ABSTRACT
We have carried out a detailed annotation of 550 kb of genomic DNA on human chromosome 21 containing the ERG and ETS2 genes. Comparative genomic analysis between this region and the interval of conserved synteny on mouse chromosome 16 indicated that the order and orientation of the ERG and ETS2 genes were conserved and revealed several regions containing potential conserved noncoding sequences. Four pseudogenes including those for small protein G, laminin receptor, human transposase protein and meningioma-expressed antigen were identified. A potentially novel gene (C21orf24) with alternative mRNA transcripts, consensus splice donor and acceptor sites, but no coding potential nor murine orthologue, was identified and found to be expressed in a range of human cell lines. We have identified four novel splice variants that arise from a previously undescribed 5' exon of the human ERG gene. Comparison of the cDNA sequences enabled us to determine the complete exon-intron structure of the ERG gene. We have also identified the presence of noncoding RNAs in the first and second introns of the ETS2 gene. Our studies have important implications for Down syndrome as this region contains multiple mRNA transcripts, both coding and potentially noncoding, that may play as yet undescribed roles in the pathogenesis of this disorder.
Subject(s)
Chromosome Mapping/methods , Chromosomes, Human, Pair 21/genetics , Chromosomes, Mammalian/genetics , DNA-Binding Proteins , Oncogene Proteins/genetics , Retroviridae Proteins, Oncogenic/genetics , Trans-Activators , Transcription Factors/genetics , Alternative Splicing , Animals , CHO Cells , Cell Line , Cell Line, Tumor , Cricetinae , DNA, Complementary/chemistry , DNA, Complementary/genetics , Exons , Female , Genes/genetics , Humans , Hybrid Cells , Introns , Jurkat Cells , K562 Cells , Molecular Sequence Data , Open Reading Frames/genetics , Pseudogenes/genetics , Sequence Analysis, DNA , Synteny , Transcriptional Regulator ERGABSTRACT
INTRODUCTION: Patients with unipolar depression show impaired performance on the Tower of London planning task. Positron emission tomography, which has previously identified resting state blood flow abnormalities in depression, was used to investigate neural activity associated with performance of this task in depressed patients and normal controls. METHODS: Six patients with unipolar depression and six matched controls were scanned while performing easy and hard Tower of London problems in a one-touch computerized paradigm and while performing a perceptuomotor control task. RESULTS: The patients in this study showed an expected task-related performance deficit compared with normal subjects. In normal subjects, the task engaged a network of prefrontal cortex, anterior cingulate, posterior cortical areas and subcortical structures including the striatum, thalamus and cerebellum. Depressed patients failed to show significant activation in the cingulate and striatum; activation in the other prefrontal and posterior cortical regions was significantly attenuated relative to controls. Crucially, patients also failed to show the normal augmentation of activation in the caudate nucleus, anterior cingulate and right prefrontal cortex associated with increasing task difficulty. CONCLUSIONS: These findings provide evidence for cingulate, prefrontal and striatal dysfunction associated with impaired task performance in depression. The present results are consistent with a central role of cingulate dysfunction in depression as well as suggesting impaired frontostriatal function.
Subject(s)
Corpus Striatum/physiopathology , Depressive Disorder/physiopathology , Frontal Lobe/physiopathology , Gyrus Cinguli/physiopathology , Neuropsychological Tests , Problem Solving/physiology , Volition/physiology , Adult , Analysis of Variance , Case-Control Studies , Cerebrovascular Circulation/physiology , Corpus Striatum/diagnostic imaging , Depressive Disorder/diagnostic imaging , Depressive Disorder/psychology , Female , Frontal Lobe/diagnostic imaging , Gyrus Cinguli/diagnostic imaging , Humans , Male , Middle Aged , Tomography, Emission-ComputedABSTRACT
BACKGROUND: The longer term prognosis of depressed patients treated with ECT is relatively unknown. We describe seven-year mortality and readmission risks for the Nottingham ECT series. METHOD: Cases were defined and subtyped using the Present State Examination (PSE). Follow-up was naturalistic. Death and readmission were ascertained using the Nottingham case register. RESULTS: The risk of death was doubled (SMR = 1.99, 95% CI = 1.34-2.84, P < 0.001). The seven-year cumulative probability of remaining without readmission was 0.27 (95% CI 0.19-0.35), being 0.79 (0.71-0.87) at 16 weeks (relapse) and 0.34 (0.24-0.44) thereafter (recurrence readmissions). Multiple regression analysis showed that delusions predicted relapse, while endogenous subtype, absence of psychomotor retardation, and previous history predicted recurrence readmissions. CONCLUSION: Index ECT treatment predicted high longer-term mortality and readmission risks. PSE/CATEGO-based subtyping identified patients most vulnerable to relapse and recurrence.
