RESUMO
Reading disabilities (RD) have been linked and associated with markers on chromosome 6p with results from multiple independent samples pointing to KIAA0319 as a risk gene and specifically, the 5' region of this gene. Here we focus genetic studies on a 2.3 kb region spanning the predicted promoter, the first untranslated exon, and part of the first intron, a region we identified as a region of open chromatin. Using DNA from probands with RD, we screened for genetic variants and tested select variants for association. We identified 17 DNA variants in this sample of probands, 16 of which were previously reported in public databases and one previously identified in a screen of this region. Based on the allele frequencies in the probands compared to public databases, and on possible functional consequences of the variation, we selected seven variants to test for association in a sample of families with RD, in addition to four variants which had been tested previously. We also tested two markers 5' of this region that were previously reported as associated. The strongest evidence for association was observed with alleles of the microsatellite marker located in the first untranslated exon and haplotypes of that marker. These results support previous studies indicating the 5' region of the KIAA0319 gene as the location of risk alleles contributing to RD.
Assuntos
Regiões 5' não Traduzidas/genética , Alelos , Dislexia/genética , Predisposição Genética para Doença/genética , Variação Genética/genética , Proteínas do Tecido Nervoso/genética , Adolescente , Criança , Cromossomos Humanos Par 6/genética , Feminino , Frequência do Gene/genética , Estudos de Associação Genética , Genótipo , Haplótipos/genética , Humanos , Masculino , Repetições de Microssatélites , Ontário , Polimorfismo Genético/genéticaRESUMO
To examine the unity and diversity of inattention and hyperactivity/impulsivity symptom domains of Attention-Deficit/Hyperactivity Disorder (ADHD) in a clinical sample of adolescents with ADHD. Parents and adolescents were administered a semi-structured diagnostic interview, the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL), to assess adolescent ADHD. Data from 201 parent interviews and 189 adolescent interviews were examined. Four potential factor structures for the 18 ADHD symptoms were tested using confirmatory factor analysis: two models with correlated factors and two bifactor models. A bifactor model with two specific factors best accounted for adolescent symptoms, according to both parent and adolescents' reports. Replication of these findings from behavioral rating scales completed for this sample by parents and teachers indicates that the findings are not method- or informant-specific. The results suggest that there is an important unitary component to ADHD symptoms and separable dimensional traits of Inattention and Hyperactivity/Impulsivity.