Systematic screening of the 14-3-3 eta (?) chain gene for polymorphic variants and case-control analysis in schizophrenia

Bell, Rachel; Munro, Janet; Russ, Carsten; Powell, John; Bruinvels, Anne T.; Kerwin, Robert; Collier, David

doi:10.1002/1096-8628(20001204)96:6<736::aid-ajmg8>3.0.co;2-2

Cited by 39 publications

(29 citation statements)

References 46 publications

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“…30 This isoform has also been reported to be associated with schizophrenia in two previous case-control studies by other groups. 22,31 The mean age of the Toronto and Portuguese subjects was 34.3 and 33.6 years, respectively, and the mean age of onset (when available) was 19.6 and 22.1 years, respectively. For the combined sample, the mean age was 33.9 years and the mean age of onset was 21.1 years.…”

Section: Genetic Association Resultsmentioning

confidence: 99%

“…Among several polymorphisms detected and investigated, they found an association between schizophrenia and an exon 1 SNP, in a case-control study of 220 subjects. 22 A diagram of these polymorphisms in the 14-3-3Z gene is shown in Figure 1.…”

Section: Discussionmentioning

confidence: 99%

“…22 A 303 bp amplicon was amplified using the primers (forward) 5 0 -ctt agc caa aca agc ctt cg and (reverse) 5 0 -ttc cca aga gac agg agt gc. After denaturing at 951C for 5 min, 35 cycles of PCR in a Perkin-Elmer GeneAmp PCR system 9700 were performed under the following conditions: 941C Â 30 s, 581C Â 45 s, 721C Â 45 s. Extension of the reaction was at 721C for 7 min.…”

Section: -3-3z Genotypingmentioning

confidence: 99%

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Identification of candidate genes for psychosis in rat models, and possible association between schizophrenia and the 14-3-3η gene

et al. 2003

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Although the genetic contribution to schizophrenia is substantial, positive findings in wholegenome linkage scans have not been consistently replicated. We analyzed gene expression in various rat conditions to identify novel candidate genes for schizophrenia. Suppression subtraction hybridization (SSH), with polyA mRNA from temporal and frontal cortex of rats, was used to identify differentially expressed genes. Expression of mRNA was compared between adult Lewis and Fischer 344 (F344) rats, adult and postnatal day 6 (d6) F344, and adult F344 treated with haloperidol or control vehicle. These groups were chosen because each highlights a particular aspect of schizophrenia: differences in strain vulnerability to behavioral analogs of psychosis; factors that may relate to disease onset in relation to CNS development; and improvement of symptoms by haloperidol. The 14-3-3 gene family, as represented by 14-3-3c and 14-3-3f isoforms in the SSH study, and SNAP-25 were among the candidate genes. Genetic association between schizophrenia and the 14-3-3g gene, positioned close to a genomic locus implicated in schizophrenia, and SNAP-25 genes was analyzed in 168 schizophrenia probands and their families. These findings address three different genes in the 14-3-3 family. We find a significant association with schizophrenia for two polymorphisms in the 14-3-3g gene: a 7 bp variable number of tandem repeats in the 5 0 noncoding region (P ¼ 0.036, 1 df), and a 3 0 untranslated region SNP (753G/A) that is an RFLP visualized with Ava II (P ¼ 0.028). There was no significant genetic association with SNAP-25. The candidate genes identified may be of functional importance in the etiology, pathophysiology or treatment response of schizophrenia or psychotic symptoms. This is to our knowledge the first report of a significant association between the 14-3-3g-chain gene and schizophrenia in a family-based sample, strengthening prior association reports in case-control studies and microarray gene expression studies.

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Section: Genetic Association Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: -3-3z Genotypingmentioning

confidence: 99%

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Identification of candidate genes for psychosis in rat models, and possible association between schizophrenia and the 14-3-3η gene

et al. 2003

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“…There is evidence for genetic association of the 14-3-3Z and z genes with schizophrenia. [186][187][188][189] Moreover, expression of several 14-3-3 genes is decreased in PFC of patients with schizophrenia. 190 In addition, expression of some 14-3-3 genes is sensitive to drugs used to treat psychiatric illness, since 14-3-3b is upregulated in PFC of monkeys treated with the neuroleptic haloperidol 190 and levels of 14-3-3d and 14-3-3z are altered in rat cortical neurons in response to application of the antidepressant fluoxetine.…”

Section: Lis1 Ndel1 Nde1 and Disc1mentioning

confidence: 99%

The DISC locus in psychiatric illness

et al. 2007

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The DISC locus is located at the breakpoint of a balanced t(1;11) chromosomal translocation in a large and unique Scottish family. This translocation segregates in a highly statistically significant manner with a broad diagnosis of psychiatric illness, including schizophrenia, bipolar disorder and major depression, as well as with a narrow diagnosis of schizophrenia alone. Two novel genes were identified at this locus and due to the high prevalence of schizophrenia in this family, they were named Disrupted-in-Schizophrenia-1 (DISC1) and Disrupted-in-Schizophrenia-2 (DISC2). DISC1 encodes a novel multifunctional scaffold protein, whereas DISC2 is a putative noncoding RNA gene antisense to DISC1. A number of independent genetic linkage and association studies in diverse populations support the original linkage findings in the Scottish family and genetic evidence now implicates the DISC locus in susceptibility to schizophrenia, schizoaffective disorder, bipolar disorder and major depression as well as various cognitive traits. Despite this, with the exception of the t(1;11) translocation, robust evidence for a functional variant(s) is still lacking and genetic heterogeneity is likely. Of the two genes identified at this locus, DISC1 has been prioritized as the most probable candidate susceptibility gene for psychiatric illness, as its protein sequence is directly disrupted by the translocation. Much research has been undertaken in recent years to elucidate the biological functions of the DISC1 protein and to further our understanding of how it contributes to the pathogenesis of schizophrenia. These data are the main subject of this review; however, the potential involvement of DISC2 in the pathogenesis of psychiatric illness is also discussed. A detailed picture of DISC1 function is now emerging, which encompasses roles in neurodevelopment, cytoskeletal function and cAMP signalling, and several DISC1 interactors have also been defined as independent genetic susceptibility factors for psychiatric illness. DISC1 is a hub protein in a multidimensional risk pathway for major mental illness, and studies of this pathway are opening up opportunities for a better understanding of causality and possible mechanisms of intervention. Molecular Psychiatry (2008) 13, 36-64; doi:10.1038/sj.mp.4002106; published online 2 October 2007 Keywords: schizophrenia; bipolar disorder; depression; DISC1; DISC2; mouse models Genetics of DISC1 discoverySt Clair et al. 1 first reported a Scottish family with a high loading of major mental illness, which cosegregates with a t(1;11) translocation. Long-term follow-up of this family over a period of 30 years has reported 87 family members, of whom 37 carry the translocation. 2 Of 29 individuals carrying the translocation, for whom psychiatric assessment was possible, 7 have a diagnosis of schizophrenia, 1 has a diagnosis of bipolar disorder and 10 cases of recurrent major depression were also reported. 2 Thus, 18 of 29 translocation carriers are diagnosed with major mental illness whereas none of...

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“…Bell at al. [121] performed a systematic single-strand conformation polymorphism screen of this gene and found 12 potential variations, including the 5′ VNTR that was evaluated in the Japanese study. One variant in the untranslated region of exon 1 (408T>G) was found to occur more frequently in schizophrenics than controls (p = 0.01), though significance was reduced after fivefold correction for multiple testing.…”

Section: Chromosome 22mentioning

confidence: 99%

Recent advances in the genetics of schizophrenia

Waterworth¹,

Bassett

Brzustowicz³

2002

CMLS, Cell. Mol. Life Sci.

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The genetic etiology of schizophrenia, a common and debilitating psychiatric disorder, is supported by a wealth of data. Review of the current findings suggests that considerable progress has been made in recent years, with a number of chromosomal regions consistently implicated by linkage analysis. Three groups have shown linkage to 1q21-22 using similar models, with HLOD scores of 6.5, 3.2, and 2.4. Other replicated loci include 13q32 that has been implicated by two independent groups with significant HLOD scores (4.42) or NPL values (4.18), and 5p14.1-13.1, 5q21-33, 8p21-22, and 10p11-15, each of which have been reported as suggestive by at least three separate groups. Different studies have also replicated evidence for a modest number of candidate genes that were not ascertained through linkage. Of these, the greatest support exists for the DRD3 (3q13.3), HTR2A (13q14.2), and CHRNA7 (15q13-q14) genes. The refinement of phenotypes, the use of endophenotypes, reduction of heterogeneity, and extensive genetic mapping have all contributed to this progress. The rapid expansion of information from the human genome project will likely further accelerate this progress and assist in the discovery of susceptibility genes for schizophrenia. A greater understanding of disease mechanisms and the application of pharmacogenetics should also lead to improvements in therapeutic interventions.

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Systematic screening of the 14-3-3 eta (?) chain gene for polymorphic variants and case-control analysis in schizophrenia

Cited by 39 publications

References 46 publications

Identification of candidate genes for psychosis in rat models, and possible association between schizophrenia and the 14-3-3η gene

Identification of candidate genes for psychosis in rat models, and possible association between schizophrenia and the 14-3-3η gene

The DISC locus in psychiatric illness

Recent advances in the genetics of schizophrenia

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