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)

Chromosome 13 is the largest acrocentric human chromosome. It carries genes involved in cancer including the breast cancer type 2 (BRCA2) and retinoblastoma (RB1) genes, is frequently rearranged in B-cell chronic lymphocytic leukaemia, and contains the DAOA locus associated with bipolar disorder and schizophrenia. We describe completion and analysis of 95.5 megabases (Mb) of sequence from chromosome 13, which contains 633 genes and 296 pseudogenes. We estimate that more than 95.4% of the protein-coding genes of this chromosome have been identified, on the basis of comparison with other vertebrate genome sequences. Additionally, 105 putative non-coding RNA genes were found. Chromosome 13 has one of the lowest gene densities (6.5 genes per Mb) among human chromosomes, and contains a central region of 38 Mb where the gene density drops to only 3.1 genes per Mb.
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PMID:The DNA sequence and analysis of human chromosome 13. 1505 23

Much work has been done to identify susceptibility genes in schizophrenia and bipolar disorder. Several well established linkages have emerged in schizophrenia. Strongly supported regions are 6p24-22, 1q21-22, and 13q32-34, while other promising regions include 8p21-22, 6q16-25, 22q11-12, 5q21-q33, 10p15-p11, and 1q42. Genomic regions of interest in bipolar disorder include 6q16-q22, 12q23-q24, and regions of 9p22-p21, 10q21-q22, 14q24-q32, 13q32-q34, 22q11-q22, and chromosome 18. Recently, specific genes or loci have been implicated in both disorders and, crucially, replicated. Current evidence supports NRG1, DTNBP1, DISC1, DAOA(G72), DAO, and RGS4 as schizophrenia susceptibility loci. For bipolar disorder the strongest evidence supports DAOA(G72) and BDNF. Increasing evidence suggests an overlap in genetic susceptibility across the traditional classification systems that dichotomised psychotic disorders into schizophrenia or bipolar disorder, most notably with association findings at DAOA(G72), DISC1, and NRG1. Future identification of psychosis susceptibility genes will have a major impact on our understanding of disease pathophysiology and will lead to changes in classification and the clinical practice of psychiatry.
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PMID:The genetics of schizophrenia and bipolar disorder: dissecting psychosis. 1574 31

Genetic epidemiological studies suggest that individual variation in susceptibility to schizophrenia is largely genetic, reflecting alleles of moderate to small effect in multiple genes. Molecular genetic studies have identified several potential regions of linkage and two associated chromosomal abnormalities, and evidence is accumulating in favour of several positional candidate genes. Currently, the positional candidate genes for which we consider the evidence to be strong are those encoding dysbindin (DTNBP1) and neuregulin 1 (NRG1). For other genes, disrupted in schizophrenia 1 (DISC1), D-amino-acid oxidase (DAO), D-amino-acid oxidase activator (DAOA, formerly known as G72) and regulator of G-protein signalling 4 (RGS4), the data are promising but not yet compelling. The identification of these, and other susceptibility genes, will open up new avenues for research aimed at understanding the pathogenesis of schizophrenia, and will catalyse a re-appraisal of the classification of psychiatric disorders.
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PMID:Schizophrenia: genes at last? 1600 49

It has been conventional for psychiatric research, including the search for predisposing genes, to proceed under the assumption that schizophrenia and bipolar disorder are separate disease entities with different underlying etiologies. These represent Emil Kraepelin's traditional dichotomous classification of the so-called "functional" psychoses and form the basis of modern diagnostic practice. However, findings emerging from many fields of psychiatric research do not fit well with this model. In particular, the pattern of findings emerging from genetic studies shows increasing evidence for an overlap in genetic susceptibility across the traditional classification categories-including association findings at DAOA(G72), DTNBP1 (dysbindin), COMT, BDNF, DISC1, and NRG1. The emerging evidence suggests the possibility of relatively specific relationships between genotype and psychopathology. For example, DISC1 and NRG1 may confer susceptibility to a form of illness with mixed features of schizophrenia and mania. The elucidation of genotype-phenotype relationships is at an early stage, but current findings highlight the need to consider alternative approaches to classification and conceptualization for psychiatric research rather than continuing to rely heavily on the traditional Kraepelinian dichotomy. As psychosis susceptibility genes are identified and characterized over the next few years, this will have a major impact on our understanding of disease pathophysiology and will lead to changes in classification and the clinical practice of psychiatry.
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PMID:Genes for schizophrenia and bipolar disorder? Implications for psychiatric nosology. 1631 75

A recently discovered gene complex, G72/G30 (hereafter G72, but now termed DAOA), was found to be associated with schizophrenia and with bipolar disorder, possibly because of an indirect effect on NMDA neurotransmission. In principle, if G72 increases risk for psychosis by this mechanism, it might impact with greater penetrance those cortically based cognitive and neurophysiological functions associated with NMDA signaling. We performed two independent family-based association studies (one sample contained more than 200 families and the other more than 65) of multiple SNPs in the G72 region and of multiple SNPs in the gene for D-amino acid oxidase (DAAO), which may be modulated by G72. We examined the relationship between select cognitive measures in attention, working memory, and episodic memory and a restricted set of G72 SNPs in over 600 normal controls, schizophrenic patients, and their nonpsychotic siblings using mixed model ANOVAs. We also determined genotype effects on neurophysiology measures in normal controls using the fMRI BOLD response obtained during activation procedures involving either episodic memory or working memory. There were no significant single G72 SNP associations and clinical diagnosis in either sample, though one approached significance (p=0.06). Diagnosis by genotype interaction effects for G72 SNP 10 were significant for cognitive variables assessing working memory and attention (p=0.05), and at the trend level for episodic memory, such that in the schizophrenia group an exaggerated allele load effect in the predicted directions was observed. In the fMRI paradigms, a strong effect of G72 SNP 10 genotype was observed on BOLD activation in the hippocampus during the episodic memory paradigm. Tests of association with DAAO were consistently nonsignificant. We present evidence that SNP variations in the G72 gene region increase risk of cognitive impairment in schizophrenia. SNP variations were not strongly associated with clinical diagnosis in family-based analyses.
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PMID:The G72/G30 gene complex and cognitive abnormalities in schizophrenia. 1655 47

Though Kraepelin's century-old division of major mental illness into mood disorder and schizophrenia remains in place, debate abounds over the most appropriate classification. Although these arguments previously rested solely on clinical grounds, they now are rooted in genetics and neurobiology. This article reviews evidence from the fields of genetic epidemiology, linkage, association, cytogenetics, and gene expression. Taken together, these data suggest some overlap in the genes that predispose to bipolar disorder and schizophrenia. One gene, DAOA (D-amino acid oxidase activator, also known as G72), has been repeatedly implicated as an overlap gene, while DISC1 and others may constitute additional shared susceptibility genes. Further, some evidence implicates syndromes of co-occurring mood and psychotic symptoms in association with the putative risk alleles in overlap genes. From a nosologic perspective, the existence of overlap genes, coupled with the genotype-phenotype correlations discovered to date, supports the reality of the much debated schizoaffective disorder. Potential non-overlap syndromes--such as nonpsychotic bipolar disorder or cyclothymic temperament, on the one hand, and negative symptoms or the deficit syndrome, on the other--could turn out to have their own unique genetic determinants. If genotypes are to be the anchor points of a clinically useful system of classification, they must ultimately be shown to inform prognosis, treatment, and prevention. No gene variants have yet met these tests in bipolar disorder or schizophrenia.
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PMID:Carving chaos: genetics and the classification of mood and psychotic syndromes. 1660 72

The enormous public health importance of mood disorders, when considered alongside their substantial heritabilities, has stimulated much work, predominantly in bipolar disorder but increasingly in unipolar depression, aimed at identifying susceptibility genes using both positional and functional molecular genetic approaches. Several regions of interest have emerged in linkage studies and, recently, evidence implicating specific genes has been reported; the best supported include BDNF and DAOA but further replications are required and phenotypic relationships and biological mechanisms need investigation. The complexity of psychiatric phenotypes is demonstrated by (a) the evidence accumulating for an overlap in genetic susceptibility across the traditional classification systems that divide disorders into schizophrenia and mood disorders, and (b) evidence suggestive of gene-environment interactions.
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PMID:Genetics of affective (mood) disorders. 1672 2

The genes of D-amino acid oxidase (DAAO) activator (DAOA or G72; 13q34) and DAAO (12q24) have been suggested as candidate genes and involved in the N-methyl-D-aspartate receptor regulation pathway for schizophrenia. In order to evaluate the potential association of these two genes with schizophrenia in a Taiwanese sample, three single nucleotide polymorphisms (SNPs) for DAAO (rs2111902, rs3918346, rs3741775) and eleven SNPs for G72 (rs3916965, rs3916966, rs3916967, rs2391191, rs3916968, rs947267, rs778294, rs3916970, rs3916971, rs778293, rs3918342) were genotyped by the MALDI-TOF mass spectrometry method in 218 families (864 individuals) containing at least two siblings affected with schizophrenia. In SNP-based single locus association analyses, neither G72 nor DAAO showed significant association with schizophrenia. Additionally, a three-SNP haplotype in DAAO, and a four-SNP as well as a two-SNP haplotype in G72, showed no significant associations with schizophrenia. These results suggest that the DAAO and G72 genes are not susceptibility genes for schizophrenia in a Taiwanese sample.
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PMID:No association of G72 and D-amino acid oxidase genes with schizophrenia. 1684 73

With its hallucinations, delusions, thought disorder, and cognitive deficits, schizophrenia affects the most basic human processes of perception, emotion, and judgment. Evidence increasingly suggests that schizophrenia is a subtle disorder of brain development and plasticity. Genetic studies are beginning to identify proteins of candidate genetic risk factors for schizophrenia, including dysbindin, neuregulin 1, DAOA, COMT, and DISC1, and neurobiological studies of the normal and variant forms of these genes are now well justified. We suggest that DISC1 may offer especially valuable insights. Mechanistic studies of the properties of these candidate genes and their protein products should clarify the molecular, cellular, and systems-level pathogenesis of schizophrenia. This can help redefine the schizophrenia phenotype and shed light on the relationship between schizophrenia and other major psychiatric disorders. Understanding these basic pathologic processes may yield novel targets for the development of more effective treatments.
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PMID:Neurobiology of schizophrenia. 1701 32

Causal treatment options for schizophrenia are lacking due to our restricted knowledge of its etiology and pathogenesis. However, recently three postulated disposition genes for schizophrenia have been increasingly better confirmed: dysbindin, neuregulin-1, and G(72)/DAOA genes. These genes code proteins involved in processes ranging from brain development to the maintenance of glutamatergic transmission in the mature brain. Current interpretation of neuroanatomical findings points at reminiscences of disturbed brain development and a loss of nonneuronal elements, the so-called neuropil, as a correlate of brain atrophy. This reduction in neuropil is mainly caused by synaptic elements. Biochemical findings supporting this show that besides the dopaminergic and serotonergic system, glutamatergic transmission is also disturbed in schizophrenia. All these findings fit very well with the presumed functions of the disposition genes. Hypothesis-free approaches in structural brain imaging and the combination of functional imaging with relevant gene variants open new avenues for using markers from brain imaging to improve the diagnosis of schizophrenia and judge the response to neuroleptic treatment. Despite the enormous increase in knowledge for example in genetic research, the risk variants known until now provide no contribution to early diagnosis of schizophrenia. Furthermore, pharmacogenetics is currently unable to give a clear answer as to whether a single patient is responding to treatment or not.
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PMID:[Advances in neurobiological understanding of schizophrenia. Perspectives for new therapeutic concepts]. 1707 67


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