Gene Expression Profiling in Brodmann's Area 46 from Subjects with Schizophrenia

Dean, Brian; Keriakous, Dahlia; Scarr, Elizabeth; Thomas, Elizabeth A.

doi:10.1080/00048670701213245

Cited by 78 publications

(61 citation statements)

References 56 publications

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“…In our study, we found that two housekeeper genes β-Actin and GADPH mRNAs which do not differ between people with schizophrenia compared to control as previously found ( [58], [59]) and our data suggests that both are particularly stable mRNAs and useful housekeeping control genes for our postmortem human brain studies. However, if should be emphasized that the utility of GADPH as a control varies from brain collection to brain collection as some laboratories find GADPH to be stable and to not differ in people with schizophrenia as compared to controls as we do ( [60], [59]), while others suggest that is one of the least stable and thus least reliable control genes ( [22], [61]).…”

Section: Discussionsupporting

confidence: 84%

Selection of Reference Gene Expression in a Schizophrenia Brain Cohort

Rothmond

Fung

Wong

et al. 2010

Schizophrenia Research

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Section: Discussionsupporting

confidence: 84%

Selection of Reference Gene Expression in a Schizophrenia Brain Cohort

Rothmond

Fung

Wong

et al. 2010

Schizophrenia Research

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“…However, the mechanism by which DISC1 contributes to the pathophysiology of schizophrenia remains unknown. Although reduced expression of DISC1 mRNA was found in lymphoblastoid cell lines of family members with the translocation (26) and in bipolar disorder patients with a putative risk-associated haplotype (27), no changes were detected in the brain tissue of unrelated patients with schizophrenia or in individuals carrying risk-associated genotypes (28)(29)(30). The evidence from a variety of studies in cell and animal models as well as in human brain tissue suggests that DISC1 mRNA and/or protein processing is complex, and it therefore is plausible that changes in gene processing occur in patients who have major mental illness (28,(31)(32)(33)(34)(35)(36).…”

mentioning

confidence: 88%

DISC1 splice variants are upregulated in schizophrenia and associated with risk polymorphisms

Nakata

Lipska

Hyde

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

163

146

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Disrupted-In-Schizophrenia-1 (DISC1) is a promising susceptibility gene for major mental illness, but the mechanism of the clinical association is unknown. We searched for DISC1 transcripts in adult and fetal human brain and tested whether their expression is altered in patients with schizophrenia and is associated with genetic variation in DISC1. Many alternatively spliced transcripts were identified, including groups lacking exon 3 (⌬3), exons 7 and 8 (⌬7⌬8), an exon 3 insertion variant (extra short variant-1, Esv1), and intergenic splicing between TSNAX and DISC1. Isoforms ⌬7⌬8, Esv1, and ⌬3, which encode truncated DISC1 proteins, were expressed more abundantly during fetal development than during postnatal ages, and their expression was higher in the hippocampus of patients with schizophrenia. Schizophrenia risk-associated polymorphisms [non-synonymous SNPs rs821616 (Cys704Ser) and rs6675281 (Leu607Phe), and rs821597] were associated with the expression of ⌬3 and ⌬7⌬8. Moreover, the same allele at rs6675281, which predicted higher expression of these transcripts in the hippocampus, was associated with higher expression of DISC1⌬7⌬8 in lymphoblasts in an independent sample. Our results implicate a molecular mechanism of genetic risk associated with DISC1 involving specific alterations in gene processing.alternative splicing ͉ genetic ͉ hippocampus ͉ psychiatric illness S chizophrenia is a common mental disorder with a lifetime prevalence of Ϸ 1% (1). It has been assumed, on the basis of evidence from twin, family, and adoption studies, that genetic factors play a strong etiologic role in schizophrenia (2, 3). The genetic predisposition is likely to be determined by a complex network of interactions between genes and environmental risk factors (4).The Disrupted-In-Schizophrenia-1 (DISC1) gene was identified as a potential susceptibility gene for mental disorders based on studies of a chromosomal translocation found in a large Scottish family that had a high frequency of schizophrenia and other psychiatric disorders, including bipolar disorder and major depression (5-7). Although the translocation identified in the Scottish family has not been observed in any other families, independent support for involvement of DISC1 in the etiology of mental illness has come from a number of genetic linkage and association studies in diverse populations (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Although the specific SNPs, alleles, and haplotypes have varied across these studies, raising issues of allelic and populations heterogeneity, the overall evidence implicates DISC1 as a promising candidate susceptibility gene for schizophrenia. However, the mechanism by which DISC1 contributes to the pathophysiology of schizophrenia remains unknown. Although reduced expression of DISC1 mRNA was found in lymphoblastoid cell lines of family members with the translocation (26) and in bipolar disorder patients with a putative risk-associated haplotype (27), no changes were detected in the brain tissue of unre...

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“…We were particularly interested in CNTNAP2 and PCDH17, because variation in CNTNAP2 has been linked to language and autism spectrum disorders (29,30), and PCDH17 expression was recently suggested to be increased in the prefrontal cortex in a cohort of schizophrenic subjects (31). In sharp contrast to the regionally restricted distribution observed for human CNTNAP2, expression in the developing mouse brain was broad (Fig.…”

Section: In Situ Hybridization Highlights Regionally Restricted Exprementioning

confidence: 99%

Genome-wide analyses of human perisylvian cerebral cortical patterning

Abrahams

Tentler

Perederiy

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

186

183

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Despite the well established role of the frontal and posterior perisylvian cortices in many facets of human-cognitive specializations, including language, little is known about the developmental patterning of these regions in the human brain. We performed a genome-wide analysis of human cerebral patterning during midgestation, a critical epoch in cortical regionalization. A total of 345 genes were identified as differentially expressed between superior temporal gyrus (STG) and the remaining cerebral cortex. Gene ontology categories representing transcription factors were enriched in STG, whereas cell-adhesion and extracellular matrix molecules were enriched in the other cortical regions. Quantitative RT-PCR or in situ hybridization was performed to validate differential expression in a subset of 32 genes, most of which were confirmed. LIM domain-binding 1 (LDB1), which we show to be enriched in the STG, is a recently identified interactor of LIM domain only 4 (LMO4), a gene known to be involved in the asymmetric pattering of the perisylvian region in the developing human brain. Protocadherin 17 (PCDH17), a neuronal cell adhesion molecule, was highly enriched in focal regions of the human prefrontal cortex. Contactin associated protein-like 2 (CNTNAP2), in which mutations are known to cause autism, epilepsy, and language delay, showed a remarkable pattern of anterior-enriched cortical expression in human that was not observed in mouse or rat. These data highlight the importance of expression analysis of human brain and the utility of cross-species comparisons of gene expression. Genes identified here provide a foundation for understanding molecular aspects of human-cognitive specializations and the disorders that disrupt them.cortex ͉ microarray ͉ gene expression ͉ evolution ͉ CASPR2

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Gene Expression Profiling in Brodmann's Area 46 from Subjects with Schizophrenia

Cited by 78 publications

References 56 publications

Selection of Reference Gene Expression in a Schizophrenia Brain Cohort

Selection of Reference Gene Expression in a Schizophrenia Brain Cohort

DISC1 splice variants are upregulated in schizophrenia and associated with risk polymorphisms

Genome-wide analyses of human perisylvian cerebral cortical patterning

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