Segregation of recessive phenotypes in somatic cell hybrids role of mitotic recombination, gene inactivation, and chromosome nondisjunction
Somatic cell hybrids heterozygous at the emetine resistance locus (emt/sup r//emt/sup +/) or the chromate resistance locus (chr/sup r//chr/sup +/) are known to segregate the recessive drug resistance phenotype at high frequency. The authors have examined mechanisms of segregation in Chinese hamster cell hybrids heterozygous at these two loci, both of which map to the long arm of Chinese hamster chromosome 2. To allow the fate of chromosomal arms through the segregation process, our hybrids were also heterozygous at the mtx (methotrexate resistance) locus on the short arm of chromosome 2 and carried cytogenetically marked chromosomes with either a short-arm deletion 2p/sup -/) or a long-arm addition (2q/sup +/). Karotype and phenotype analysis of emetine- or chromate-resistant segregants from such hybrids allowed us to distinguish four potential segregation mechanisms: (i) loss of the emt/sup +/ - or chr/sup +/-bearing chromosome; (ii) mitotic recombination between the centromere and the emt or chr loci giving rise to homozygous resistant segregants; (iii) inactivation of the emt/sup +/ or chr/sup +/ alleles; and (iv) loss of the emt/sup +/ - or chr/sup +/-bearing chromosome with duplication of the homologous chromosome carrying the emt/sup r/ or chr/sup r/ allele. Of 48 independent segregants examined, only 9 (20%) arose by simple chromosome loss. Two segregants (4%) were consistent with a gene inactivation mechanism, but because of their rarity, other mechanisms such as mutation or submicroscopic deletion could not be excluded. Twenty-one segregants (44%) arose by either mitotic recombination or chromosome loss and duplication; the two mechanisms were not distinguishable in that experiment. Finally, in hybrids allowing these two mechanisms to be distinguished, 15 segregants (31%) arose by chromosome loss and duplication, and none arose by mitotic recombination.
- Research Organization:
- Dept. of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461
- OSTI ID:
- 5996120
- Journal Information:
- Mol. Cell. Biol.; (United States), Vol. 1:4
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ANTIBIOTICS
CHEMISTRY
SOMATIC MUTATIONS
FREQUENCY MEASUREMENT
BIOLOGICAL MARKERS
CHO CELLS
CHROMATES
CHROMOSOMAL ABERRATIONS
CHROMOSOME LOSSES
CHROMOSOMES
GENE RECOMBINATION
GENE REPRESSORS
GENETIC MAPPING
HYBRIDIZATION
KARYOTYPE
METHOTREXATE
MITOSIS
NON-DISJUNCTION
PHENOTYPE
SENSITIVITY
SEPARATION PROCESSES
ANIMAL CELLS
ANTI-INFECTIVE AGENTS
ANTIMETABOLITES
CELL DIVISION
CHROMIUM COMPOUNDS
DRUGS
LOSSES
MAPPING
MUTATIONS
NUCLEOPROTEINS
ORGANIC COMPOUNDS
OXYGEN COMPOUNDS
PROTEINS
TRANSITION ELEMENT COMPOUNDS
550400* - Genetics
550200 - Biochemistry