Mutations in human lymphocytes studied by an HLA selection system

Janatipour, Mahmoud; Trainor, Kevin J.; Kutlaca, R.; Bennett, Gregg; Hay, Judith; Turner, David R.; Morley, Alexander A.

doi:10.1016/0027-5107(88)90058-9

Cited by 74 publications

(19 citation statements)

References 16 publications

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“…The method of complement-mediated cytotoxicity (CMC) for the isolation of mutant lymphocytes that have lost HLA-A2 [25] was modified for the successful isolation of similar mutants from lymphoblastoid cell lines [26]. Briefly, to isolate cells which had lost the HLA-A2 antigen, two successive rounds of incubation were applied with an anti-HLA-A2 The structure of a hypothetical allele is shown.…”

Section: Specific Mutation Assaysmentioning

confidence: 99%

Molecular methods for the detection of mutations

Monteiro

Marcelino

Conde

et al. 2000

Teratog. Carcinog. Mutagen.

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We report the results of a collaborative study aimed at developing reliable, direct assays for mutation in human cells. The project used common lymphoblastoid cell lines, both with and without mutagen treatment, as a shared resource to validate the development of new molecular methods for the detection of low-level mutations in the presence of a large excess of normal alleles. As the "gold standard, " hprt mutation frequencies were also measured on the same samples. The methods under development included i) the restriction site mutation (RSM) assay, in which mutations lead to the destruction of a restriction site; ii) minisatellite length-change mutation, in which mutations lead to alleles containing new numbers of tandem repeat units; iii) loss of heterozygosity for HLA epitopes, in which antibodies can be used to direct selection for mutant cells; iv) multiple fluorescence-based long linker arm nucleotides assay (mf-LLA) technology, for the detection of substitutional mutations; v) detection of alterations in the TP53 locus using a (CA) array as the target for the screening; and vi) PCR analysis of lymphocytes for the presence of the BCL2 t(14:18) translocation. The relative merits of these molecular methods are discussed, and a comparison made with more "traditional" methods.

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Section: Specific Mutation Assaysmentioning

confidence: 99%

Molecular methods for the detection of mutations

Monteiro

Marcelino

Conde

et al. 2000

Teratog. Carcinog. Mutagen.

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“…Hypoxanthine-guanine phosphoribosyltransferase (hprt) and hla-a mutants can be detected in lymphocyte preparations [Albertini et al, 1982;Morley et al, 1983;McCarron et al, 1986;Janatipour et al, 1988]. Mutants at the glycophorin A locus (gpa) can be detected in peripheral blood red cell samples [Langlois et al, 1986[Langlois et al, , 1990Grant and Bigbee, 1993;Jensen and Bigbee, 1996].…”

Section: Introductionmentioning

confidence: 98%

Estimation of mutation rate at human glycophorin A locus in hematopoietic stem cell progenitors

Vickers

Hoy

Lake

et al. 2002

Environ and Mol Mutagen

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Surveys of human mutant cells exhibit a few individuals with relatively high "outlying" values, which might be explained by rare mutations occurring during development. To estimate how commonly this occurs, mutant red cell frequencies at the glycophorin A locus in 135 neonates and 109 children and adolescents from three research centers are compared with simulations in which mutations arise from successive cycles of binary fission. The simulations predict the data most accurately when the mutation rate in stem cell precursors is about 2-4 x 10(-7) per division cycle, which is similar to previous estimates from adult stem cell divisions. If these mutation rates are accurate, and the number of stem cell divisions during adult life is as low as previously estimated, it is predicted that up to one-sixth of mutant stem cells over a lifetime arose in early life. However, these mutant stem cells would be difficult to detect in surveys because their distribution within the general population is so skewed.

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“…Several somatic mutation assays have been established for the glycophorin A (GPA) genes in erythrocytes (3,4) and for the hypoxanthine phosphoribosyltransferase (hprt) (5,6), HLA-A (7,8), and TcRa and P genes (9,10) (4,11,12), and the TcR assay has potential value as a biological dosimeter for those experiencing recent or chronic radiation exposure (13,14).…”

Section: Introductionmentioning

confidence: 99%

Monitoring Exposure to Atomic Bomb Radiation by Somatic Mutation

Akiyama¹,

Kyoizumi²,

Kusunoki³

et al. 1996

Environmental Health Perspectives

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Atomic bomb survivors are a population suitable for studying the relationship between somatic mutation and cancer risk because their exposure doses are relatively well known and their dose responses in terms of cancer risk have also been thoroughly studied. An analysis has been made of erythrocyte glycophorin A (GPA) gene mutations in 1,226 atomic bomb survivors in Hiroshima and Nagasaki. The GPA mutation frequency (Mf) increased slightly but significantly with age at the time of measurement and with the number of cigarettes smoked. After adjustment for the effect of smoking, the Mf was significantly higher in males than in females and higher in Hiroshima than in Nagasaki. All of these characteristics of the background GPA Mf were in accord with those of solid tumor incidence obtained from an earlier epidemiological study of A-bomb survivors. Analysis of the dose effect on Mf revealed the doubling dose to be about 1.20 Sv and the minimum dose for detection of a significant increase to be about 0.24 Sv. No significant dose effect for difference in sex, city, or age at the time of bombing was observed. Interestingly, the doubling dose for the GPA Mf approximated that for solid cancer incidence (1.59 Sv). And the minimum dose for detection was not inconsistent with the data for solid cancer incidence. The dose effect was significantly higher in those diagnosed with cancer before or after measurement than in those without a history of cancer. These findings are consistent with the hypothesis that somatic mutations are the main cause of excess cancer risk from radiation exposure. Environ Health Perspect 1 04(Suppl 3): 493-496 (1996)

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Mutations in human lymphocytes studied by an HLA selection system

Cited by 74 publications

References 16 publications

Molecular methods for the detection of mutations

Molecular methods for the detection of mutations

Estimation of mutation rate at human glycophorin A locus in hematopoietic stem cell progenitors

Monitoring Exposure to Atomic Bomb Radiation by Somatic Mutation

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