Somatic Cell Genotoxicity at the Glycophorin A Locus in Humans
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Progress in Clinical and Biological Research
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We have developed an assay for detecting variant erthrocytes that occur as a result of in vivo allele loss at the glycophorin A (GPA) locus on chromosome 4 in humans. This gen codes for an erythroid-specific cell surface glycoprotein, and with our assay we are able to detect rare variant erythrocytes that have lost expression of one of the two GPA alleles. Two distinctly different variant cell types are detected with this assay. One variant cell type (called N∅) is hemizygous. Such cells might arise by mutation, deletion or inactivation of the GPA(M) allele or loss of the chromosome carrying that allele in erythroid precursor cells. Our assay also detects homozygous variant erythrocytes that have lost expression of the GPA(M) allele and express the GPA(N) allele at twice the heterozygous level. These are termed NN cells and might be generated by chromosomal loss and duplication, gene conversion or mitotic recombination in erythroid precursor cells in the bone marrow. An important feature of the assay is that it requires continued expression of one of the two allelic forms of GPA to guarantee that all variant cells are capable of normally expressing this cell surface antigen. Because of this built-in safeguard, erythrocytes that have epigenetically lost the capability to retain any cell surface GPA (e.g., be membrane defects, carbohydrate metabolism defects, or by cellular degeneration) are not includes as false positives (phenocopies) in the enumeration of variant cells.
Medical Specialties | Medicine and Health Sciences | Osteopathic Medicine and Osteopathy
Jensen, Ronald H.; Grant, Stephen G.; Langlois, Richard G.; and Bigbee, William L., "Somatic Cell Genotoxicity at the Glycophorin A Locus in Humans" (1991). College of Osteopathic Medicine Faculty Articles. 1305.