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• W1986435148 abstract "Among variants selected in a human cell line for nonexpression of a single gene product in the HLA complex, most are single-gene variants, but several have been isolated that are cis -acting and abolish expression of a series of closely linked genes. The two most plausible mechanisms by which such variants could arise are mitotic crossing-over and chromosome deletion. In two HLA variants the presence of a visible chromosome deletion, a 50% reduction in activity of glyoxalase I (a closely linked marker), or both provided evidence for deletional origins. In a third variant these changes were not demonstrable. All three variants showed reductions in amount of cell surface HLA antigens: 40% for the Ia antigens (HLA-DR) and 20-25% for HLA-ABC antigens. The reductions in cell surface antigen in deletion variants have an important implication: in the case of the HLA-A, -B, and -C heterodimer, which consists of a subunit coded for within the major histocompatibility complex and another subunit (β 2 -microglobulin) coded for on a different chromosome, it is the gene of the major histocompatibility complex that is limiting. The nonmutant haplotype includes A2 ; binding of an A2 monoclonal antibody in two of the mutants was found to be approximately equal to that in the wild-type cells. Thus, loss of one copy of HLA-ABC genes does not lead to gene dosage compensation—i.e., increased activity by the remaining ABC alleles. The results with the two types of antibodies support a deletional mechanism and are inconsistent with mitotic crossing-over. Of interest with respect to the potential use of deletion variants for purposes of mapping is the fact that each of these variants has distinctive breakpoints. The absence of mitotic crossing-over in 1.2 × 10 7 cells selected suggests that the event is rare in this autosomal region, if it occurs at all." @default.
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• W1986435148 date "1982-02-01" @default.
• W1986435148 modified "2023-10-14" @default.
• W1986435148 title "Gene dosage and gene expression in the <i>HLA</i> region: Evidence from deletion variants" @default.
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• W1986435148 doi "https://doi.org/10.1073/pnas.79.4.1235" @default.
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