Traduction partielle: G.M.
PLoS One. 2013 Oct 17;8(10):e77906. doi: 10.1371/journal.pone.0077906.
Définir la contribution de CNTNAP2 à la susceptibilité à l'autisme
Source
Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetics Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.Abstract
Plusieurs sources de preuves génétiques suggèrent un rôle pour CNTNAP2 dans l'autisme.
Pour évaluer son impact sur la population , nous avons étudié 2148 polymorphismes nucléotides simples communs (SNP) en utilisant le test de déséquilibre de transmission (TDT ) sur l'ensemble de ~ 3,3 Mb CNTNAP2 du locus ( 408 trios )chez 186 familles multiplex et 323 familles simplex avec des troubles de spectre autistique ( TSA ) .
This analysis yielded two SNPs with nominal statistical significance (rs17170073, p = 2.0 x 10(-4); rs2215798, p = 1.6 x 10(-4)) that did not survive multiple testing. In a combined analysis of all families, two highly correlated (r (2) = 0.99) SNPs in intron 14 showed significant association with autism (rs2710093, p = 9.0 x 10(-6); rs2253031, p = 2.5 x 10(-5)). To validate these findings and associations at SNPs from previous autism studies (rs7794745, rs2710102 and rs17236239) we genotyped 2051 additional families (572 multiplex and 1479 simplex). None of these variants were significantly associated with ASD after corrections for multiple testing. The analysis of Mendelian errors within each family did not indicate any segregating deletions. Nevertheless, a study of CNTNAP2 gene expression in brains of autistic patients and of normal controls, demonstrated altered expression in a subset of patients (p = 1.9 x10(-5)).
Pour évaluer son impact sur la population , nous avons étudié 2148 polymorphismes nucléotides simples communs (SNP) en utilisant le test de déséquilibre de transmission (TDT ) sur l'ensemble de ~ 3,3 Mb CNTNAP2 du locus ( 408 trios )chez 186 familles multiplex et 323 familles simplex avec des troubles de spectre autistique ( TSA ) .
This analysis yielded two SNPs with nominal statistical significance (rs17170073, p = 2.0 x 10(-4); rs2215798, p = 1.6 x 10(-4)) that did not survive multiple testing. In a combined analysis of all families, two highly correlated (r (2) = 0.99) SNPs in intron 14 showed significant association with autism (rs2710093, p = 9.0 x 10(-6); rs2253031, p = 2.5 x 10(-5)). To validate these findings and associations at SNPs from previous autism studies (rs7794745, rs2710102 and rs17236239) we genotyped 2051 additional families (572 multiplex and 1479 simplex). None of these variants were significantly associated with ASD after corrections for multiple testing. The analysis of Mendelian errors within each family did not indicate any segregating deletions. Nevertheless, a study of CNTNAP2 gene expression in brains of autistic patients and of normal controls, demonstrated altered expression in a subset of patients (p = 1.9 x10(-5)).
Par conséquent , cette étude suggère que, bien que la dérégulation de CNTNAP2 joue un rôle dans certains cas , sa contribution dans la population à la susceptibilité à l'autisme est limitée.
- PMID: 24147096
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