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)

Evidence for a pseudoautosomal locus for a schizophrenia susceptibility gene was sought by two forms of analysis of 25 multiply affected families. Firstly, in the sample as a whole there was an excess of same-sex over mixed-sex siblings compared with that expected. Secondly, linkage analysis was performed in six of the families. The genotypes were studied for DXYS14, a highly polymorphic marker in the telomeric pseudoautosomal region. No evidence for positive linkage was found with two-point analysis under eight different genetic models for the mode of transmission. A non-parametric, sibling-pair analysis also failed to detect linkage. Our findings provide no evidence for linkage within the pseudoautosomal region; same-sex concordance must arise from some other mechanism.
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PMID:No evidence for a pseudoautosomal locus for schizophrenia. Linkage analysis of multiply affected families. 163 31

A susceptibility locus for schizophrenia in the 'pseudo-autosomal' region has been proposed on the basis of the reported excess of sex-chromosome aneuploidies (e.g. XXY and XXX) among patients with schizophrenia and the finding that schizophrenic sib-pairs are more often of the same than of the opposite sex. This hypothesis has been tested in 83 sibships with two or more siblings fulfilling Research Diagnostic Criteria for schizophrenia or schizoaffective disorder. Alleles at the pseudo-autosomal telomeric locus DXYS14, which is unlinked with sex, were analysed using the method of affected sib-pairs. Affected sibs shared alleles at DXYS14 more frequently than expected by random Mendelian assortment, supporting genetic linkage between DXYS14 and schizophrenia.
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PMID:Evidence for a pseudo-autosomal locus for schizophrenia using the method of affected sibling pairs. 186 17

The hypothesis that the gene for schizophrenia is located in the pseudoautosomal region of the sex chromosomes predicts that same-sex concordance will occur in paternally rather than maternally derived pairs. In 120 families that included at least one sibling pair with schizophrenia, affected members were significantly more likely to be of the same sex when there was a history of illness on the paternal than on the maternal side, the difference remaining significant when parent of origin was assessed by three different methods. The finding is as predicted by the pseudoautosomal hypothesis: therefore a search for the gene should be focused on this small (three megabase) region of the genome. The ratio of same to mixed sex pairs in paternally-derived cases (approximately 3:1) suggests the gene is located in the centromeric one-third of the pseudoautosomal region.
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PMID:Concordance by sex in sibling pairs with schizophrenia is paternally inherited. Evidence for a pseudoautosomal locus. 234 43

Several lines of evidence suggest that the sex chromosomes have a role in the expression of schizophrenia. Gender differences in response to treatment, age at onset of illness, and prognosis indicate an influence of sex in differential expression of schizophrenia. On the basis of a higher-than-expected concordance for sex among siblings with schizophrenia, as well as the findings of cytogenetic abnormalities of the sex chromosomes in some schizophrenia patients, a pseudoautosomal location for a schizophrenia susceptibility locus has been proposed. To test this hypothesis, we investigated genetic linkage of the pseudoautosomal region to schizophrenia in a large Swedish kindred. Using pairwise analyses we tested eight markers spanning the most telomeric region to the boundary of the sex-specific region. In addition, we used multi-point analysis with five markers spanning the region to test for the presence of a schizophrenia susceptibility locus in the pseudoautosomal region. No evidence was found for linkage to schizophrenia under the given genetic model: "autosomal" dominant, f (penetrance) = 0.72, q (gene frequency) = 0.02, phenocopies = 0.001.
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PMID:Linkage study of a susceptibility locus for schizophrenia in the pseudoautosomal region. 808 32

The two most consistent features of the diseases caused by trinucleotide repeat expansion-neuropsychiatric symptoms and the phenomenon of genetic anticipation-may be present in forms of dementia, hereditary ataxia, Parkinsonism, bipolar affective disorder, schizophrenia and autism. To identify candidate genes for these disorders, we have screened human brain cDNA libraries for the presence of gene fragments containing polymorphic trinucleotide repeats. Here we report the cDNA cloning of CAGR1, originally detected in a retinal cDNA library. The 2743 bp cDNA contains a 1077 bp open reading frame encoding 359 amino acids. This amino acid sequence is homologous (56% amino acid identify and 81% amino acid conservation) to the Caenorhabditis elegans cell fate-determining protein mab-21. CAGR1 is expressed in several human tissues, most prominently in the cerebellum, as a message of approximately 3.0 kb. The gene was mapped to 13q13, just telomeric to D13S220. A 5'-untranslated CAG trinucleotide repeat is highly polymorphic, with repeat length ranging from six to 31 triplets and a heterozygosity of 87-88% in 684 chromosomes from several human populations. One allele from an individual with an atypical movement disorder and bipolar affective disorder type II contains 46 triplets, 15 triplets longer than any other allele detected. Though insufficient data are available to link the long repeat to this clinical phenotype, an expansion mutation of the CAGR1 repeat can be considered a candidate for the etiology of disorders with anticipation or developmental abnormalities, and particularly any such disorders linked to chromosome 13.
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PMID:cDNA cloning of a human homologue of the Caenorhabditis elegans cell fate-determining gene mab-21: expression, chromosomal localization and analysis of a highly polymorphic (CAG)n trinucleotide repeat. 873 27

Alterations in dopamine neurotransmission and disturbed norepinephrine activity have been implicated in the pathogenesis of schizophrenia. We considered the dopamine-beta-hydroxylase (DBH) gene located on the long arm of chromosome 9 (9q34.3) as a candidate gene for schizophrenia. DBH catalyzes the synthesis of norepinephrine from dopamine in noradrenergic neurons. In addition to DBH we used in the linkage study DNA markers ABL (centromeric) and D9S114 (telomeric). The aim of this study was to test linkage and association between PCR-based genotyped markers and schizophrenia. A simulation was done to investigate the power of our sample. In 34 Austrian families we could not detect linkage between schizophrenia and schizophrenia spectrum disorders and the three genetic markers. We could not find any significant deviation in allelic or genotypic distribution from expectations. Based on our results we conclude that the DBH gene seems to have no strong contribution in the etiology of schizophrenia.
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PMID:Schizophrenia and the dopamine-beta-hydroxylase gene: results of a linkage and association study. 892 53

The difficulties in defining the borders of the schizophrenia spectrum is one major source of variance in linkage studies of schizophrenia. The employment of biological markers may prove advantageous. Due to empirical evidence, eye tracking dysfunction (ETD) has been discussed to be the most promising marker for genetic liability to schizophrenia. With respect to the recent progress in genomic scans, which have pointed to the short arm of chromosome 6, we carried out a scan of the 6p21-23 region with 16 microsatellite markers to test for linkage between chromosomal markers and ETD as well as schizophrenia. We tested 5 models of inheritance of ETD and found maximum two-point lod scores of 3.51 for D6S271 and 3.44 for D6S282. By including these markers in a multipoint analysis, a lod score of 4.02 was obtained. In the case of schizophrenia, 7 models were tested; however, with non-significant results. Our findings, together with another recent linkage report, point to the possibility of a second susceptibility locus for schizophrenia which may be located centromeric to the HLA region. Also, the evidence of ETD being a susceptibility marker for schizophrenia receives further support.
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PMID:Eye tracking dysfunction is a putative phenotypic susceptibility marker of schizophrenia and maps to a locus on chromosome 6p in families with multiple occurrence of the disease. 895 Apr 16

We have investigated whether there is a locus on chromosome 6 that confers an increased susceptibility to schizophrenia using a two-stage approach and nonparametric linkage analysis. Allele sharing identical by descent (IBD) and multipoint maximum likelihood score (MLS) statistics were employed. Results from two tested data sets, a first data set, or genome scanning data set, and a second replication data set, show excess allele sharing for multiple markers in 6q, a chromosomal region not previously reported as linked to schizophrenia. In our genome scanning data set, excess allele sharing was found for markers on 6q13-q26. The greatest allele sharing was at interval 6q21-q22.3 at marker D6S416 (IBD percentage 69; P = 0.00024). The multipoint MLS values were greater than 2.4 in the 11.4-cM interval delimited by D6S301 and D6S303, with a maximum value of 3.06 close to D6S278 and of 3.05 at D6S454/D6S423. We did not confirm, however, the previously described linkage in 6p, when tested in the systematic genome scanning data set. The replication data set also showed excess allele sharing in chromosomal area 6q13-q26, which overlapped with the aforementioned positive linkage area of the genome scanning data set. The highest sharing of the second data set was at D6S424 (IBD percentage 64; P = 0.0004), D6S283 (IBD percentage 62; P = 0.0009), and D6S423 (IBD percentage 63; P = 0.0009). Multipoint MLS analysis yielded MLS values greater than 1 in an area of about 35 cM, which overlaps with the MLS multipoint area of linkage from the genome scanning data set. The multipoint MLS at the D6S454/D6S423 locus was 2.05. In the second data set, the maximum multipoint MLS was located about 10 cM centromeric from the maximum of the genome scanning data set, at the interval D6S424-D6S275 (2.35). Our results provide very suggestive evidence for a susceptibility locus for schizophrenia in chromosome 6q from two independent data sets.
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PMID:Suggestive evidence for a schizophrenia susceptibility locus on chromosome 6q and a confirmation in an independent series of pedigrees. 922 66

A VNTR for the human dopamine transporter gene (DAT-1) has been localized to chromosome 5p15.3. Silverman et al. [1996] found evidence for genetic linkage of the D5S111 locus, located just centromeric to DAT-1, to schizophrenia and related disorders in a large Hispanic family. We evaluated five markers on 5p, including D5S111 and the DAT-1 VNTR, in five multiplex schizophrenic families, assuming autosomal dominant transmission (subjects assessed n = 122, DNAs available n = 96, individuals with schizophrenia and schizoaffective disorder n = 36, broader spectrum disorders n = 14). LOD scores were negative across all families for all markers tested, and overall LOD scores were strongly negative (<-2.0, theta = 0) across all five families for each of the markers typed. Thus, there is no evidence to support the linkage of markers in this region of chromosome 5 to schizophrenia in this sample of families.
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PMID:Absence of linkage for schizophrenia on the short arm of chromosome 5 in multiplex Canadian families. 934 93

The finding by Straub et al. (1995) on 6p22-24 is one of the strongest reports so far in psychiatric genetics. It appears to be substantially replicated by Schwab and collaborators (1995; 1997), and to a lesser extent by Moises et al. (1995). Still, this data does not fulfill the criteria of Lander and Kruglyak (1995) for a confirmed finding in complex disease. There are a number of data sets that do not appear to show linkage. Further genotyping work needs to be done in this area and additional markers in the area would be helpful in the available data sets. It should be noted that the Straub and Kendler dataset (Straub et al., 1995, 1997; Kendler et al., 1996), with 754 affecteds, is substantially larger than any other, and should be weighted concomitant with this. Still, additional data will be necessary before the finding may be firmly accepted. Candidate gene studies have started in this area. The SCA locus is promising on theoretical grounds, but has been only weakly positive in two studies so far. The HLA locus is interesting in relation to autoimmune theories of schizophrenia. There is a long history of HLA studies in schizophrenia with mixed results. HLA is located centromeric to the major positive region identified by Straub, but perhaps not too far to be considered a candidate region. Family-based association studies will be necessary to clarify whether there is a true association in this area. The location identified by Cao et al. (1997) on 6q is promising. Straub and Kendler's data set has been partially tested in this region with negative results. Gejman and co-workers (1997) have recently reported additional positive data in this region from Levinson and Mowry. Additional studies in this area are indicated.
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PMID:Chromosome 6 workshop. 968 28


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