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Biomedical subjects

D N Propert

Publications and source records attributed to D N Propert.

At least 19 recordsLinked to original sources

GM and KM allotypes and GM RFLP allogenotypes in Micronesians from Nauru.

Immunoglobulin allotypes of the GM and KM systems were determined in a sample of Micronesian subjects from Nauru. Four GM haplotypes were identified in the sample: GM*1,3 23 5, 10,11,13,14, GM*1,17 23' 21, GM*1,3 23' 5,10,11,13,14, and GM*1,2,17 23' 21, although the last of these may have been introduced by non-Micronesian admixture. The frequency of the KM*1 allele is 0.115 +/- 0.033, which is slightly lower than reported in Micronesians from the Caroline Islands. RFLPs generated by the enzymes Taq I and Pvu II and detected by a Hu gamma 4 probe were related to GM phenotypes. The haplotypes GM*1,3 +/- 23 5,10,11,13,14 were strongly associated with a Taq I 5.0-kb band. The presence and absence of the allotype G2M 23 were marked by a Pvu II 7.0 + 2.0 kb pair and a Pvu II 9.0-kb fragment, respectively. GM*1,17 23' 21 was strongly associated with a Pvu II 5.0 + 2.7 kb pair. The different relationships between GM haplotypes and Hu gamma 4 RFLPs in Micronesians and Caucasians indicate that a universal GM allogenotyping procedure cannot yet be developed; instead, population-specific procedures are necessitated by differences in GM allotype arrangements between populations.

Gene Frequency

ABO blood groups in hematologic malignancies.

This article examines the genetic predisposition of individuals to lymphoma and leukemia with regard to the ABO blood groups. Blood samples from 558 patients suffering from various forms of lymphoma and leukemia were collected and typed for ABO blood groups. The ABO blood group phenotype frequencies of lymphoma patients were similar to those in control samples. Among leukemia patients, a significant increase in the frequency of the A2 phenotype was found in chronic lymphocytic leukemia. Possible mechanisms underlying the predisposition of individuals with the A2 blood group to chronic lymphocytic leukemia suggested by these preliminary results are discussed.

ABO Blood-Group System

An immunologic and genetic study of asthma in workers in an aluminum smelter.

The cause or causes of asthma among employees in aluminum smelters is unknown. We attempted to ascertain whether such workers who developed asthma differed in respect to indices of immunological function and certain genetic markers. Data were collected from 33 asthmatic and 127 nonasthmatic potroom workers. Asthmatic workers had significantly lower mean serum levels of immunoglobulin (Ig)M; however, mean levels of IgG and IgA, median levels of IgE, the capacity for recall of delayed type hypersensitivity, levels of immune complexes, and frequency of antinuclear or other autoantibodies did not differ from values for nonasthmatic workers. Asthma was found to develop on a background of atopy in 21 workers (64%), whereas there were no features of atopy in 12 workers (36%). Cigarette smoking had independent effects on immunological function. In respect to genetic markers, there was a higher frequency among asthmatic workers of the alpha-1-anti-trypsin deficiency phenotype MS, but the frequency of blood groups, Gm allotypes, or human leucocyte antigen types was similar. The study established that the profile of immune function, or genetic markers tested, did not differ essentially for workers in an aluminum smelter who did or did not develop asthma; however, there was an indication of heterogeneity in causation, as judged by "atopy-related" and "non-atopy-related" groups in the asthma population.

Adult

Immunoglobulin allotypes Gm and Km in hematologic malignancies.

Immunoglobulin allotypes of the Gm and Km systems have been compared in patients with various forms of hematologic malignancies and healthy controls of the same ethnographic background. These comparisons found an increased frequency of the haplotype Gm and a decreased frequency of Gm in patients with Hodgkin's disease; a decreased frequency of Gm in diffuse, large-cell lymphoma patients; a decreased frequency of Gm and an increased frequency of Gm in acute myeloid leukemia patients; a decreased frequency of Gm in chronic myeloid leukemia patients, and an increased frequency of the phenotype Km(1+) in chronic lymphocytic leukemia patients. These results support previous suggestions of the involvement of immunoglobulin allotypes in the susceptibility to some forms of human hematologic malignancy.

Gene Frequency

Gm typing by immunoglobulin heavy-chain gene RFLP analysis.

This study was undertaken to investigate a means of assigning Gm allotypes to Caucasians by RFLP analysis. A single immunoglobulin heavy-chain gamma-4 cDNA probe (HU gamma 4) was hybridized with genomic DNA digested separately with two restriction enzymes, TaqI and PvuII. Results showed excellent correlation (P less than .001) between serologically defined Gm allotypes G1m(1), G1m(2), G2m(23), and G1m;G3m (3;5,10) and RFLPs identified with the (HU gamma 4) probe. We conclude that it is now possible to define common Gm haplotypes in Caucasians by RFLP analysis. This method provides a useful adjunct to serological allotyping and indeed has several important advantages over traditional serology: it allows confident Gm assignment and the definition of homozygous and heterozygous Gm arrangements, is highly reproducible, and is readily executed in any molecular genetic laboratory.

Cloning, Molecular

Genetic markers in Australian Caucasian subjects with coeliac disease.

A group of 69 unrelated Australian coeliac subjects (41 adult onset and 28 childhood onset) were typed for for HLA-A, B, DR and DQ antigens. Immunoglobulin allotypes were also determined in 36 of these patients. An association between coeliac disease and the antigens DR3, DR7 and DQw2 was confirmed in this population. There was no significant difference in antigen frequencies between childhood and adult onset coeliac disease, although the association with DR7 was stronger in the childhood group. All coeliac patients who did not carry DR3 or DR7 were found to be DR4 positive. No association was demonstrated between coeliac disease and any immunoglobulin allotype, either in the absence of HLA antigens B8 and DR3 or in male coeliac patients.

Australia

Occurrence of the immunoglobulin haplotypes Gm1,17;23;21 and Gm1,2,17;23;21 in a sample of Australian Caucasians.

Phenotypes positive for G2m(23) but negative for G1m(3) and G3m(5,10,11,13,14) are generally very infrequent in Caucasian populations. We recently Gm typed 372 Australian blood donors, predominantly of European descent, and found two Gm(1;23) and five Gm(1,2;23) individuals among them. This finding suggests that the haplotypes Gm1,17;23;21 and Gm1,2,17;23;21 may occur, in some European populations, with a frequency considerably higher than has been generally assumed.

Australia

Interaction between HLA antigens and immunoglobulin (Gm) allotypes in susceptibility to type I diabetes.

HLA-A,B,C and DR typing was performed on 108 Caucasian type I diabetic patients, 68 being Gm typed. The expected association with B8, B18, Bw62, DR3 and DR4 was observed as well as an excess of DR3/4 heterozygotes. DR2 was decreased in frequency. In the total patient group, no Gm association was observed but when the patients were subgrouped according to HLA type, HLA/Gm interactive effects were seen. An increase in Gm(1,3;5) was observed in DR3 positive, DR4 negative patients. This association occurred predominantly in females (compared with DR4 and DR3/4 patients of the same Gm phenotype who were predominantly male). Further genetic heterogeneity was identified within DR3/4 patients. Within this group, Bw62 was increased (strongly suggestive of Bw62-DR4 haplotypes) within B8, Gm heterozygotes compared with B8, Gm homozygotes. This finding can be interpreted as indicating a three-way interaction between genes on two HLA haplotypes and Gm-linked genes. These results reflect the genetic heterogeneity and complexity of insulin-dependent diabetes mellitus and explain in part the previous failure of simple genetic models to adequately explain inheritance patterns observed.

Diabetes Mellitus, Type 1

Genetic linkage analysis of epidermolysis bullosa simplex, Köbner type.

Genetic linkage relationships between a range of marker loci and the locus for epidermolysis bullosa simplex (EBS), Köbner type, were examined in a single kindred. A positive lod score of 1.2 at theta = 0.2 was found for Fy. To test the clinical observation that Köbner and Weber-Cockayne types may be the same disease determined by different alleles, published lod scores from definite Weber-Cockayne families were added to those from this study. A lod score of 1.8 was found at theta = 0.2. This value falls to 1.5 at theta = 0.2 when all families other than Ogna type are included. The Köbner variant studied is not closely linked to GPT and is therefore distinct from EBS1 (Ogna type). Linkage analysis is consistent with an hypothesis that Köbner and Weber-Cockayne types are determined by a single locus; however, further evidence is needed before this locus can be designated EBS2 and assigned to chromosome 1.

Chromosome Fragility

A strong association between the antinuclear antibody anti-La (SS-B) and the kappa chain allotype Km(1).

The distribution of immunoglobulin allotypes of the Gm and Km systems was examined in 51 patients with antinuclear antibodies (ANA), which reacted with two saline-extractable non-DNA nuclear antigens, anti-La (SS-B) and anti-RNP, which characterize certain multisystem autoimmune diseases. Forty-six percent of the 26 patients with anti-La were positive for the Km(1) allotype compared with 14% of the 35 with anti-RNP and 16% of 1204 of healthy subjects (corrected P value less than 0.005). The high frequencies of the Km(1) allotype (46%), female sex (100%), and the HLA-B8, DR3 phenotype (greater than 90%) in patients with anti-La are indicative of a substantial inherited predisposition to the development or expression of this autoantibody. The strong association between the Km(1) allotype and the anti-La response may be due to linkage disequilibrium between genes coding for the constant region of immunoglobulin kappa light chains and genes coding for the variable regions of kappa light chains which confer antibody specificity for the special configuration of the ribonucleoprotein known as La.

Antibodies, Antinuclear

Gm allotypes and multiple sclerosis.

Immunoglobulin allotypes (Gm) were analysed in 40 multiple sclerosis (MS) patients and the distribution of phenotypes compared to that in 1220 healthy controls. The frequencies of GM(1) and Gm(1, 2) are significantly increased inthe patients suggesting that the presence of the Gm3;5, 13, 14 haplotype confers a resistance to the development of MS.

Female

HLA antigens and affective illness.

HLA-A and B locus antigens were determined in 96 affectively ill persons including 25 unipolar and 47 bipolar patients. The frequency of HLA-A28 is higher than in controls in each patient group. HLA-Bw16 is present with an elevated frequency among the unipolar patients. These differences are no longer significant when corrected for the number of antigens tested. The literature on HLA antigens in affective illnesses is reviewed and possible reasons for the seemingly conflicting results found to date are briefly discussed.

Gene Frequency

Presymptomatic detection of Huntington's disease.

Because of the usually late onset of Huntington's disease (HD) most sufferers have reproduced and passed the HD gene to about one half of their offspring before they themselves develop symptoms of the disease. Genetic counseling of persons at risk of HD would be greatly facilitated if the gene could be detected presymptomatically. At present, there is no suitable predictive test for HD, but many approaches currently being investigated show some promise. These approaches are reviewed and critically evaluated.

Genetic Carrier Screening