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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dopamine receptors are classified into D1 and D2 subtypes on the basis of their pharmacological properties and the intracellular responses they mediate. The cerebral D2 dopamine receptor is the target of drugs used to alleviate the main symptoms of schizophrenia. Although it is considered to be a single molecular entity, there is evidence that multiple D2-receptor subtypes exist. A complementary DNA encoding a D2 receptor has recently been cloned and the deduced 415-amino-acid sequence indicates that it belongs to the large superfamily of receptors coupled to G proteins, and that its topology consists of seven transmembrane domains. In this family, the genes are frequently without introns and each is believed to encode a unique polypeptide product. Here we show that the gene for the D2 receptor produces two receptor isoforms by alternative messenger RNA splicing, providing a route to receptor diversity in this family. One isoform corresponds to the D2(415) receptor, but the second contains an additional sequence encoding a 29-amino-acid fragment, defining a novel D2(444) receptor isoform. Expression of the two isoforms is tissue-specific, and both are regulated by guanyl nucleotides. As the extra sequence is located within a putative cytoplasmic loop that binds to G proteins, the two isoforms might interact with different G proteins and thereby initiate distinct intracellular signals.
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PMID:Alternative splicing directs the expression of two D2 dopamine receptor isoforms. 253 47

Despite many years of research, the genetic factors in schizophrenia are not well understood. Recent developments in DNA technology allow new methods of testing genetic hypotheses in the etiology of this debilitating disorder. We have found evidence against linkage of schizophrenia in a Swedish kindred to markers on chromosome 5; another research group has reported positive evidence for linkage to this same chromosomal region in British and Icelandic families. This article presents a set of data expanded from our previous report, discusses the issue of heterogeneity, and reviews the current status of linkage studies in schizophrenia.
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PMID:Molecular genetic studies in schizophrenia. 257 49

Significant advances in linkage studies have occurred the past decade based on the use of polymorphic DNA markers known as restriction fragment length polymorphisms (RFLPs). This approach has led to the chromosomal localization of a number of important genetic diseases, and is being increasingly applied to schizophrenia. We discuss two strategies for performing linkage studies in schizophrenia, one based on methodical testing of the human genome, and the other based on selective use of markers. The selective approach uses data from the mode of transmission, previous linkage studies, cytogenetic studies, association studies, case reports, and candidate genes to identify markers that may have an increased likelihood for linkage.
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PMID:Strategies for linkage studies in schizophrenia. 257 74

Clinical chemistry is going through an identity crisis, squeezed between automation (de-skilling) on the service side and molecular genetics in research. Automated routine estimations are now carried out and interpreted by machines; the skilled staff members required are more likely to have degrees in electronics than medicine or biochemistry. The role of molecular genetics is more ambiguous; it is inherently reductionist, in that it attempts to explain most clinical phenomena in terms of DNA sequence alone. This has been remarkably successful for single-gene defects (such as those causing Duchenne muscular dystrophy, hemoglobinopathies, cystic fibrosis, and ataxias) and may well prove equally so for Alzheimer's disease, cancer, heart disease, and schizophrenia. DNA diagnosis is not yet routine, but because of technical advances such as gene amplification ("PCR") and high-sensitivity gene-detection assays, it may soon become so, not only in major centers but also in local pathology laboratories and general practice. Clinical chemists must decide whether they wish to respond to this new and stimulating challenge by retooling and retraining. Should anyone be permitted into clinical chemistry during the 1990s without knowledge of both electronics and molecular genetics? Will there be a clinical chemistry in the twenty-first century other than through molecular genetics? This article is a personal response to these questions.
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PMID:Molecular genetics and the transformation of clinical chemistry. 233 3

Two independent lines of evidence support the localization of a schizophrenia susceptibility locus to the proximal long arm of chromosome 5. A partial trisomy of chromosome 5 (5q11.2-q13.3) cosegregates with the disorder in a Canadian family of Chinese descent, and DNA markers from proximal 5q cosegregate with schizophrenia (plus related disorders) in families of British and Icelandic descent. We constructed a human:hamster hybrid cell line (HHW 1064) whose only human complement is a chromosome 5 that is missing the trisomic region associated with schizophrenia. In combination with a "matched" cell hybrid (HHW 105) containing an intact chromosome 5, we physically mapped DNA markers relative to the trisomy. "Schizophrenia-linked" DNA markers p105-153Ra (D5S39) and p105-599Ha (D5S76) map within the trisomy and proximal to the 5q11.2 breakpoint, respectively. The hybrid cell lines HHW 105 and HHW 1064 together provide a means to identify and generate syntenic DNA markers to further investigate the location of a schizophrenia locus.
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PMID:Deletion mapping of DNA markers to a region of chromosome 5 that cosegregates with schizophrenia. 259 72

The difficulties anticipated in the application of molecular genetics to schizophrenia research have not prevented the first successful localization of a susceptibility gene for a subtype of schizophrenia. It is argued that this approach is the most useful of the possible molecular genetic strategies because it leads both to enhanced clinical genetic investigation and to further recombinant DNA research to clone and sequence schizophrenia susceptibility mutations. Future recombinant DNA research can now use long-range mapping and cloning techniques such as the chromosome walking/jumping approach and the strategy of cloning brain-specific cDNAs from brain mRNA. The identification of carriers for high-risk studies and the genetic validation of diagnosis appear to be the most promising clinical developments. Prenatal counseling will only become widely feasible when much more is known about the extent of heterogeneity of linkage in schizophrenia.
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PMID:Recent and future molecular genetic research into schizophrenia. 268 38

A current overview of the genetics of schizophrenia is presented. Recently reported linkage studies of schizophrenia using polymorphic DNA markers are discussed and critically evaluated. Linkage studies of schizophrenia that we are currently undertaking are described, and the rationale underlying the specific strategies that we are using is explained. Our major focus is on extended pedigrees ascertained in Ireland containing a high density of schizophrenic cases, but we are also planning to use the technique of homozygosity mapping in an attempt to localize a recessively inherited gene that may be segregating in consanguineous families ascertained in Saudi Arabia. Issues relating to diagnostic criteria, the choice of which DNA markers to type with the highest priority, and appropriate statistical methodology are also considered.
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PMID:Strategies for linkage studies of schizophrenia: pedigrees, DNA markers, and statistical analyses. 268 39

Two recent studies have suggested that a schizophrenia susceptibility locus may lie on the proximal long arm of chromosome 5. Partial trisomy of a 20-30 centimorgan region of chromosome 5 (5q11.2-13.3) was found to cosegregate with schizophrenia in a Canadian family of Chinese descent. Moreover, DNA markers from proximal 5q (D5S39, D5S76) were found to be linked to schizophrenia and related disorders in seven British and Icelandic families. We now report an initial physical map of DNA markers relative to the partial trisomy chromosome 5, as well as preliminary evidence against linkage of this region to schizophrenia in four American families.
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PMID:Physical mapping, linkage analysis of a putative schizophrenia locus on chromosome 5q. 281 74

Using highly sensitive nucleic acids hybridization techniques, which allow the detection of 0.1-0.5 single copy gene equivalents per cell, DNA from the temporal cortex of seven definite schizophrenics, five persons with schizophrenia-like psychoses, three patients with Huntington's chorea and nine mentally normal individuals were probed with human cytomegalovirus (HCMV) DNA. A clear hybridization signal was obtained with DNA from the temporal lobe of a young schizophrenic patient, whereas DNA from the temporal cortex of controls did not hybridize to the HCMV probe. This finding is in agreement with the cytomegalovirus hypothesis of schizophrenia and hints at the possibility that viral infection of the temporal cortex may in some sporadic cases be a contributing factor to the development of schizophrenic psychoses. There is no indication, however, that infection of the central nervous system with HCMV is an aetiological factor in the great majority of schizophrenic disorders. Clearly further studies, preferably in situ hybridizations of whole brains, are needed to prove or disprove the cytomegalovirus hypothesis of schizophrenia.
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PMID:Human cytomegalovirus DNA in the temporal cortex of a schizophrenic patient. 285 Jan 88

Schizophrenia is a common disorder with a life time prevalence of approximately 1 per cent. The illness often develops in young adults, who were previously normal, and is characterized by a constellation of symptoms including hallucinations and delusions (psychotic symptoms) and symptoms such as severely inappropriate emotional responses, a disorder of thinking and concentration, erratic behaviour as well as social and occupational deterioration. A considerable proportion of the variance in the liability to develop schizophrenia may be genetic, but segregation analysis, to establish a mode of transmission, has not produced a consistent result. One of these studies was carried out in Iceland and made use of the large family size and extensive geneaological information present in that country. Here we demonstrate genetic linkage of two DNA polymorphisms on the long arm of human chromosome 5 to schizophrenia in seven British and Icelandic families with multiple affected members. The results indicate the existence of a gene locus with a dominant schizophrenia-susceptibility allele. Inheritance of the allele in the families studied suggests that it may also predispose to psychiatric conditions such as schizophrenia spectrum disorders and a variety of other disorders. This report provides the first strong evidence for the involvement of a single gene in the causation of schizophrenia.
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PMID:Localization of a susceptibility locus for schizophrenia on chromosome 5. 290 49


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