Impact of NHS Direct on demand for immediate care. NHS Direct must be better marketed and deal with problems more effectively.
Explore the source record for details and available documents.
Emergency Service, Hospital↗
Biomedical subjects
E Parfitt
Publications and source records attributed to E Parfitt.
Autosome search for schizophrenia susceptibility genes in multiply affected families.
We have analysed 298 polymorphic markers in 13 families multiply affected with schizophrenia and related disorders using a combination of radiolabelled and fluorescent-based methodologies. The markers were distributed throughout the autosomes at an average spacing of 12.8 cM. The data were analysed with two-point linkage analysis (MLINK) and heterogeneity testing (HOMOG). Several genetic models were used ranging from near dominant to fully recessive. Multi-point analysis was performed for 27 regions demonstrating either contiguously positive lod scores in two or more consecutive markers, and in regions with two-point lod score(s) of 1.0 or above in a single marker. A proportion of the multi-point regions have been implicated in previous studies, thereby decreasing risk of false-positive results. However neither our two-point, nor multi-point scores reached the threshold value for significance of 3. 6. Nevertheless three regions were suggestive of linkage.
Chromosome Mapping↗
Linkage studies of bipolar disorder in the region of the Darier's disease gene on chromosome 12q23-24.1.
We have recently described a family in which there is cosegregation of major affective disorder with Darier's disease and have mapped this autosomal dominant skin disorder to 12q23-q24.1. This has provided an interesting candidate region for genetic studies of bipolar disorder. We have studied the segregation of seven markers spanning the Darier's disease locus in 45 bipolar disorder pedigrees and found modest evidence in support of linkage under heterogeneity for 5 of these markers. Nonparametric analyses were suggestive of linkage with a marker at the gene encoding a secretory form of phospholipase A2. Our sample has relatively low power to detect linkage under heterogeneity and independent researchers should examine markers from this region in further samples of bipolar pedigrees.
Alleles↗
Relationship between homozygosity at the dopamine D3 receptor gene and schizophrenia.
We have reported an association between schizophrenia and homozygosity of a Bal I polymorphism in the first exon of the dopamine D3 receptor gene (Crocq et al.: Journal of Medical Genetics 29:858-860, 1992). The present study consists of an attempt to replicate this finding in a further sample of 66 patients and 97 controls. Once again more patients than controls were homozygous, but the effect was not as strong as in our first study (chi 2 = 2.53, P = 0.05, one tailed). When pooled data from our two studies were analysed, excess homozygosity in patients remained highly significant (P = 0.002) with a particular excess of the 1:1 genotype (P = 0.01). This reflected a departure from Hardy-Weinberg equilibrium in the patients (P = 0.0005) but not the controls (P = 0.24). This led us to explore the possibility that there might be important differences between the patients in our two studies and that excess homozygosity might be a characteristic of particular subgroups of schizophrenics. Our findings suggest that the effect is consistently at its strongest in those patients who have a high familial loading and in those who have a good response to neuroleptic treatment, and that differences between our two samples might have contributed to the quantitatively different outcomes.
Adult↗
The gene for Darier's disease maps between D12S78 and D12S79.
Darier's disease is a dominantly inherited skin disorder in which there is abnormal adhesion between keratinocytes. We and others have recently mapped the disease gene to chromosome 12q23-q 24.1. In the present study we have established that the disease gene lies between the loci D12S78 and D12S79 which are 12cM apart. We have also obtained direct evidence that the disease is unlikely to result from a mutation in one of the members of the keratin gene cluster on chromosome 12q.
Chromosome Mapping↗
Polymorphisms in the keratin 8 gene detected by PCR.
Explore the source record for details and available documents.
Base Sequence↗
Bipolar affective puerperal psychosis associated with consanguinity.
Most clinical and genetic evidence suggests that puerperal psychosis is closely related to bipolar affective disorder. During a linkage study of bipolar disorder we ascertained a British family in which puerperal psychosis was associated with consanguinity in three sisters. All three subjects had lifetime RDC diagnoses of bipolar I or manic disorder. An inbred brother also had bipolar I disorder. The only female member of the sibship to escape puerperal psychosis was outbred. These findings are consistent with several genetic models for bipolar disorder in this family. The most interesting possibility is a single major susceptibility locus of recessive effect. Under this assumption, the family could be used for homozygosity mapping to help localise the putative recessive locus. If other inbred families can be found in which the same putative recessive locus is operating, the power to localise the gene by homozygosity mapping would be greatly increased.
Bipolar Disorder↗
A linkage study of schizophrenia with DNA markers from the long arm of chromosome 11.
We report the results of a collaborative linkage study using 12 polymorphic markers (9 loci) from the long arm of chromosome 11, and 24 families multiply affected with schizophrenia and other closely related disorders. This region is of interest because several families have been reported in which balanced translocations involving 11q apparently co-segregate with psychotic illness. In addition, the dopamine D2 receptor, porphobilinogen deaminase, and tyrosinase genes map within the region studied and may be aetiologically involved in schizophrenia. We have primarily analysed genotypic data by the LOD score method using a range of single gene models. In order to minimize error due to mis-specification of genetic parameters we have analysed data from markers at candidate gene loci by the non-parametric extended sib-pair method in addition to the LOD score method. Our results suggest that most of the region can be excluded from containing a gene of major effect in the aetiology of this disease.
Alleles↗
No evidence for a pseudoautosomal locus for schizophrenia. Linkage analysis of multiply affected families.
Evidence for a pseudoautosomal locus for a schizophrenia susceptibility gene was sought by two forms of analysis of 25 multiply affected families. Firstly, in the sample as a whole there was an excess of same-sex over mixed-sex siblings compared with that expected. Secondly, linkage analysis was performed in six of the families. The genotypes were studied for DXYS14, a highly polymorphic marker in the telomeric pseudoautosomal region. No evidence for positive linkage was found with two-point analysis under eight different genetic models for the mode of transmission. A non-parametric, sibling-pair analysis also failed to detect linkage. Our findings provide no evidence for linkage within the pseudoautosomal region; same-sex concordance must arise from some other mechanism.
Blotting, Southern↗
Mononucleotide repeat polymorphism in the APP gene.
Explore the source record for details and available documents.
Alleles↗
No association between RFLPs at the porphobilinogen deaminase gene and schizophrenia.
An association study of restriction fragment length polymorphisms (RFLPs) in the porphobilinogen deaminase (PBGD) gene and schizophrenia was conducted. RFLPs detected by MspI, PstI, ApaLI and BstNI in intron 1 of the gene were studied in 49 patients and 79 controls. There were no significant differences between the groups in allele frequencies, genotype counts or haplotype distribution.
Adult↗
No evidence for linkage between schizophrenia and eight microsatellite markers on chromosome 19.
We report the results of a linkage study of eight markers on chromosome 19 in a sample of 24 families multiply affected with schizophrenia and related psychoses. This study forms part of a systematic search of the entire genome using microsatellite markers spaced at 10-20 cM intervals. These data provide no evidence for the presence of a gene of major effect on chromosome 19 under the assumption of genetic homogeneity or heterogeneity. We have attempted to describe the extent to which this region has been excluded and demonstrate that while it is possible to exclude near-dominant and recessive models under the assumption that all families are linked to the same locus, power for exclusion falls away rapidly when incomplete penetrance and heterogeneity are invoked.
Chromosomes, Human, Pair 19↗