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.
Typical enteropathogenic Escherichia coli (EPEC) strains produce bundle-forming pili (BFP), type IVB fimbriae that have been implicated in EPEC virulence, antigenicity, autoaggregation, and localized adherence to epithelial cells (LA). BFP are polymers of bundlin, a pilin protein that is encoded by the bfpA gene found on a large EPEC plasmid. Striking sequence variation has previously been observed among type IV pilin genes of other gram-negative bacterial pathogens (e.g., Pseudomonas and Neisseria spp.). In contrast, the established sequences of bfpA genes from two distantly related prototype EPEC strains vary by only a single base pair. To determine whether bundlin sequences vary more extensively, we used PCR to amplify the bfpA genes from 19 EPEC strains chosen for their various serotypes and sites and years of isolation. Eight different bfpA alleles were identified by sequencing of the PCR products. These alleles can be classified into two major groups. The ␣ group contains three alleles derived from strains carrying O55, O86, O111, O119, O127, or O128 somatic antigens. The  group contains five alleles derived from strains carrying O55, O110, O128ab, O142, or nontypeable antigens. Sequence comparisons show that bundlin has highly conserved and variable regions, with most of the variation occurring in the C-terminal two-thirds of the protein. The results of multilocus enzyme electrophoresis support the hypothesis that bfpA sequences have spread horizontally across distantly related clonal lineages. Strains with divergent bundlin sequences express bundlin protein, produce BFP, and carry out autoaggregation and LA. However, four strains lack most or all of these phenotypes despite having an intact bfpA gene. These results have important implications for our understanding of bundlin structure, transmission of the bfp gene cluster among EPEC strains, and the role of bundlin variation in the evasion of host immune system responses.Enteropathogenic Escherichia coli (EPEC) is one of several pathovars of E. coli capable of causing diarrhea (45). While human EPEC infections, which are manifest primarily in infants, were once commonplace in industrialized nations (56), they are now identified primarily in developing countries (10). EPEC strains possess distinct virulence factors not found in most E. coli strains (45). Typical EPEC strains produce bundleforming pili (BFP), long, flexible, rope-like structures composed of intertwining fibers (19). Based on protein sequence analysis and morphology, BFP belong to the type IV group of fimbriae or pili found on a variety of gram-negative bacteria, many of which are human, animal, or plant pathogens (67, 70, 77). BFP have recently been shown to elicit an antibody response in natural infections (37, 38, 53) and a modest response in experimentally infected adults (13). BFP are required for two phenotypes of EPEC that can be studied in vitro and probably play a role in colonization in vivo. The first is autoaggregation, which is the ability of EPEC to reversibly form multicellu...
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.
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.
A utistic spectrum disorders (MIM 209850), which include autism, Asperger syndrome, and pervasive developmental disorder (PDD) not otherwise specified, are characterised by impairment in communications and social interactions and the presence of stereotyped behaviours. The aetiology of autistic disorder is unknown, but family and twin studies have shown a high monozygotic to dizygotic twin risk ratio and a sib relative risk between 50 and 100, suggesting that inheritance of autism is complex, but the predisposition to develop it is largely genetically determined.
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