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Biomedical subjects

G Thomson

Publications and source records attributed to G Thomson.

At least 145 records · Page 8Linked to original sources
PubMed1984

The genotypic distribution among non-insulin-dependent diabetes mellitus (NIDDM) patients of a restriction fragment length polymorphism.

The genotypic distribution among patients of a marker allele, or restriction fragment length polymorphism (RFLP), can be used to determine the mode of inheritance of a disease-predisposing gene, if the association of the marker with the disease is sufficiently high. In the case of noninsulin-dependent diabetes mellitus (NIDDM), the RFLP in the 5'-flanking region of the human insulin gene does not allow discrimination between dominant and recessive modes of inheritance, or between any intermediate model. Also, it is demonstrated, in general, that the observation of a higher odds ratio for individuals with two copies of a marker allele than for individuals with at least one copy does not in itself imply a gene-dosage model.

DNA Restriction Enzymes↗
PubMed1984

HLA DR antigens and susceptibility to insulin-dependent diabetes mellitus.

Two novel analytic methods to evaluate the roles of the HLA alleles of the human major histocompatibility complex in disease predisposition have been formulated and applied to insulin-dependent diabetes mellitus (IDDM). The HLA-DR antigens, as they are presently defined, are shown not to directly predispose individuals to IDDM. This result does not discount the possibility that subdivision of the DR antigens will yield the predisposing agents. In Caucasian populations, after consideration of the predisposing effect of the antigens DR3 and DR4, the protective effect of DR2 in predisposition is demonstrated. Additionally, DR1 and possibly DRw8 exhibit a higher than expected frequency in patients.

Alleles↗
PubMed1984

The affected sib method. III. Selection and recombination.

The affected sib-pair method has been used to investigate the mode of inheritance, and to estimate the "disease" allele frequency, for a number of HLA-associated diseases. One of the assumptions of the original sib-pair method is that the disease confers no selective disadvantage on affected individuals. This is obviously not the situation for most diseases. We have determined the expected HLA haplotype-sharing distribution among affected sib-pairs when selection against individuals with the disease is taken into account. We have shown that if the mode of inheritance of the selectively disadvantageous disease is recessive or additive, the original affected sib-pair analysis, ignoring selection, still estimates the true mode of inheritance, but usually yields an underestimate of the "disease" allele frequency. For intermediate and dominant models of disease predisposition, both the estimates of the degree of penetrance of the "disease" genotypes, and the "disease" allele frequency, are altered if selection is ignored in the analysis. Similarly, allowing for recombination between the "disease" locus and the HLA region does not affect the determination of the mode of inheritance of the disease if it is recessive or additive; in other cases, however, the estimate of the mode of inheritance is affected. The "disease" allele frequency is overestimated when nonzero recombination is ignored for all the modes of inheritance that have been studied.

Alleles↗
PubMed1983

The human histocompatibility system: anthropological considerations.

The human histocompatibility system (HLA) is a linked complex of genes on human chromosomes 6. Many of the loci in this region are highly polymorphic. This endows the system with unique differentiating powers, both in terms of the population genetics of the reconstruction of evolutionary trees to assess biological divergences (or affinities) in human populations, and in terms of detecting the genetic component of the many diseases which show an association with certain variants (alleles) of the HLA system. Different racial groups often exhibit different HLA disease associations; that is, a different allele is associated with the disease in different populations, although in some cases the same allele is associated with the disease in all populations. The classical example of this latter situation is the association of B27 with ankylosing spondylitis. This disease will be used as an example to illustrate how population observations allow inferences to be made regarding the evolutionary histories of the HLA-associated diseases, as well as the genetic mechanisms of the diseases.

Chromosomes, Human, 6-12 and X↗
PubMed1983

Evidence for balancing selection at HLA.

HLA data from the A and B loci for 22 populations were compared with the neutrality expectations from Ewens' sampling theory. In 25 of 44 cases, there was significantly less homozygosity than expected. Although a number of factors can affect homozygosity in this manner, upon close examination only symmetrical balancing selection appears to be consistent with these data.

Female↗
PubMed1983

Investigation of the mode of inheritance of the HLA associated diseases by the method of antigen genotype frequencies among diseased individuals.

Statistical features of the method of antigen genotype frequencies among the diseased, for single and multiple disease associations at a locus, will be presented. A methodology to determine when a true intermediate mode of inheritance can be distinguished from strict recessive or additive inheritance will be developed. The effect of sporadics and ascertainment bias on the observed antigen genotype frequencies will be investigated. Data on ankylosing spondylitis, multiple sclerosis and dermatitis herpetiformis are very close to expectations for an additive (or dominant) mode of inheritance for the HLA-linked disease-predisposing gene, and data on hemochromatosis, insulin dependent diabetes mellitus and celiac disease are close to recessive expectations. If an intermediate model does apply in any of these cases, it must be an intermediate model that is fairly close to a strict recessive or dominant model; as appropriate. DR data for insulin dependent diabetes mellitus (IDDM) strongly indicate that there are two separate "disease" alleles, which exhibit negative complementation, predisposing individuals to IDDM, where the mode of inheritance of the "disease" alleles considered separately is close to recessive. In general, this method cannot rule out the existence of sporadics or a second disease-predisposing gene, when the penetrance values over the two disease-predisposing genes are strictly additive, for diseases showing agreement with additive (or dominant) modes of inheritance.

Arthritis, Juvenile↗
PubMed1983

The affected sib method. II. The intermediate model.

An iteration procedure is outlined which uses HLA haplotype sharing data from sib pairs in which both sibs have the disease of interest. The procedure allows estimation of the degree of dominance of the HLA linked 'disease' allele, and its frequency in the population, for intermediate models where it is assumed that individuals who do not have at least one copy of the 'disease' allele do not contract the disease. Parameter estimates from sib-pair data on multiple sclerosis, insulin dependent diabetes mellitus, haemochromatosis, coeliac disease juvenile rheumatoid arthritis, and Graves' and Hashimoto's diseases are given.

Alleles↗
PubMed1981

Solitary ulcer of the rectum--or is it? A report of 6 cases.

Solitary ulcer of the rectum is an unusual disorder which presents only occasionally to the individual clinician. While the histopathological features are characteristic, the wide variety of naked eye appearances of lesions which the syndrome produces may make for clinical confusion, particularly since the lesions may be neither solitary nor ulcerated. We present to the Victoria Infirmary, Glasgow, over the period 1969-79 which illustrate the diagnosis dilemma and variety of lesions encountered.

Adult↗
PubMed1981

Measuring the strength of associations between HLA antigens and diseases.

The strength of the population association between an antigen and a disease can be estimated not only by the relative risk value, but also by what variously has been called the population attributable risk and the etiologic fraction. This alternative measure has certain advantages if the association is due to linkage disequilibrium between the antigen allele and a "disease" allele at a closely linked "disease susceptibility" locus. In particular, it can then be used to determine which of many antigens associated with the same disease has the strongest association from a genetical point of view.

Epidemiology↗
PubMed1981

Hypersensitivity to tobacco glycoprotein in human peripheral vascular disease.

One hundred and sixty-four patients with peripheral vascular disease (PVD) were skin tested with a purified tobacco glycoprotein (TGP). A basophil degranulation test (BDT) was also performed to assess in vitro reactivity to TGP. Immediate skin test hypersensitivity to TGP was found in 18 of 164 (11%) patients with radiologically demonstrable PVD. BDT was positive in 25/42 (60%) smokers as opposed to 6/23 (24%) nonsmokers (p less than 0.01). Twenty-one of 49 (43%) skin test-negative and 10/11 (91%) skin test-positive patients wih PVD had a positive BDT (p less than 0.02). Only 1/34 (3%) patients with negative BDT had a positive skin test. Skin test-positive patients had significantly higher BDT at 0.01 and 0.001 microgram/ml TGP in vitro compared to skin test-negative patients (p less than 0.01). When PVD was graded by arteriography, one of 11 patients with "mild," 11/87 with "moderate" and 4/20 with "severe" PVD were skin test-positive to TGP (p less than 0.01 "mild" vs "moderate"; p less than 0.05 "mild" vs. "severe"). These differences could not be attributed to age, sex, atopy or smoking status. Reactivity to TGP exists in a proportion of patients with PVD and may be causally related in such cases to the development of atherosclerotic vascular disease.

Adult↗
PubMed1980

Giant intracranial aneurysms: diagnosis with special reference to computerised tomography.

The clinical presentation, radiological investigations and surgical management of 11 patients with giant intracranial aneurysm (greater than 2.5 cm) have been reviewed. Most patients had signs and symptomd haemorrhage. The most helpful plain film finding was intracranial calcification. This varied from a mere fleck to the classical curvilinear variety. Computerised tomography (CT) scans were available on all 11 patients. All showed a space-occupying lesion of high density. Two types of enhancement were seen following intravenous contrast medium, (a) homogeneous and (b) rim enhancement with or without a patchy increase in density centrally. The CT appearances in some of the cases resembled those shown by other lesions such as neoplasm. Arteriography in almost all cases demonstrated the aneurysm but often under-estimated its size. On two occasions the aneurysm did not fill and the nature of the lesion demonstrated on the plain CT remained unconfirmed. Direct surgical attack rather than carotid ligation was the operation of choice. Most patients responded very well to this treatment.

Adolescent↗