alexa In vivo somatic mutation and segregation at the human glycophorin A (GPA) locus: phenotypic variation encompassing both gene-specific and chromosomal mechanisms.
Molecular Biology

Molecular Biology

Journal of Cytology & Histology

Author(s): Grant SG, Bigbee WL

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Abstract The human in vivo GPA assay uses immunolabelling and flow cytometry to directly detect and quantitate somatic variation in erythrocytes expressing glycophorin A (GPA) allele-loss phenotypes in peripheral blood samples from individuals heterozygous for the MN blood type. The assay distinguishes two independent classes of variant cells: those that have lost expression of one allelic form of the GPA cell surface protein (the antigen responsible for the MN blood type), and a second class that, in addition to this allele loss now express the remaining homologue at twice the level of the heterozygote. This assay has been widely applied in human populations; both classes of variant appear at frequencies of approximately 10(-5) in unexposed individuals. There is considerable inter-individual variation, however, as well as an increase in variant cell frequency with age. Exposure to genotoxic agents such as ionizing radiation or chemical mutagens cause a dose-dependent increase in the frequency of variants, and the assay has been proposed as a quantitative cumulative biodosimeter for accidental, environmental, occupational and medical exposures to these agents. Variants arising by such molecular mechanisms as recombination, gene inactivation and chromosome missegregation, as well as classical mutation are detectable by this assay, hence the term somatic segregation rather than simply somatic mutation. Indeed, the spectrum of molecular events contributing to the two classes of GPA variants are identical to those involved in the etiology of recessive cancer, and largely representative of the activating events occurring at proto-oncogenes. The GPA assay has therefore also been proposed as an intermediate biomarker of carcinogenesis and other human diseases characterized by somatic mosaicism.
This article was published in Mutat Res and referenced in Journal of Cytology & Histology

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