Search PubMed⌕ Search

Biomedical subjects

G Thomson

Publications and source records attributed to G Thomson.

At least 127 records · Page 7Linked to original sources
PubMed1986

A two-locus neutrality test: applications to humans, E. coli and lodgepole pine.

The expected disequilibrium between two loci with k alleles at one locus and l alleles at the other is given for a sample of size n drawn from a population under neutrality equilibrium. Three different measures of disequilibrium with 95% intervals are tabulated for combinations of n, k, l and 4Nc, where N is the effective population size and c is the amount of recombination between the loci. The extent and pattern of disequilibrium are strongly dependent upon 4Nc and are somewhat dependent on n, k and l. The 95% intervals are large, particularly for low numbers of alleles and low values of 4Nc. As examples, observed disequilibrium from histocompatibility loci in humans (HLA) and electrophoretic data in E. coli and lodgepole pine were compared to these theoretical values. Using information about recombination rates, the HLA data showed more disequilibrium than neutrality expectations, whereas electrophoretic data from E. coli and lodgepole pine had somewhat less disequilibrium than neutrality expectations.

Alleles↗
PubMed1986

Charge changes in protein evolution.

The number of charge changes relative to total amino acid replacements for each of seven protein sequences (cytochrome c, hemoglobin alpha, hemoglobin beta, myoglobin, insulin, and fibrinopeptides A and B) has been studied. This number was compared with the expected value obtained under the assumption of random nucleotide substitution. The results obtained indicate that four proteins--hemoglobin alpha, hemoglobin beta, myoglobin, and insulin--are accumulating charge changes at rates slower than those predicted by a model of random substitution. Cytochrome c and fibrinopeptides A and B are accumulating charge changes at rates similar to those predicted by a random model.

Animals↗
PubMed1986

Genetics of rheumatoid arthritis.

The haplotype sharing distribution in affected sib pairs are used to demonstrate the linkage of a susceptibility gene for rheumatoid arthritis (RA) to the HLA region. Family and population studies suggest heterogeneity in the etiology of RA.

Alleles↗
PubMed1986

Three-allele synergistic mixed model for insulin-dependent diabetes mellitus.

Application of the method of antigen genotype frequencies among patients to HLA-DR data pertaining to insulin-dependent diabetes mellitus substantiates the results of Rotter et al. and Thomson that a single-predisposing-allele model is incompatible with the observed data. The method is also modified to take into account the possibility of blanks (untyped antigens) in the assumed homozygotes. The rejection of all intermediate single-allele models is still obtained. A minimum of two HLA-linked predisposing components are necessary to account for the data. The patterns observed are consistent with a three-allele model, in which the two predisposing alleles interact synergistically (negative complementation). Furthermore, a model in which the DR3-associated predisposition allele is recessive in the absence of the other allele and the DR4-associated predisposing allele is additive (dominant) in the absence of the other is more consistent with the data than a model in which both alleles are recessive or additive in the absence of the other.

Alleles↗
PubMed1986

Determining the mode of inheritance of RFLP-associated diseases using the affected sib-pair method.

It is determined that the classical HLA sib-pair method can be used for the detection of linkage and determination of mode of inheritance of a disease when applied to non-HLA data, where attention is restricted to that subset of all parental matings that can produce affected sibs where unequivocal determination of haplotype sharing by descent values can be obtained. With the increasing use of restriction fragment length polymorphisms (RFLPs) to detect disease genes, it is predicted that this method will be applicable to many diseases.

DNA Restriction Enzymes↗
PubMed1986

Contrasting evolutionary histories among tightly linked HLA loci.

Genes comprising the major histocompatibility complex (MHC) play a central role in governing the immune response of vertebrates. A great deal of information has been revealed on the molecular biology and physiology of these loci, but three features-the high polymorphism, tight linkage among the loci, and the nonrandom association of alleles-make the system of particular interest from the perspective of population genetics. Information on the dynamic evolutionary forces that have acted on a locus can be inferred from the number and distribution of alleles that it carries. Ten loci from the HLA region of the human MHC, each sampled from several different populations, have been examined for departures from the expected value of homozygosity under the condition of selective neutrality. The homozygosities of five class I and II loci that code for membrane glycoproteins, HLA-A, -B, -C, -DR, and -DQ, and of glyoxylase I (GLO) were significantly less than the neutrality expectations. This suggests the presence of some form of balancing selection. In spite of being closely linked, in fact, located between the class I and class II histocompatibility loci, the homozygosities of the four class III or complement loci C2, Bf, C4A, and C4B, which are detected by electrophoresis, were indistinguishable from, or exceeded, that expected under neutrality. Although this conforms to the suggestion that, in general, electrophoretic variants are neutral, because of the tight linkage to loci demonstrating a history of selection, it is possible that the mechanism for generating variation in the class III loci may be different from that of the class I and class II loci.

Alleles↗
PubMed1985

The affected sib method. I. Statistical features of the affected sib-pair method.

The distribution of the number of HLA haplotypes shared by sibs affected with the same HLA-linked disease can be used to obtain information on the genetics of the disease. Since the inception of the use of sib-pair methods for the analysis of the HLA-associated diseases, the question has been raised of how to include families with more than two affected sibs in the sib-pair analysis. This paper presents appropriate weighting schemes. A procedure for estimating the frequency of the disease allele in the general population, under the assumptions of single-allele recessive, additive, dominant and intermediate models, with negligible recombination (theta = 0) between the disease-predisposing gene and the HLA region, and no selective disadvantage of the trait, is also given. Cluster-sampling techniques are used in the analysis.

Alleles↗
PubMed1985

Analysis of negative and multiple HLA antigen disease associations.

The nature and extent of negative and multiple HLA antigen disease associations are investigated theoretically under two models. The first model assumes that an HLA antigen is involved directly in predisposing individuals to disease. The second model assumes that the association of a particular HLA antigen(s) with a disease is the result of linkage disequilibrium between the allele determining the antigen and alleles at a nearby locus which confers susceptibility to disease. We determined whether observed decreases in antigen frequencies among a patient group are simply the inevitable result of the fact that if one or more alleles at a locus is increased in frequency, then others must be decreased. Under the antigen predisposing model exact predictions concerning allele and antigen class frequencies at the predisposing locus, and the non-predisposing loci, are given. The predictions are examined using HLA-DR data for multiple sclerosis.

Alleles↗
PubMed1985

The affected sib method. IV. Sib trios.

The classical sib pair method uses the expected and observed HLA (human leukocyte antigen) haplotype sharing distribution in sib pairs, who are affected with an HLA associated disease, to make inferences about the inheritance of the disease. In this paper we present the expected HLA haplotype sharing distributions in affected sib trios, and sib pairs, from families with three or more affected sibs. The underlying model for both distributions, as for the classical sib pair method, is that disease predisposition is determined by a single allele at an HLA-linked locus. The sib trio tests of hypotheses (additive and recessive), and disease parameter estimates (additive, recessive and intermediate), can be compared with those obtained from the classical sib pair analysis. In addition, the sib trio data allow parameter estimation for a general disease model to be made, if the data fall within the bounds of the expectation. This study forms the basis of later investigations which show that haplotype sharing of affected sib trios for two susceptibility alleles (negative complementation) model, which appears appropriate for insulin dependent diabetes mellitus (IDDM), moves outside the bound of the single susceptibility expectations outlined here, whereas haplotype sharing values for sib pairs are bound by the single susceptibility allele expectations. Available Caucasian IDDM data have been analysed. The results support genetic heterogeneity of IDDM.

Diabetes Mellitus, Type 1↗
PubMed1984

Wound sepsis after low risk elective cholecystectomy: the effect of cefuroxime.

A prospective randomized double-blind study was performed to assess the value of a single intravenous injection of 1.5 g cefuroxime in the prevention of wound sepsis after low risk elective cholecystectomy. Wound infection developed in 10 of 81 control patients compared with 2 of 79 treated patients (P less than 0.05). Wound sepsis occurred more commonly in patients with infected bile or with a positive culture from a closing wound swab. Cefuroxime significantly reduced the isolation of staphylococci but not other organisms from the closing wound swab and also produced a significant reduction in wound infection in patients with sterile bile.

Cefuroxime↗
PubMed1984

A new clamping and stretching procedure for determination of collagen fiber stiffness and strength relations upon maturation.

Clamping of tendon fibers is a major concern in connective tissue biomechanics. We present here a new clamping method. Also the stretching procedure is different from the conventional extension until the point of failure. Thus we have used a procedure of interval stretches, where 0.01 extensions during 2.5 s are succeeded by periods of relaxation. This procedure reduces the stress on clamps and transducers which causes serious problems in conventional extensions of some older specimen. The influence of stretching rate and periods of relaxation on the observed values of stiffness has been tested and discussed. The fibers from rat tail tendons only show a minor increase in stiffness between 40 day and 90 day old animals, and do not show significant changes from the age of 90 to 240 days. The values of stiffness expressed as Young's modulus of elasticity, had maximal values of 1.2, 1.8 and 1.9 kNmm-2 at the three ages investigated. The fiber strength, however, increases dramatically, thus the ultimate value was 18 Nmm-2 for 40 day old fibers, while at 90 days and 240 days it had increased to 102 Nmm-2 and to 106 Nmm-2, respectively.

Age Factors↗
PubMed1984

Third order linkage disequilibrium.

For third order linkage disequilibrium there is a constraint on the maximum value the disequilibrium can take, given pairwise disequilibria values and allele frequencies. As distinct from second order disequilibrium (considered in the context of a two locus model) there is also in some cases a constraint on the minimum value. The appropriate procedures to determine these maximum and minimum values are given, as well as numerical values utilizing HLA data.

Alleles↗