Genetic studies on human lymphoblastoid cell lines: isozyme and cytogenetic heterogeneity in a cell line, with evidence for localization of the Pep A locus in man.

One hundred and thirty-three clones (60 mutagen treated, 73 controls) of the human male lymphoblastoid cell line F 137 have been examined for the electrophoretic pattern of more than 30 enzymes. In nine instances there was loss of activity of one allele of an X-linked or heterozygous autosomal locus. Seven of these involved the Pep A locus, and in every case the change was from the Pep A 2-1 phenotype to Pep A 2. Cytogenetic analysis of the parent line revealed a number of variants on the modal karyotype. On cloning, there appeared to be some selection for survival of non-modal cells. The proportions of the cytogenetically distinct populations within the bulk culture varied over a period of many months. There was a strong correlation in individual clones between loss of activity of the product of the Pep A1 allele and the presence in the cells of a 9/18 translocation. In addition there was one clone of phenotype Pep A 2 with a deletion of part of the long arm of chromosome 18. The data confirms the assignment of the Pep A structural locus to the distal half of the long arm of chromosome 18 and localizes it with some precision to the qter region. The Pep A 2 phenotype of the clones containing the 9/18 translocation could be the result of a small deletion eliminating the Pep A1 allele but not large enough to be detected cytogenetically. Alternatively inactivation of the Pep A1 allele may have occurred as a position effect resulting from the close association of heterochromatin from the centromere of 9 with the qter region of 18.