title: Molecular nature of in vivo mutations in human cells at the autosomal HLA-A locus.
abstract: The mutations present in vivo in normal human cells were studied at the HLA-A locus by isolating mutant lymphocytes using antibody-complement immunoselection and cloning at limiting dilution. The molecular basis for mutation in 127 mutant lymphocytes from 10 individuals was determined by studying a variety of polymorphic gene loci on both arms of chromosome 6. No change was detected in 78 mutants (61.4%), gene deletion was detected in 11 (8.7%), and mitotic recombination was detected in 38 (29.9%). Neither gene conversion nor chromosome loss was detected. These observations document the mechanisms responsible for gene loss in normal human cells in vivo, emphasize the importance of mitotic recombination, and indicate the similarity between mutational mechanisms in normal cells and in cancer cells.
authors.affiliation: Department of Haematology, Flinders Medical Centre, Bedford Park SA.
authors.forename: A A
authors.initials: AA
authors.lastname: Morley
authors.forename: S A
authors.initials: SA
authors.lastname: Grist
authors.forename: D R
authors.initials: DR
authors.lastname: Turner
authors.forename: A
authors.initials: A
authors.lastname: Kutlaca
authors.forename: G
authors.initials: G
authors.lastname: Bennett
mesh_terms: D002478:Cells, Cultured; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D006580:Genetic Carrier Screening; D005819:Genetic Markers / Q000032:analysis; D005982:Glutathione Transferase / Q000235:genetics; D015234:HLA-A Antigens / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D008938:Mitosis; D009154:Mutation; D011995:Recombination, Genetic
chemical_list: D005819:Genetic Markers; D015234:HLA-A Antigens; D005982:Glutathione Transferase