RGD Reference Report - Evidence implicating BRD1 with brain development and susceptibility to both schizophrenia and bipolar affective disorder. - Rat Genome Database

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Evidence implicating BRD1 with brain development and susceptibility to both schizophrenia and bipolar affective disorder.

Authors: Severinsen, JE  Bjarkam, CR  Kiaer-Larsen, S  Olsen, IM  Nielsen, MM  Blechingberg, J  Nielsen, AL  Holm, IE  Foldager, L  Young, BD  Muir, WJ  Blackwood, DH  Corydon, TJ  Mors, O  Borglum, AD 
Citation: Severinsen JE, etal., Mol Psychiatry. 2006 Dec;11(12):1126-38. Epub 2006 Aug 22.
RGD ID: 9586096
Pubmed: PMID:16924267   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.mp.4001885   (Journal Full-text)

Linkage studies suggest that chromosome 22q12-13 may contain one or more shared susceptibility genes for schizophrenia (SZ) and bipolar affective disorder (BPD). In a Faeroese sample, we previously reported association between microsatellite markers located at 22q13.31-qtel and both disorders. The present study reports an association analysis across five genes (including 14 single nucleotide and two microsatellite polymorphisms) in this interval using a case-control sample of 162 BPD, 103 SZ patients and 200 controls. The bromodomain-containing 1 gene (BRD1), which encodes a putative regulator of transcription showed association with both disorders with minimal P-values of 0.0046 and 0.00001 for single marker and overall haplotype analysis, respectively. A specific BRD1 2-marker 'risk' haplotype showed a frequency of approximately 10% in the combined case group versus approximately 1% in controls (P-value 2.8 x 10(-7)). Expression analysis of BRD1 mRNA revealed widespread expression in mammalian brain tissue, which was substantiated by immunohistochemical detection of BRD1 protein in the nucleus, perikaryal cytosol and proximal dendrites of the neurons in the adult rat, rabbit and human CNS. Quantitative mRNA analysis in developing fetal pig brain revealed spatiotemporal differences with high expression at early embryonic stages, with intense nuclear and cytosolar immunohistochemical staining of the neuroepithelial layer and early neuroblasts, whilst more mature neurons at later embryonic stages had less nuclear staining. The results implicate BRD1 with SZ and BPD susceptibility and provide evidence that suggests a role for BRD1 in neurodevelopment.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
bipolar disorder susceptibilityIAGP 9586096DNA more ...RGD 
bipolar disorder susceptibilityISOBRD1 (Homo sapiens)9586096; 9586096DNA more ...RGD 
schizophrenia susceptibilityIAGP 9586096DNA more ...RGD 
schizophrenia susceptibilityISOBRD1 (Homo sapiens)9586096; 9586096DNA more ...RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
dendrite  IDA 9586096 RGD 
perikaryon  IDA 9586096 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Brd1  (bromodomain containing 1)

Genes (Mus musculus)
Brd1  (bromodomain containing 1)

Genes (Homo sapiens)
BRD1  (bromodomain containing 1)


Additional Information