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)

Trinucleotide microsatellites are widespread in the human and other mammalian genomes. Expansions of unstable trinucleotide repeats have been associated so far with a number of different genetic diseases including fragile X, myotonic dystrophy (DM) and Huntington disease. While ten possible trinucleotides can occur at the DNA level, only CTG and CCG repeats are involved in the disorders described so far. However, the repeat expansion detection (RED) technique has identified additional large repeats of ATG, CCT, CTT, and TGG of potentially pathological significance in the human genome. We now show that conclusive information about the chromosomal localization of long trinucleotide repeats can be achieved in a relatively short time using fluorescence in situ hybridization (FISH) with biotin-labelled trinucleotide polymers. Large CTG expansions (> 1 kb) in DM and an unstable (CTG)306 repeat in a patient with schizophrenia were detected by eye through the microscope without electronic enhancement. Digital imaging was used to analyse the chromosomal distribution of long CCA and AGG repeats. Our results suggest that long trinucleotide repeats occur in the normal human genome and that the size of individual repeat loci may be polymorphic.
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PMID:Chromosomal localization of long trinucleotide repeats in the human genome by fluorescence in situ hybridization. 856 57

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

Association studies on gene polymorphisms of neurotransmitter systems have hypothesized an involvement of dopamine receptors in susceptibility to schizophrenia. However, structural and morphological abnormalities in different brain regions of schizophrenic patients support neurodevelopmental etiology for schizophrenia and neurotrophic factor genes could be candidates for genetic studies. The glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic and potential differentiation factor for dopaminergic systems. We have performed, in an Italian sample, an association study on 3' UTR (AGG)n repeat in GDNF gene. Our results have evidenced a difference in the allele frequencies between patients and controls (CLUMP (T1) chi2 = 17.365, df = 9, P = 0.043) and the (AGG)n > or = 15 alleles (Fisher Exact Test (two side) chi2 = 11.818, df = 1, P = 0.0003) were more present in the controls group. Similarity, the carriers of (AGG)n > or = 15 (OR = 0.176 95% CI: 0.060-0.520) were more present in the same group. These results support that the (AGG)n > or = 15 alleles could be protective factors against schizophrenia and thus they suggest a possible involvement of GDNF gene in the genetic liability to illness.
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PMID:3' UTR (AGG)n repeat of glial cell line-derived neurotrophic factor (GDNF) gene polymorphism in schizophrenia. 1500 93

The glial cell line-derived neurotrophic factor (GDNF) gene is located within a region of chromosome 5 (5p14.1-q13.3) that has been highlighted as a potential schizophrenia susceptibility locus by a number of genome scans. GDNF is neurotrophic and is also thought to be involved in differentiation of dopaminergic neurones. The GDNF gene is, therefore, a positional and functional candidate gene for schizophrenia. It is of additional interest because altered GDNF mRNA and protein expression has been reported in response to antipsychotics and the psychotomimetic phencyclidine, and two previous studies, focussed on a single variant, have reported weak support for genetic association between GDNF and schizophrenia in small samples. To test the hypothesis that GDNF is a susceptibility gene for schizophrenia, we performed a detailed association study. We chose 9 SNPs that spanned a genomic region of 40 kb and fully encompassed GDNF. SNPs were genotyped in a sample of 673 schizophrenic patients and 716 matched controls, all of Caucasian origin and all collected from the UK or Ireland. Of the 9 SNPs genotyped 2 showed nominally significant genotypic association at the P< or =0.05 level (rs2973050; OR=1.11; P-value=0.007 and rs2910702; OR=1.14; P-value=0.039). Permutation testing to allow for multiple comparisons of non-independent markers gave a corrected genotypic P-value of 0.052 for rs2973050. We also genotyped an (AGG)(n) repeat located in the 3' UTR of the GDNF but this showed no evidence for association. We conclude that our sample does not provide independent statistically significant evidence for association between GDNF and schizophrenia, nor does it replicate previous specific reports of association.
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PMID:Association analysis of the glial cell line-derived neurotrophic factor (GDNF) gene in schizophrenia. 1789 12