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M Owen

Publications and source records attributed to M Owen.

At least 73 records · Page 4Linked to original sources
PubMed1995

Chromosome 22 markers demonstrate transmission disequilibrium with schizophrenia.

Previously we reported evidence for genetic linkage between markers on chromosome 22q12 and schizophrenia in 23 multiply affected pedigrees. As part of further investigation of this region, we have applied the transmission disequilibrium test (TDT) to the genotype data. The TDT is a test for both linkage and linkage disequilibrium, and is based on the unequal probability of transmission of two different marker alleles from parents to affected offspring. We obtained significant results for the marker D22S283 (chi 2 = 35.9, 14 df, p = 0.001), D22S278 (chi 2 = 16.5, 6 df, p = 0.01) and F8VWFP (chi 2 = 13.1, 4 df, p = 0.01). Application of the Bonferonni correction for testing multiple markers renders the results for marker D22S278 and F8VWFP non-significant (from p = 0.01 to p = 0.14), while the result for D22S283 remains modestly significant at p < 0.02. Overall, our findings strengthen the suggestion that the region around D22S283 contains a susceptibility gene for schizophrenia.

Chromosome Mapping↗
PubMed1994

Variation at the fragile X locus does not influence susceptibility to bipolar disorder.

Over the last 20 years several pedigrees have been reported which are suggestive of linkage between susceptibility to bipolar disorder and markers on chromosome Xq28. Other workers have failed to replicate these reports and the methodology of the positive reports has been criticised. Recently there have been several reports of an association between fragile X (FRA(X)) and affective disorder within families and in unrelated individuals compared with controls. Such reports could be consistent with the Xq28 marker reports because FRA(X) maps to Xq27.3. We report a study at the FRA(X) CGG repeat locus in 79 unrelated Caucasian bipolar probands without fragile X syndrome and 77 unrelated controls. We found no evidence that variation at this locus confers susceptibility to bipolar disorder.

Adult↗
PubMed1994

Failure to find linkage between a functional polymorphism in the dopamine D4 receptor gene and schizophrenia.

We report the results of a linkage study in 24 families multiply affected with schizophrenia using a polymorphic DNA sequence encoding the third cytoplasmic loop of the dopamine D4 receptor. Two-point LOD score analyses with a range of single gene models ranging from near dominant to near recessive revealed no evidence for linkage. In addition, we examined the data by non-parametric sib-pair analysis and found no excess sharing of alleles between affected sib-pairs. We therefore conclude that mutations within the dopamine D4 receptor gene do not have a major aetiological role in schizophrenia in our collection of pedigrees.

Alleles↗
PubMed1994

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↗
PubMed1994

Association and haplotype analysis at the tyrosine hydroxylase locus in a combined German-British sample of manic depressive patients and controls.

Tyrosine hydroxylase (TH) is the key enzyme in the synthesis of catecholamines and may therefore be of aetiological relevance in the development of psychiatric illness. Hipolar affective disorder association studies, with restriction fragment length polymorphisms located in flanking regions of the TH gene, have shown conflicting results. Alleles of a tetranucleotide repeat polymorphism (TH4) located in intron 1 of the gene were tested for association with bipolar affective disorder in a combined German and British sample of 183 bipolar patients and 209 healthy control probands. No differences in TH4 allele frequencies were found in the two groups. A subset of patients and controls was typed with the flanking markers Ty7/BglII and pJ4.7/TaqI and frequencies of two-locus haplotypes were estimated. Linkage disequilibrium was found between TH4-Ty7 and TH4-pJ4.7. Haplotype frequencies did not differ between patients and controls.

Alleles↗
PubMed1994

Is there an inverse relationship between Down's syndrome and bipolar affective disorder? Literature review and genetic implications.

Several authors have suggested the existence of an inverse relationship between bipolar affective disorder and Down's syndrome (DS). The present authors have examined this hypothesis by a critical review of the literature. The present findings are consistent with a reduced rate of bipolar disorder in subjects with DS when compared with non-DS mentally retarded adults and with the general population. Thus, possession of an extra copy of chromosome 21 may confer protection against bipolar disorder. This could be the result of non-specific mechanisms or the action of a disease-modifying gene. However, the most interesting possibility is that either dominant or recessive alleles act at a major susceptibility locus for bipolar disorder on chromosome 21. Testable predictions result from the major susceptibility locus models. In order to investigate these hypotheses further, the present authors suggest the following: (1) further studies of the prevalence of bipolar disorder in DS; and (2) the reporting of all cases of bipolar disorder in trisomy 21 with details of the meiotic origin of the non-disjunction and details about affective disorder in relatives of the proband.

Alleles↗
PubMed1994

Confirmation of association between the e4 allele of apolipoprotein E and Alzheimer's disease.

The Apo E genotype of 86 patients with Alzheimer's disease (AD) and 77 age matched controls was determined by digestion of Apo E PCR products with the restriction enzyme CfoI. The frequency of the e4 allele was significantly increased in the patient group (0.33) as compared with controls (0.12). This effect was seen in patients with a family history and in sporadic cases. The odds ratio in homozygotes for the e4 allele was 11.24 (95% confidence interval 2.45-51.50). There was no relationship between age of onset and Apo E genotype. There was no linkage disequilibrium between the apolipoprotein E locus and a TaqI polymorphism at the Apo CII locus, and no allelic association between Apo CII and AD.

Age of Onset↗
PubMed1994

Familial cosegregation of major affective disorder and Darier's disease (keratosis follicularis)

Darier's disease is a rare autosomal dominantly inherited keratosis. This is an account of one family in which there is co-occurrence of major affective disorder and Darier's disease in five members and absence of both disorders in five members. The pedigree is consistent with genetic linkage between the Darier gene and a major autosomal dominant susceptibility locus for major affective disorder. When the Darier's disease gene has been mapped, its chromosomal location will be an interesting candidate locus for linkage studies of major affective disorder.

Adolescent↗
PubMed1994

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↗
PubMed1994

Chromosomal aberrations and bipolar affective disorder.

Chromosomal abnormalities associated with bipolar disorder may help in the localisation of susceptibility genes for bipolar illness by pinpointing 'candidate' regions of the genome for further study using molecular genetic methods. We review descriptions of chromosomal abnormalities in association with bipolar and related affective disorders and evaluate their relevance for localising susceptibility genes for bipolar disorder, using standardised criteria. We found 28 reports. We identified four genomic regions of potential interest: 11q21-25; 15q11-13; chromosome 21;Xq28. It is important that clinicians are able to recognise patients who may have chromosome abnormalities which could help in the localisation of susceptibility genes for psychiatric disorders. We suggest referral for specialist investigation and karyotyping, to a psychiatric genetics research group, of any patient with functional psychosis and one or more of the following: (a) a strong family history of functional psychosis; (b) mental retardation; (c) another disease known to be caused by a single gene; or (d) congenital abnormalities.

Bipolar Disorder↗
PubMed1994

The strength of the genetic effect. Is there room for an environmental influence in the aetiology of schizophrenia?

The evidence for a genetic contribution to schizophrenia is compelling. However, the pattern of inheritance is complex and it is usually assumed that environmental factors also have a role that will eventually be identified. We argue that this is not necessarily the case. While a hypothesis combining genetic diathesis with environmental stress cannot be disproved, it is also possible that 'non-genetic' factors consist entirely of stochastic events affecting gene expression or structure.

Diseases in Twins↗