ISSN:0955-8829    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Chromosome 12q23-q24.1 has been implied by a few linkage and association studies as a candidate region for affective disorder. The present study investigated for linkage between bipolar affective disorder and 16 microsatellite markers covering chromosome 12q22-q24 in two Danish families.Assuming homogeneity and a dominant mode of inheritance, a significant two-point lod score of 3.37 was found at D12S1639, when only bipolar patients were considered as affected. The lod score was supported by neighbouring markers. The empiricalP-value for this lod score was 0.00002. Non-parametric analyses using SimIBD supported this finding, withP-values of 0.00003 and 0.005 at D12S1639. An overlapping segment of chromosome 12q24 was shared among all except one of the bipolar patients, with apparently different haplotypes in each family.

ISSN:0955-8829    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

In the sense of a paradigm for the heritability of complex psychiatric disorders, we compared the brain wave patterns of a 12-sib family with those of 144 unrelated controls and with those of 14 pairs of monozygotic twins. Under constant experimental conditions, electroencephalogram (EEG) parameters generally displayed a broad range of inter-individual differences, but were also remarkably stable over time within each subject, thus suggesting that the variation of EEG parameters forms a continuous phenotypic range rather than discrete phenotype classes. The distributions of all EEG parameters were found to be unimodal but significantly different from a normal distribution. Although an unimodal distribution speaks in favor of a polygenic additive mode of inheritance, this may not necessarily be true. Our findings might reflect the fact that a symmetric environmental distribution is converted through the underlying genotypes' norm of reaction into an asymmetric phenotype distribution. On the other hand, the distributions of the power-related EEG parameters were not that clearly unimodal, and with a larger sample size a trimodal solution might have become significant.With respect to the between-sib EEG similarity, we found the empirically derived value to be approximately half that of the within-subject similarity at 14-day intervals and of the within-pair similarity of monozygotic twins. This finding confirmed earlier results on monozygotic twins brought up together and reared apart, concerning the estimated value ofh2. All in all, the EEG paradigm has clearly demonstrated that the methods of quantitative genetics represent a powerful tool once phenotypes designed to assess the variation of a trait are based on dimensional quantities.

ISSN:0955-8829    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Several recent reports have provided evidence suggesting linkage of markers on chromosome 13q14.1-q32 to schizophrenia in families from England, Wales, Japan and the USA, but not in Chinese families. We tested for linkage between markers in this region and schizophrenia in a sample of 16 families multiply affected with schizophrenia drawn from the Bantu-speaking black population of South Africa. Twelve markers spanning 76 cM of chromosome 13q were examined in these analyses, including 10 markers covering the most positive region in the studies of the English, Welsh and Chinese families, and two additional markers yielding the largest positive LOD scores in the American study. The map of markers used was D13S126–14.6cM-D13S119–12.2cM-D13S144–10.2cM-D13S160–7.9cM-D13S121–6.3cM-D13S71–1.6cM-D13S122–4.9cM-D13S128–8.9cM-D13S770–1.4cM-D13S779–2.2cM-D13S64–7.4cM-D13S173. Parametric two-point analysis yields strongly negative LOD scores across the region D13S71-D13S64 under all models, and D13S71-D13S173 under a recessive model, when analysing either the whole sample or affected individuals only. ALOD maxima are 0.0 when allowing for heterogeneity for all markers in this subset. Under recessive modelling, the ALOD maximum is 0.717, Θ = 0.0, α = 0.45, for D13S126 when analysing all samples. Affected-only analysis of this marker yields a maximum, LOD score of 0.645, Θ = 0.1, and an ALOD maximum of 0.697, Θ = 0.0, α = 0.55.Non-parametric multipoint analysis of these markers provides no support for excess sharing of alleles identical by descent, although D13S119 and D13S770 show some evidence for excess sharing of alleles identical by state.

ISSN:0955-8829    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Evidence from anatomical, pharmacological, and animal studies on the involvement of the dopamine system in obsessive-compulsive disorder (OCD) is mounting. This, along with evidence for a genetic diathesis provided by family and twin studies, prompted us to conduct genetic association studies of dopamine system genes in OCD. We genotyped OCD patients (n> 100) and matched controls for four loci: (1) a 40-base-pair repeat in the dopamine transporter gene; (2) the Taq1A polymorphism and the serine/cysteine variation in the D2 dopamine receptor gene; (3) an MscI polymorphism in the D3 dopamine receptor gene; and (4) a 48-base-pair repeat in the D4 dopamine receptor gene. Significant differences in allele frequencies were found between patients and controls for the D4 receptor gene, although replication is required with family-based controls before any conclusions can be entertained. This study represents the first comprehensive assessment of the roles of dopamine system genes in OCD.

ISSN:0955-8829    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Eight multiplex Utah schizophrenia pedigrees were screened for linkage by applying a non-parametric linkage program, GENEHUNTER, using 30 chromosome 6 DNA markers. The overall maximum NPL score of the combined pedigrees was 1.50 (P= 0.079) at marker D6s281, located near the q terminus. The highest overall maximum NPL score for an individual pedigree was 2.81 (P= 0.043). In the chromosome 6p region, where numerous positive findings have been reported, we obtained no positive results.

ISSN:0955-8829    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

A balanced t(1;11)(q42.1;q14.3) translocation segregates with schizophrenia and related mental illness in a single large Scottish pedigree. We have constructed a long-range restriction map covering at least 3 Mb of the chromosome 11 breakpoint region and conducted searches for genes whose expression could be altered by the translocation, resulting in schizophrenia. Novel transcribed sequences of unknown function clustered around putative CpG islands, located approximately 500 kb and 700 kb above the breakpoint, represent the only evidence to date for expressed genes within the mapped region.

ISSN:0955-8829    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Since 1969, several classical linkage studies suggested an X-chromosome locus for bipolar affective disorder. However, methods using highly polymorphic DNA markers have provided conflicting evidence for linkage, and an X-chromosomal locus for bipolar disorder remains controversial. More recently, Pekkarinenet al.(1995) found a maximum LOD score of 3.54 at the marker DXS994 in a large bipolar Finnish kindred. In the present study, we attempted to replicate this finding using 43 families multiply affected by bipolar affective disorder. These families were selected for the absence of male-to-male transmission of the disease, and were genotyped for two microsatellte markers, DXS1227 and DXS1062 (which is about 2 cM telomeric to DXS994). Linkage to this region was excluded either using a two-point lod score method with two plausible genetic models, or by a model-free lod score analysis which does not require specification of a particular mode of transmission. We conclude that there is no evidence of a common major gene for bipolar affective disorder at Xq25-q27 in our set of families.

ISSN:0955-8829    

出版商:OVID    

年代:1998

数据来源: OVID

ISSN:0955-8829    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

There is evidence of increased phospholipid breakdown in cell membranes of patients suffering from schizophrenia. This may be related to increased levels of the enzyme cytosolic phospholipase A2 (cPLA2) which have been reported in schizophrenic subjects. We have identified a Ban 1 dimorphic site on the first intron of the cPLA2 gene. Schizophrenic subjects were found to have a significant excess of the A2/A2 homozygote relative to healthy control subjects. Genetically determined alterations in phospholipase activity may thus underlie the reported abnormalities of phospholipid metabolism in schizophrenia.

ISSN:0955-8829    

出版商:OVID    

年代:1998

数据来源: OVID