Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathogenesis of schizophrenia might involve abnormal development of the human brain. Interleukin-1 beta is a cytokine implicated in the development of the central nervous system and therefore its gene is a candidate gene in schizophrenia. Polymorphisms within the coding sequence and the 3'UTR of the IL1 beta gene were searched for using PCR-SSCP. Two polymorphisms, 1B-175/1B-173 and 1B-1765/1B-1763 were found in addition to the previously published TaqI site. Furthermore, a mutant was found in codon 106 (exon 5) of the IL1 beta gene located next to the published polymorphism at the TaqI site and abolishing this site. This novel mutation encodes an Asp in place of an Asn and was only observed in one patient in our French population. Association studies were conducted with the polymorphisms 1B-175/1B-173 and TaqI. There was no allelic or genotypic association between either of the two polymorphisms and schizophrenia. In our population, there is no evidence that the IL1 beta gene is involved in schizophrenia.
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PMID:Detection of two new polymorphic sites in the human interleukin-1 beta gene: lack of association with schizophrenia in a French population. 932 21

Expansion mutations of trinucleotide repeats and other units of unstable DNA have been proposed to account for at least some of the genetic susceptibility to a number of neuropsychiatric disorders, including bipolar affective disorder, schizophrenia, autism, and panic disorder. To generate additional candidate genes for these and other disorders, cDNA libraries from human brain were probed at high stringency for clones containing CCG, CGC, GCC, CGG, GCG, and GGC repeats (referred to collectively as CCG repeats). Some 18 cDNAs containing previously unpublished or uncharacterized repeats were characterized for chromosomal locus, repeat length polymorphism, and similarity to genes of known function. The cDNAs were also compared with the 37 human genes with eight or more consecutive CCG triplets in GenBank. The repeats were mapped to a number of loci, including 1p34, 2p11.2, 2q30-32, 3p21, 3p22, 4q35, 6q22, 7qter, 13p13, 17q24, 18p11, 19p13.3, 20q12, 20q13.3, and 22q12. Length polymorphism was detected in 50% of the repeats. The newly cloned cDNAs include a complete transcript of human neurexin-1B, a portion of BCNG-1 (a newly described brain-specific ion channel), a previously unreported polymorphic repeat located in the 5' UTR region of the guanine nucleotide-binding protein (G-protein) beta2 subunit, and a human version of the mouse proline-rich protein 7. This list of cDNAs should expedite the search for expansion mutations associated with diseases of the central nervous system.
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PMID:CCG repeats in cDNAs from human brain. 992 1

We studied the relationship between schizophrenia and the DdeI polymorphism in the 5' untranslated region (5'UTR) of the dopamine D1 receptor (DRD1) gene. This polymorphism is an A (A1 allele) to G (A2 allele) transition in the 5' UTR of exon 2 at bp -48 (A-48G). One hundred forty-eight schizophrenics and 148 control subjects were investigated. No significant differences in genotypic counts and allele frequencies between schizophrenics and controls were found. Although a significant difference between the patients classified as disorganized type and the controls was discovered both in genotypic counts and allele frequencies, neither association proved significant when a Bonferroni correction was used. Moreover, there were no differences in scores of main symptoms of schizophrenia based on the Manchester Scale between patients with A1/A1 genotype and those with A1/A2 genotype. These findings suggest that this gene may not be involved in the pathogenesis of schizophrenia.
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PMID:Dopamine D1 receptor gene polymorphism and schizophrenia in Japan. 1020 27

Microtubule-associated protein-2 (MAP-2) expression is altered in response to a number of physiological insults such as Alzheimer's disease, schizophrenia, stroke and AIDS-dementia. Changes include alteration in MAP-2 transcription, translation, and state of phosphorylation. Multiple MAP-2 transcripts exist within the nervous system and, as noted for a number of genes expressed in the central nervous system, MAP-2 contains a region of trinucleotide repeats located in exon 1 of the 5' untranslated region (5' UTR). Since expansion of CAG repeats are found in several neurodegenerative disorders, we analysed the CAG repeats in MAP-2 for polymorphisms in 31 controls, 35 chronic schizophrenics, and 20 with other neuropsychiatric illnesses. Genomic DNA samples from 86 individuals were used as templates in PCR amplifications with primers within exon 1. Sequencing of the PCR products, or short tandem repeat polymorphism (STRP) analysis, demonstrated consistency in the size of the CAG repeats. This study demonstrates that the seven copies of the CAG repeat located in the 5' UTR of the MAP-2 gene are highly conserved in the general population, and that there is no evidence for expansion of the CAG repeat.
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PMID:Survey for CAG repeat polymorphisms in the human MAP-2 gene. 1033 52

Aromatic L-amino acid decarboxylase (AADC) is a relatively non specific enzyme involved in the biosynthesis of several classical neurotransmitters including dopamine and 5-hydroxytryptamine (5HT; serotonin). AADC does not catalyse the rate limiting step in either pathway, but is rate limiting in the synthesis of 2-phenylethylamine (2PE) which is a positive modulator of dopaminergic transmission and a candidate natural psychotogenic compound.1 We and others have proposed that polymorphism in AADC resulting in altered 2PE activity might contribute to the pathogenesis of psychosis. In order to test this hypothesis, we have used denaturing high performance liquid chromatography (DHPLC)3 to screen 3943 bases of the AADC gene and its promoter regions for variants that might affect protein structure or expression in 15 unrelated people with schizophrenia, and 15 unrelated people with bipolar disorder. Three polymorphisms were identified by DHPLC: a insertion/deletion polymorphism in the 5' UTR of the neuronal specific mRNA (g.-33-30delAGAG, bases 586-589 of GenBank M77828), a T>A variant in the non-neuronal exon 1 (g. -67T>A, GenBank M88070), and a G>A polymorphism within intron 8 (g. IVS8 +75G>A, GenBank M84598). Case-control analysis did not suggest that genetic polymorphism in the AADC gene is associated with liability for developing schizophrenia or bipolar disorder.
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PMID:Comparative sequencing and association studies of aromatic L-amino acid decarboxylase in schizophrenia and bipolar disorder. 1088 38

Glutamatergic dysregulation has been hypothesized to play a role in schizophrenia. The N-methyl-D-aspartate (NMDA) type of glutamate receptor especially is of interest because, in addition to binding sites for glutamate and glycine, a necessary co-agonist, this receptor also contains noncompetitive binding sites for the psychotomimetics phencyclidine (PCP), MK-801, and ketamine. PCP-induced psychosis has been a useful disease model in that both the positive as well as the negative symptomatologies seen in schizophrenia are observed. Recently, a mouse deficient in expression of the NR1 subunit gene (NMDAR1) of the heteromeric receptor has been developed and shown to display aberrant behaviors, with reduced social and sexual interactions as well as increased stereotypic motor activity. In an extensive examination of the NMDAR1 gene in our laboratory in approximately 100 chronic schizophrenic patients, 28 unique sequence changes were identified, including eight single nucleotide polymorphisms (SNPs) in the 5' untranslated region (5'UTR), six SNPs in coding regions (cSNPs), eleven intronic SNPs, two intronic deletions of 7 and 30 bp, and an intronic microinsertion/deletion. With the exception of one previously reported cSNP, all of the identified changes were novel. The frequency of polymorphisms differed significantly by ethnicity and several appeared to be in linkage disequilibrium. None of the changes appeared likely to be of functional significance, thus suggesting that changes in the genomic NMDAR1 are unlikely to contribute to the etiology of schizophrenia. Estimates of nucleotide diversity are comparable to those observed in studies of other genes.
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PMID:Identification of single nucleotide polymorphisms (SNPs) and other sequence changes and estimation of nucleotide diversity in coding and flanking regions of the NMDAR1 receptor gene in schizophrenic patients. 1132 95

Schizophrenia is a common, genetically heterogeneous disorder with a lifetime prevalence of approximately 1% in the general population. Linkage studies of affected families have now strongly implicated a susceptibility locus on chromosome 8p21-22. Tests of allelic association with markers on 8p21-22 should be able to localise any quantitative trait nucleotides (QTN's) or susceptibility mutations to within a few hundred kilobases. Three brain expressed candidate susceptibility genes, prepronociceptin (PNOC), neuronal cholinergic receptor, nicotinic, alpha polypeptide 2 (CHRNA2) and arylamine N-acetyltransferase 1 (NAT1) have been mapped to chromosome 8p21-22. A case-control, allelic association study was performed using a novel highly polymorphic dinucleotide repeat, D8S2611 near the PNOC gene, two previously characterised dinucleotide repeats, D8S131 and D8S131P at the CHRNA2 locus and an RFLP at the 3'UTR of the arylamine N-acetyltransferase 1 (NAT1) gene. No differences were found in allele frequencies between the patient and control groups. DNA variations or mutations at or near the three genes under study are unlikely to increase susceptibility to schizophrenia in our population sample.
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PMID:Genetic association studies of schizophrenia using the 8p21-22 genes: prepronociceptin (PNOC), neuronal nicotinic cholinergic receptor alpha polypeptide 2 (CHRNA2) and arylamine N-acetyltransferase 1 (NAT1). 1143 30

The glial cell line-derived neurotrophic factor (GDNF) is an important neurotrophic and potential differentiation factor for dopaminergic systems. Both the dopamine theory and the neurodevelopmental hypothesis of schizophrenia suggest that alterations of GDNF functions could be involved in the pathogenesis of schizophrenia. Using polymerase chain reaction and single strand conformational polymorphism analysis, we searched for polymorphisms in the GDNF gene in 50 patients with schizophrenia. No evidence was obtained, however, for the presence of polymorphisms in the DNA sequence encoding GDNF mature peptide in our patients. We then examined a trinucleotide repeat (AGG)(n) polymorphism in the 3'-UTR of the GDNF gene for allelic association in a Japanese sample of 99 schizophrenic patients and 98 control subjects. There was no significant difference in the overall distribution of the allele between the two groups. When each allele was examined separately, the allele (AGG)(10) was more common in schizophrenic patients than in control subjects, but this finding was not significant when multiple testing was taken into account in the analysis. Overall, we obtained no solid evidence for the involvement of the GDNF gene in the pathogenesis of schizophrenia, although further studies in larger numbers of subjects will be required to conclude whether the trinucleotide repeat polymorphism is associated with the development of schizophrenia.
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PMID:Glial cell line-derived neurotrophic factor (GDNF) gene and schizophrenia: polymorphism screening and association analysis. 1160 Jan 85

Recently, a Leu309Met mutation in WKL1 (MLC1, KIAA0027), a gene mapped to chromosome 22q13.33, was reported to co-segregate with periodic catatonia, a clinical sub-type of schizophrenia, in seven members of an extended pedigree.(1) WKL1 encodes a putative membrane protein expressed exclusively in the brain, particularly in the amygdala, nucleus caudatus, thalamus, and hippocampus.(1) We screened WKL1 for etiologic mutations in 28 probands from the United States who were given a consensus diagnosis of schizophrenia and met at least one of these criteria: (1) were from multiplex schizophrenia families where at least two schizophrenic subjects were reported to display catatonic behavior at sometime during the course of their illness; or (2) were from multiplex schizophrenia families where, in a genome scan for schizophrenia susceptibility loci, evidence for excess allele sharing among affected family members for markers in the 22q13 region was seen. In addition, 15 affected subjects from 15 German pedigrees were similarly screened for causative mutations. This German cohort exhibited the catatonia phenotype but had ambiguous linkage to 22q13 and included the mutation-positive proband as a positive control. The 43 probands were screened for base changes in WKL1: 15 SNPs in the non-coding regions of the gene, three SNPs in the 3'UTR, four synonymous coding SNPs and two non-synonymous (amino acid changing) SNPs were identified. We were able to rapidly confirm the Leu309Met nucleotide change in the positive control. No missense mutations were detected in any of the other 42 probands studied. These data exclude the role of WKL1 in schizophrenia susceptibility in the subjects studied.
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PMID:No missense mutation of WKL1 in a subgroup of probands with schizophrenia. 1198 87

The dopamine D(3) receptor gene (DRD3) is a candidate for a number of psychiatric conditions including schizophrenia, bipolar disorder and alcohol and drug abuse. Previous studies have reported associations between polymorphisms in DRD3 and these disorders, but these findings may have reflected linkage disequilibrium with pathogenic variants that are further upstream. We have isolated and sequenced approximately 9 kb of genomic sequence upstream of the human DRD3 translational start site. Using 5' RACE, we have identified within this region three additional exons and two putative promoter regions which show promoter activity in three different cell lines. A 5' UTR identified only in lymphoblasts is spread over three exons and is 353 bp long. A second 5' UTR, found in adult and fetal brain, lymphocytes, kidney and placenta is spread over two exons and is 516 bp long. A 260-bp sequence within this 9 kb corresponds to a previously reported EST, but corresponding mRNA could not be found in the tissues above. The EST, 5' UTRs and putative promoter regions have been analysed for polymorphisms, revealing 10 single nucleotide polymorphisms, seven of which were tested for association in a large sample of unrelated patients with schizophrenia and matched controls. No associations were observed with schizophrenia. In addition we failed to replicate previous findings of association with homozygosity of the Ser9Gly variant. The results from this study imply that neither the coding nor the regulatory region of DRD3 plays a major role in predisposition to schizophrenia.
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PMID:Characterisation, mutation detection, and association analysis of alternative promoters and 5' UTRs of the human dopamine D3 receptor gene in schizophrenia. 1208 67


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