Down's syndrome screening.
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Down Syndrome↗
Biomedical subjects
M Gill
Publications and source records attributed to M Gill.
Association between schizophrenia and T102C polymorphism of the 5-hydroxytryptamine type 2a-receptor gene. European Multicentre Association Study of Schizophrenia (EMASS) Group.
BACKGROUND: An association between schizophrenia and the T102C polymorphism of the gene for 5-hydroxytryptamine type 2a (5-HT2a) receptor has been reported; the proportion of allele 2 of this polymorphism is higher than expected among schizophrenic patients. We looked for an association between schizophrenia and this variant of the 5-HT2a-receptor gene in a large multicentre study. METHODS: Seven countries recruited 1210 participants: 571 white schizophrenic patients and 639 ethnically matched controls. All patients had a diagnosis of schizophrenia or schizoaffective disorder. High-molecular-weight DNA was isolated from lymphocytes. PCR amplification and restriction enzyme digestion was used to examine sequence variation of the 5-HT2a-receptor gene. Genotypes 1/1, 1/2, and 2/2 were assigned. Woolf's method was used to look for an association between schizophrenia and allele 2 and the 2/2 genotype. FINDINGS: We found a significant overall association between schizophrenia and allele 2 with an odds ratio of 1.3 (95% Cl 1.1-1.53, p = 0.003). No evidence for heterogeneity was observed between samples. We found a highly significant excess of the 1-2/2-2 genotypes in schizophrenia (p = 0.008) with a relative risk of 1.7 (1.22-2.36) and an attributable fraction of 0.35. INTERPRETATION: Our findings suggest that the gene for 5-HT2a-receptor, or a locus in linkage disequilibrium with it, confers susceptibility to schizophrenia. Allele 2 is common in the population and it is, therefore, likely that this variant, or a nearby polymorphism, may affect a significant proportion of schizophrenic patients.
Alleles↗
A combined analysis of D22S278 marker alleles in affected sib-pairs: support for a susceptibility locus for schizophrenia at chromosome 22q12. Schizophrenia Collaborative Linkage Group (Chromosome 22).
Several groups have reported weak evidence for linkage between schizophrenia and genetic markers located on chromosome 22q using the lod score method of analysis. However these findings involved different genetic markers and methods of analysis, and so were not directly comparable. To resolve this issue we have performed a combined analysis of genotypic data from the marker D22S278 in multiply affected schizophrenic families derived from 11 independent research groups worldwide. This marker was chosen because it showed maximum evidence for linkage in three independent datasets (Vallada et al., Am J Med Genet 60:139-146, 1995; Polymeropoulos et al., Neuropsychiatr Genet 54:93-99, 1994; Lasseter et al., Am J Med Genet, 60:172-173, 1995. Using the affected sib-pair method as implemented by the program ESPA, the combined dataset showed 252 alleles shared compared with 188 alleles not share (chi-square 9.31, 1df, P = 0.001) where parental genotype data was completely known. When sib-pairs for whom parental data was assigned according to probability were included the number of alleles shared was 514.1 compared with 437.8 not shared (chi-square 6.12, 1df, P = 0.006). Similar results were obtained when a likelihood ratio method for sib-pair analysis was used. These results indicate that may be a susceptibility locus for schizophrenia at 22q12.
Alleles↗
Recent advances in obstetrics. Figures on screening for Down's syndrome are inaccurate.
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Down Syndrome↗
Allelic association between a Ser-9-Gly polymorphism in the dopamine D3 receptor gene and schizophrenia.
We examined a Ser-9-Gly polymorphism in the dopamine D3 receptor gene for allelic association with schizophrenia in 133 patients currently treated with clozapine and 109 controls. Allele 1 (Ser-9) was significantly more frequent in the patients (69%) than in the controls (56%) (P = 0.004). The 1-1 genotype was more common (43% vs 30%) and the 2-2 genotype less common (5% vs 18%) in patients than in controls. When the patient group was subdivided on the basis of clinical response to clozapine, using a 20-point improvement in the global assessment scale as cut-off, genotype 1-1 was found to be more frequent among the non-responders (53% vs 36%, P = 0.04). To place our results in the context of previous studies of this polymorphism and schizophrenia, we performed a meta-analysis of all published data including the present sample. The combined analysis shows evidence for a modest association between genotype 1-1 and schizophrenia (odds ratio 1.25, 95% confidence interval 1.05-1.49, P = 0.01). These results suggest that the Ser-9 allele, or a nearby polymorphism in linkage disequilibrium, results in a small increase in susceptibility to schizophrenia.
Alleles↗
Assessing the statistical power to detect linkage in a sample of 51 bipolar affective disorder pedigrees.
We used computer simulation method to address the question of power in an initial collaborative sample of 51 bipolar affective disorder pedigrees. Simulations were performed for all possible combinations using (1) two levels of diagnostic stringency, (2) three transmission models, (3) locus heterogeneity, and (4) different assumed phenocopy rates. Some of the factors affect the power to detect linkage are (1) the specification of the correct genetic model, (2) the degree of locus heterogeneity, and (3) the frequency of phenocopies. The first two assertions were supported by our simulation results, but varying the rates of phenocopy did not substantially alter the power of the sample until a critical point. However, it is important to point out that these results are dependent on the genetic models under study and on the use of the "correct" model (i.e., the one used to simulate the data). If we assume a dominant mode of inheritance and locus homogeneity, the power to detect linkage is 97.5% at a theta of .01. However, the power declines dramatically, to 60.5% and 14.7%, if only 75 and 50% of the families are linked, respectively. Locus heterogeneity has a similar effect on the power of the sample to exclude linkage. The relative lack of power in our data, in the presence of significant locus heterogeneity, and for an intermediate mode of inheritance, underscores the need for multicenter collaboration.
Adolescent↗
Influence of soyabean meal supplementation on the resistance of Scottish blackface lambs to haemonchosis.
Protein supplementation improves the resistance of sheep to haemonchosis. This experiment investigated the Scottish blackface breed to establish whether dietary protein supplementation is still beneficial in a genetically resistant breed. Lambs were given either a basal diet or a diet supplemented with soyabean meal to give an additional 80 g crude protein kg dry matter-1. The lambs were given an initial loading dose of Haemonchus contortus, followed by a trickle infection for 10 weeks. The weight gains of the lambs given the supplemented diet were greater and their carcases were leaner, irrespective of infection status. Infected animals on the basal diet were more anaemic and hypoalbuminaemic than animals receiving the supplemented diet, although there were no statistically significant differences in mean worm burdens or faecal egg counts.
Analysis of Variance↗
Schizophrenia and the androgen receptor gene: report of a sibship showing co-segregation with Reifenstein syndrome but no evidence for linkage in 23 multiply affected families.
Crow et al. [1993: Am J Med Genet (Neuropsychiatr Genet) 48:159-160] have reported excess sharing of alleles by male sibling pairs with schizophrenia, at a triplet repeat marker within the androgen receptor gene, indicating that mutations at or near this gene may be a risk factor for males. In this report, we describe a pair of male siblings concordant for both schizophrenia and Reifenstein syndrome, which is caused by a mutation in this gene. This provides support for the hypothesis that the androgen receptor may contribute to liability to develop schizophrenia. Because of this, we have examined a collection of 23 pedigrees multiply affected by schizophrenia for linkage to the androgen receptor. We have found no evidence for linkage by both the LOD score and affected sibling-pair methods, under a range of genetic models with a broad and narrow definition of phenotype, and when families with male-to-male transmission are excluded. However, because of the small number of informative male-male pairs in our sample, we cannot confirm or refute the excess allele sharing for males reported by Crow.
Adolescent↗
No evidence for linkage between the X-chromosome marker DXS7 and schizophrenia.
DeLisi et al. (1994b) have examined the X and Y chromosomes for linkage to schizophrenia in 126 small families and report a small positive LOD score for the marker DXS7, adjacent to the MAO locus at Xp11.4-11.3. Because of this, we have examined the DXS7 for linkage to schizophrenia using 17 pedigrees in which male-to-male transmission of schizophrenia was absent. Alleles at DXS7 were genotyped using the PCR and LOD scores calculated using five models of inheritance, including classical dominant recessive and intermediate models. LOD scores were substantially negative for all models examined and analysis for linkage heterogeneity using the LOD2 method showed no significance. Analysis by the nonparametric affected sib-pair method likewise indicated no linkage. We conclude that DXS7 is not a major locus for schizophrenia in our collection of pedigrees.
Family↗
Evidence for a genetic association between alleles of monoamine oxidase A gene and bipolar affective disorder.
We present evidence of a genetic association between bipolar disorder and alleles at 3 monoamine oxidase A (MAOA) markers, but not with alleles of a monoamine oxidase B (MAOB) polymorphism. The 3 MAOA markers, including one associated with low MAOA activity, show strong allelic association with each other but surprisingly not with MAOB. Our results are significant only for females, though the number of males in our sample is too small to draw any definite conclusions. Our data is consistent with recent reports of reduced MAOA activity in patients with abnormal behavioral phenotypes. The strength of the association is weak, but significant, which suggests that alleles at the MAOA locus contribute to susceptibility to bipolar disorder rather than being a major determinant.
Alleles↗
Linkage studies on chromosome 22 in familial schizophrenia.
As part of a systematic search for a major genetic locus for schizophrenia we have examined chromosome 22 using 14 highly polymorphic markers in 23 disease pedigrees. The markers were distributed at an average distance of 6.6 cM, covering 70-80% of the chromosome. We analyzed the data by the lod score method using five plausible genetic models ranging from dominant to recessive, after testing the power of our sample under the same genetic parameters. The most positive lod score found was 1.51 under a recessive model for the marker D22S278, which is insufficient to conclude linkage. However, an excess of shared alleles in affected siblings (P < .01) was found for both D22S278 and D22S283. For D22S278, the A statistic was equal to the lod score (1.51) and therefore did not provide additional evidence for linkage allowing for heterogeneity, but the Liang statistic was more significant (P = .002). Our results suggest the possibility that the region around D22S278 and D22S283 contains a gene which contributes to the aetiology of schizophrenia.
Alleles↗
DNA stability and survival of Bacillus subtilis spores in extreme dryness.
The inactivation of Bacillus subtilis spores during long-term exposure (up to several months) to extreme dryness (especially vacuum) is strain-dependent, through only to a small degree. During a first phase (lasting about four days) monolayers of spores lose about 20% of their viability, regardless of the strain studied. During this phase loss in viability can be equally attributed both to damages of hydrophobic structures (membranes and proteins) and DNA. During a second phase lasting for the remaining time of experimental observation (weeks, months and years) the loss in viability is slowed. A viability of 55% to 75% (depending on the strain) is attained after a total exposure of 36 days. The loss in viability during the second phase can be correlated with the occurrence of DNA double strand breaks. Also covalent DNA-protein cross-links are formed by vacuum exposure. If the protein moiety of these cross-links is degraded by proteinase K-treatment in vitro additional DNA double strand breaks result. The data are also discussed with respect to survival on Mars and in near Earth orbits.
Bacillus subtilis↗
Influence of supplementation with dietary soyabean meal on resistance to haemonchosis in Hampshire down lambs.
The influence of dietary protein supplementation on resistance to haemonchosis was examined in Hampshire down lambs fed either a basal diet or a diet supplemented with soyabean. At seven months of age the lambs were challenged with an initial loading dose of Haemonchus contortus, followed by a trickle infection three times a week. Blood and faecal samples were collected three times a week and bodyweights were recorded weekly. After 10 weeks the lambs were slaughtered and their worm burdens and carcase composition determined. Although their mean worm burdens were similar, the lambs given the basal diet had higher faecal egg counts, lower packed red cell volumes and lower concentrations of total plasma protein and plasma albumin than the lambs given the supplemented diet. The dietary supplementation also improved the carcase composition of the lambs.
Animal Feed↗
Cytochrome P4502D6 genotype does not determine response to clozapine.
1. The atypical antipsychotic drug clozapine, used in the treatment of resistant schizophrenia, is metabolized partly by the hepatic cytochrome P450 enzyme CYP2D6. Two phenotypes with respect to the activity of the enzyme are recognized (extensive metabolisers (EM) and poor metabolisers (PM)), resulting from allelic variation in the gene, CYP2D6. 2. Genotype was determined in 123 schizophrenic patients currently being treated with clozapine, in order to determine if EM or PM status influences response to this drug. Patients were divided into responders and non-responders using the Global Assessment Scale, and genotyped for the A and B poor metaboliser mutations by digesting PCR products with HpaII or BstNI. 3. Fifty-nine patients were heterozygous for allele B and for allele A. Eight patients were determined as poor metabolisers since they were homozygous either for A and B. Poor metabolisers were equally distributed between responders and nonresponders and no correlation between CYP2D6 alleles and response to clozapine was found. 4. The results are consistent with recent findings showing that CYP1A2, rather than CYP2D6, is the major enzyme responsible for the metabolism of clozapine.
Alleles↗
No evidence of linkage or allelic association of schizophrenia with DNA markers at pericentric region of chromosome 9.
Based on our previous study suggesting the pericentric region of chromosome 9 as of potential importance in schizophrenia, we have carried out a linkage study between the schizophrenia phenotype and the dinucleotide repeat polymorphisms D9S55, D9S15, and D9S202 in three pedigrees multiply affected with schizophrenia. In addition, we have conducted allelic association studies using 60 patients with schizophrenia and 60 controls with polymorphisms at D9S55 and D9S15 markers. No evidence for linkage or association was found. The results indicate that susceptibility genes for schizophrenia are less likely to be located at the pericentric region of chromosome 9, assuming genetic homogeneity of the pedigrees.
Alleles↗
No evidence of association between dopamine D4 receptor variants and bipolar affective disorder.
Disturbance in the dopamine neurotransmitter system has been implicated in the pathogenesis of affective disorder. In this study, we examine the possibility that functional variants of the recently cloned dopamine D4 receptor gene contribute to the genetic component of manic depression. The polymorphism, a 48 bp tandem repeat coding for part of the third cytoplasmic loop, was detected using a PCR based method. In a first sample of 57 patients and 59 controls, we found allele 7 to be in excess in the patients. In contrast, allele 3 was less frequent in patients. A second, larger sample of 90 patients and 91 controls was utilized to test these hypotheses. Data from the two samples were then pooled together for further analyses. We calculated the power of our samples, and if the frequency of 7 repeat allele obtained from sample 1 is true, i.e., 25% (28/114) for patients and 14% (16/118) for controls, then the power of the combined sample is 62% at 5% (two-tailed) significance level. However, both observations were not replicated; we therefore conclude that variations in this repeat at the DRD4 gene do not contribute to the genetic component of manic depression.
Alleles↗
Community geriatricians. Elderly people need "high tech" services too.
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Aged↗
DRD2 Ser311/Cys311 polymorphism in schizophrenia.
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Cysteine↗