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Faculty Articles
PubMed Identifier
2491018
Title
Gene inactivation as a mechanism for the expression of recessive phenotypes.
ISBN or ISSN
0002-9297
Publication Title
American journal of human genetics
Volume
45
Issue
4
Publication Date / Copyright Date
10-1-1989
First Page
619
Last Page
634
Abstract
A series of Chinese hamster ovary cell hybrids were constructed which were heterozygous at the emtB and chr loci. These loci encode two recessive drug-resistance genes (emetine resistance and chromate resistance, respectively) located on a structurally hemizygous region on the long arm of chromosome 2. These heterozygous hybrids therefore exhibit wild-type sensitivity to both emetine and chromate. Drug-resistant variants were then selected in medium containing either emetine or chromate, and the mechanism of reexpression of the recessive drug-resistant allele was determined by karyotypic analysis of the resultant colonies. In previous studies at these loci we have determined that segregation of the recessive phenotype occurs primarily by (1) the loss of the chromosome 2 carrying the wild-type, drug-sensitive, allele, (2) deletion of the long arm of chromosome 2, or (3) loss of one chromosome 2 followed by duplication of the remaining homologue. However, a small proportion of segregants have also been detected which may have arisen by the mechanisms of de novo gene inactivation or mutation. In this report, hybrids are described which were constructed to allow selection for the retention of the chromosome carrying the wild-type allele and which therefore optimize isolation of these rare segregants. We demonstrate by karyotypic analysis, mutation frequency analysis, and microcell-mediated chromosome transfer that these rare segregants occur primarily by gene inactivation. We also demonstrate a dramatic increase in the proportion of segregants occurring by gene inactivation in two of these hybrids as compared with those previously reported, indicating that this mechanism may be an important mode of phenotype segregation in diploid cells and, therefore, in the development of cancers--such as the childhood tumors retinoblastoma and Wilms tumor--resulting from recessive alleles
Disciplines
Medical Specialties | Medicine and Health Sciences | Osteopathic Medicine and Osteopathy
Keywords
Animals, Cell Line, Chromosomes, Human, Pair 2, Cricetinae, Cricetulus, Ethyl Methanesulfonate, Female, Gene Expression, Genes, Recessive, Genetic Techniques, Humans, Hybrid Cells, Karyotyping, Mutagenesis, Ovary, Phenotype
NSUWorks Citation
Grant, S G.; Campbell, C E; Duff, C; Toth, S L.; and Worton, R G., "Gene inactivation as a mechanism for the expression of recessive phenotypes." (1989). Faculty Articles. 1529.
https://nsuworks.nova.edu/hpd_com_faculty_articles/1529