Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic studies indicate that chromosome 7q is likely to contain an autism susceptibility locus (AUTS1). We have followed a positional candidate gene approach to identify relevant gene(s) and report here the analysis of reelin (RELN), a gene located under our peak of linkage. Screening RELN for DNA changes identified novel missense variants absent in a large control group; however, the low frequency of these mutations does not explain the relatively strong linkage results on 7q. Furthermore, analysis of a previously reported triplet repeat polymorphism and intragenic single nucleotide polymorphisms, using the transmission disequilibrium test, provided no evidence for association with autism in IMGSAC and German singleton families. The analysis of RELN suggests that it probably does not play a major role in autism aetiology, although further analysis of several missense mutations is warranted in additional affected individuals.
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PMID:Analysis of reelin as a candidate gene for autism. 1451 39

The results from several genome scans indicate that chromosome 2q21-q33 is likely to contain an autism susceptibility locus. We studied the potential contribution of nine positional and functional candidate genes: TBR-1; GAD1; DLX1; DLX2; cAMP-GEFII; CHN1; ATF2; HOXD1 and NEUROD1. Screening these genes for DNA variants and association analysis using intragenic single nucleotide polymorphisms did not provide evidence for a major role in the aetiology of autism. Four rare nonsynonymous variants were identified, however, in the cAMP-GEFII gene. These variants were present in five families, where they segregate with the autistic phenotype, and were not observed in control individuals. The significance of these variants is unclear, as their low frequency in IMGSAC families does not account for the relatively strong linkage signal at the 2q locus. Further studies are needed to clarify the contribution of cAMP-GEFII gene variants to autism susceptibility.
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PMID:Screening of nine candidate genes for autism on chromosome 2q reveals rare nonsynonymous variants in the cAMP-GEFII gene. 1459 29

Common genetic disorders are believed to arise from the combined effects of multiple inherited genetic variants acting in concert with environmental factors, such that any given DNA sequence variant may have only a marginal effect on disease outcome. As a consequence, the correlation between disease status and any given DNA marker allele in a genomewide linkage study tends to be relatively weak and the implicated regions typically encompass hundreds of positional candidate genes. Therefore, new strategies are needed to parse relatively large sets of 'positional' candidate genes in search of actual disease-related gene variants. Here we use biological databases to identify 383 positional candidate genes predicted by genomewide genetic linkage analysis of a large set of families, each with two or more members diagnosed with autism, or autism spectrum disorder (ASD). Next, we seek to identify a subset of biologically meaningful, high priority candidates. The strategy is to select autism candidate genes based on prior genetic evidence from the allelic association literature to query the known transcripts within the 1-LOD (logarithm of the odds) support interval for each region. We use recently developed bioinformatic programs that automatically search the biological literature to predict pathways of interacting genes (PATHWAYASSIST and GENEWAYS). To identify gene regulatory networks, we search for coexpression between candidate genes and positional candidates. The studies are intended both to inform studies of autism, and to illustrate and explore the increasing potential of bioinformatic approaches as a compliment to linkage analysis.
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PMID:Bioinformatic analysis of autism positional candidate genes using biological databases and computational gene network prediction. 1460 95

Two recent studies have reported conflicting findings of association of a variant in the HOXA1 gene and autism. To try to resolve the conflict in findings, we conducted an association study in 78 Irish families of the reported DNA variants. We did not find statistically significant association between the variants and autism. Similarly there was no evidence of preferential transmission of variants from parent of either sex to affected offspring. We also report negative findings for HOXB1 variants. We conclude that the HOXA1/B1 are unlikely to be the susceptibility genes for autism in our sample.
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PMID:No association between allelic variants of HOXA1/HOXB1 and autism. 1468 17

The measles-mumps-rubella (MMR) vaccine has been very effective in the elimination of disease and has high biosafety. However, it has been associated with several adverse effects and has recently caused controversy with regard to its possible association with inflammatory bowel disease and autism. This has been postulated to be a property of the measles component of the vaccine, and a "new variant" autism has recently been described and suggested to be associated with vaccine virus. Although one study has reported the presence of measles RNA in inflammatory bowel disease associated with autism, this has not been independently confirmed. This and most of the other demonstrated or perceived adverse effects of the MMR vaccine could theoretically be ascribed to its composition as a mixture of three live replicating viruses, one of which (measles) can induce immunosuppression, although this hypothesis is speculative. It may nonetheless be desirable to improve the biosafety of the MMR vaccine by the development of a nonreplicating vaccine that will stimulate efficient immunity and protection. DNA vaccines for measles, mumps, and rubella viruses have been constructed and tested in animal models but are poorly immunogenic. Several other prototype candidate vaccines are possible, including those based on the rubella virus component of the vaccine as a vector.
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PMID:Is an improved measles-mumps-rubella vaccine necessary or feasible? 1470 Feb 73

Traditional nonparametric "multipoint" statistical procedures have been developed for assigning allele-sharing values at a locus of interest to pairs of relatives for linkage studies. These procedures attempt to accommodate a lack of informativity, nongenotyped loci, missing data, and related issues concerning the genetic markers used in a linkage study. However, such procedures often cannot overcome these phenomena in compelling ways and, as a result, assign relevant relative pairs allele-sharing values that are "expected" for those pairs. The practice of assigning expected allele-sharing values to relative pairs in the face of a lack of explicit allele-transmission information can bias traditional nonparametric linkage test statistics toward the null hypothesis of no locus effect. This bias is due to the use of expected values, rather than to a lack of information about actual allele sharing at relevant marker loci. The bias will vary from study to study on the basis of the DNA markers, sample size, relative-pair types, and pedigree structures used, but it can be extremely pronounced and could contribute to a lack of consistent success in the application of traditional nonparametric linkage analyses to complex human traits and diseases. There are several potential ways to overcome this problem, but their foundations deserve greater research. We expose many of the issues concerning allele sharing with data from a large affected-sibling-pair study investigating the genetic basis of autism.
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PMID:Inherent bias toward the null hypothesis in conventional multipoint nonparametric linkage analysis. 1533 60

Mutation screening of the RAB3A gene in 47 individuals with autism provided no evidence that DNA variants in this gene are associated with autism. Since Rab3a constitutive knockout mice react to novel stimuli with hyperactivity, a further search for association of RAB3A DNA variants with other neurobehavioral disorders such as attention deficit/hyperactivity disorder appears justified.
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PMID:DNA variants in the human RAB3A gene are not associated with autism. 1500 21

Autism is a pervasive neurodevelopmental disorder characterized by deficits in language development and social interaction, as well as stereotypical, repetitive behaviors. The etiology of autism is largely unknown. Family and twin studies have provided compelling evidence for a strong genetic component in most idiopathic cases. Several recent candidate gene studies have suggested that alleles of WNT2 and the reelin gene (RELN), two genes involved in distinct aspects of neurodevelopment, confer greater susceptibility to autism. We screened WNT2 for DNA polymorphisms by sequencing all exons and adjacent intronic regions in 24 autistic patients, and identified not only the WNT2 variants reported previously (two common single-nucleotide polymorphisms (SNPs) in the 5' upstream region and the 3' untranslated region (UTR), respectively), but also two new SNPs in its 3' UTR. We genotyped all four WNT2 polymorphisms and a polymorphic trinucleotide repeat in the 5' UTR of RELN in 107 families with multiple autistic children, and evaluated evidence for association between these variants and autism by the transmission disequilibrium test (TDT). Our results revealed no deviation from the null hypothesis of no association. Our interpretation of these findings is that it is unlikely that DNA variations in RELN and WNT2 play a significant role in the genetic predisposition to autism.
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PMID:Lack of evidence for an association between WNT2 and RELN polymorphisms and autism. 1504 48

The highly evolutionarily conserved serotonin transporter (SERT) regulates the entire serotoninergic system and its receptors via modulation of extracellular fluid serotonin concentrations. Differences in SERT expression and function produced by three SERT genes and their variants show associations with multiple human disorders. Screens of DNA from patients with autism, ADHD, bipolar disorder, and Tourette's syndrome have detected signals in the chromosome 17q region where SERT is located. Parallel investigations of SERT knockout mice have uncovered multiple phenotypes that identify SERT as a candidate gene for additional human disorders ranging from irritable bowel syndrome to obesity. Replicated studies have demonstrated that the SERT 5'-flanking region polymorphism SS genotype is associated with poorer therapeutic responses and more frequent serious side effects during treatment with antidepressant SERT antagonists, namely, the serotonin reuptake inhibitors (SRIs).
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PMID:Serotonin transporter: gene, genetic disorders, and pharmacogenetics. 1508 84

Sex steroids exert potent effects on mood and mental state in humans. They may contribute to the risk of psychiatric disorders. To investigate this hypothesis, coding and splice junction sequences of the androgen receptor gene were scanned in genomic DNA samples to search for variants affecting protein structure and expression (VAPSEs). Ninety-six schizophrenics, along with pilot samples of patients with bipolar disorder, attention-deficit hyperactivity disorder, alcoholism and autism were analyzed with DOVAM-S, a robotically enhanced, optimized form of single-strand conformation polymorphism analysis. A total of 669 kb of genomic sequence was analyzed. Two VAPSEs were identified: R726L was found in one of 17 scanned alcoholics, and P516S, a novel VAPSE, was identified in one of three phobia patients. There were no length trends of the CAG triplets associated with schizophrenia. R726L and P516S occur at highly conserved amino acids. Further study is required to assess whether these VAPSEs contribute to the risk of alcoholism or phobia or other diseases.
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PMID:Mutation scanning of the androgen receptor gene in patients with psychiatric disorders reveals highly conserved variants in alcoholic and phobia patients. 1509 18


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