duque, Frederico ; Oliveira, Guiomar ; M. Vicente, Astrid
• Data: 2013
• Identificador Persistente: http://hdl.handle.net/10400.18/1639
• Origem: Repositório Científico do Instituto Nacional de Saúde
• Assunto(s): Perturbações do Desenvolvimento Infantil e Saúde Mental; Autism; Autism Spectrum Disorders; ASD
• Tipo de Documento: Documento de conferência
• Idioma: Inglês

Descrição

Autism Spectrum Disorders (ASD) have a strong genetic component, with an estimated heritability of over 90%1. Recent studies carried out by the Autism Genome Project (AGP) consortium suggest that rare Copy Number Variants (CNVs), characterized by submicroscopic chromosomal deletions and duplications, are more frequent in ASD compared to controls, and may play an important role in susceptibility to this disorder2. However, to adequately assess pathogenicity, a detailed characterization of patients CNVs and phenotype is required. The goal of this study was to establish the clinical and etiological relevance for ASD of potentially pathogenic CNVs identified in a Portuguese population sample by whole genome CNV analysis, through the detailed characterization of CNVs and correlation with clinical phenotypes. Analysis of the AGP genome-wide CNV results using 1M SNP microarray2 identified a total of 14218 CNVs in 342 Portuguese probands. We selected 291 CNVs, present in 191 individuals (19 females and 172 males), using the following criteria: 1) CNVs that contained implicated/candidate genes for ASD; 2) CNVs in genomic regions known to be implicated/candidate for ASD; 3) CNVs in regions associated with syndromes with ASD symptoms; and 4) high confidence CNVs that did not overlap more than 20% with controls in available databases. We explored recurrence rates, genic content, regulatory elements, inheritance patterns and phenotypic correlations.