RESUMO
Autism is a neurodevelopmental syndrome defined by deficits in social reciprocity and communication and by unusual repetitive behaviors. Although there is an underlying genetic predisposition, the etiology of autism is currently unknown. A recent increase in prevalence suggests that genetically determined vulnerability to environmental exposure might contribute to the causation of autism. We performed family-based association studies of polymorphisms in metal-regulatory transcription factor 1(MTF1), a multispecific organic anion transporter (ABCC1), proton-coupled divalent metal ion transporters (SLC11A3 and SLC11A2), paraoxonase 1 (PON1), and glutathione S-transferase (GSTP1) genes in 196 autistic disorder families. There was deviation from the expected pattern of transmission for polymorphisms in MTF1 (Single nucleotide polymorphism database reference identification number, dbSNP rs3790625, P = .02) and divalent metal ion transporter SLC11A3 (dbSNP rs2304704, P = .07) genes. Although these results might represent chance finding, further investigations of genetic variations of metal metabolism in autism are warranted.
Assuntos
Transtorno Autístico/genética , Transtorno Autístico/fisiopatologia , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Xenobióticos/metabolismo , Xenobióticos/intoxicação , Criança , Proteínas de Ligação a DNA , Genótipo , Humanos , Desequilíbrio de Ligação , Fatores de Risco , Fator MTF-1 de TranscriçãoRESUMO
Genome scans indicate a linkage of autism to the chromosome 7q21-q36 region. Recent studies suggest that the Reelin gene may be one of the loci contributing to the positive linkage between chromosome 7q and autism. However, these studies were relatively small scale, using a few markers in the gene. We investigated 34 single nucleotide polymorphisms (SNPs) in the Reelin gene with an average spacing between the SNPs of 15 kb for evidence of association with autism. There were significant differences in the transmission of the alleles of exon 22 and intron 59 SNP to autistic subjects. Our findings support a role for the Reelin gene in the susceptibility to autism.
Assuntos
Transtorno Autístico/genética , Moléculas de Adesão Celular Neuronais/genética , Cromossomos Humanos Par 7/genética , Proteínas da Matriz Extracelular/genética , Ligação Genética , Predisposição Genética para Doença , Proteínas do Tecido Nervoso/genética , Polimorfismo de Nucleotídeo Único/genética , Serina Endopeptidases/genética , Alelos , Estudos de Casos e Controles , Éxons/genética , Feminino , Humanos , Íntrons/genética , Masculino , Proteína ReelinaRESUMO
Several independent genome scans have revealed excess allele sharing in an overlapping 40 cM region of 7q21-34 in autism. DLX6 and Piccolo (PCLO) at 7q21-q22 are two positional and functional candidate genes in autism. We have investigated a single nucleotide polymorphism (SNP) in exon 4 of the PCLO gene and a SNP in intron 1 of the DLX6 gene for linkage and association in autistic disorder using both qualitative and quantitative analyses. One hundred ninety-six multiplex autistic disorder families were tested using transmission disequilibrium and two-point affected sib pair linkage analysis. We found no evidence of association or linkage with the two intragenic markers. In addition, there was also no linkage or association between language and stereotypic behavior quantitative traits in autism and the SNPs. In conclusion, our studies suggest that these two SNPs in DLX6 and PCLO genes are not in linkage disequilibrium with autism.
Assuntos
Transtorno Autístico/genética , Cromossomos Humanos Par 7 , Proteínas do Citoesqueleto/genética , Proteínas de Homeodomínio/genética , Neuropeptídeos/genética , Polimorfismo de Nucleotídeo Único , Interpretação Estatística de Dados , Saúde da Família , Predisposição Genética para Doença , Humanos , Padrões de Herança , Transtornos da Linguagem , Desequilíbrio de Ligação , Comportamento EstereotipadoRESUMO
Although elevation of blood and platelet serotonin has been documented in autism, genetic analyses of serotonin transporter gene have given conflicting results. Tryptophan 2,3 dioxygenase (TDO2) is the rate-limiting enzyme in the catabolism of tryptophan, the precursor of serotonin. A mutation that results in decreased activity of the TDO2 can decrease catabolism of tryptophan and increase the level of whole body serotonin. As such it is a potential candidate gene for autism. We have investigated five single nucleotide polymorphisms in the TDO2 gene for association with autistic disorder. One hundred and ninety six multiplex autistic disorder families were tested using transmission disequilibrium test. There was a significant difference in the transmission of a promoter variant to autistic subjects (P = 0.0006). Haplotype analysis also demonstrated significant difference in the transmission of TDO2 haplotypes to autistic subjects (P = 0.0027). Our results suggest the presence of a susceptibility mutation in the TDO2 or a nearby gene, but may also represent a chance finding.
Assuntos
Transtorno Autístico/genética , Predisposição Genética para Doença , Haplótipos/genética , Desequilíbrio de Ligação/genética , Triptofano Oxigenase/genética , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Serotonina/metabolismoRESUMO
We describe two serogroup O157 Escherichia coli strains from Brazilian infants with diarrhea. A variety of assays indicate that these strains belong to the enteropathogenic, not the enterohemorrhagic, pathotype. These strains possess a novel bfpA allele encoding the type IV pilin characteristic of typical enteropathogenic E. coli strains. Our results emphasize the pitfalls of classifying pathogenic E. coli by serogroup.