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Molecular mechanisms of spontaneous and induced loss of heterozygosity in human cells in vitro.

Publication ,  Journal Article
Li, CY; Yandell, DW; Little, JB
Published in: Somat Cell Mol Genet
January 1992

The human TK6 lymphoblast cell line is heteroallelic at the thymidine kinase (TK) locus, with one functional and one nonfunctional allele. Cells that have undergone loss of heterozygosity (LOH) at TK can be selected and cloned in an in vitro assay. In order to study the extent of LOH, we have analyzed a total of 166 thymidine kinase-deficient mutants that arose either spontaneously or following induction by X-ray or ethyl methane sulfonate (EMS) using DNA probes in and around the TK gene on chromosome 17. Two distinct groups of mutants with different doubling times were identified. Among slow-growth mutants, the predominant change for both spontaneous and induced mutants was LOH that generally extended through the entire TK gene to both proximal and distal markers on 17q. While the majority of both spontaneous and X-ray-induced normal-growth mutants showed LOH, this was considerably more localized in scale for X-ray-induced mutants, which rarely involved the distal marker. LOH was rare among EMS-induced normal-growth mutants. LOH was never observed with a 17p marker, indicating that nondisjunctional events were not involved in any of the mutant clones examined. Densitometric analysis of the LOH mutants indicated mitotic recombination was a likely mechanism in more than half the spontaneous LOH mutants in both groups, whereas most induced mutants appeared to arise from simple deletions.

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Published In

Somat Cell Mol Genet

DOI

ISSN

0740-7750

Publication Date

January 1992

Volume

18

Issue

1

Start / End Page

77 / 87

Location

United States

Related Subject Headings

  • Thymidine Kinase
  • Mutation
  • Lymphocytes
  • Humans
  • Heterozygote
  • Ethyl Methanesulfonate
  • Developmental Biology
  • Densitometry
  • Clone Cells
  • Chromosomes, Human, Pair 17
 

Citation

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Li, C. Y., Yandell, D. W., & Little, J. B. (1992). Molecular mechanisms of spontaneous and induced loss of heterozygosity in human cells in vitro. Somat Cell Mol Genet, 18(1), 77–87. https://doi.org/10.1007/BF01233450
Li, C. Y., D. W. Yandell, and J. B. Little. “Molecular mechanisms of spontaneous and induced loss of heterozygosity in human cells in vitro.Somat Cell Mol Genet 18, no. 1 (January 1992): 77–87. https://doi.org/10.1007/BF01233450.
Li CY, Yandell DW, Little JB. Molecular mechanisms of spontaneous and induced loss of heterozygosity in human cells in vitro. Somat Cell Mol Genet. 1992 Jan;18(1):77–87.
Li, C. Y., et al. “Molecular mechanisms of spontaneous and induced loss of heterozygosity in human cells in vitro.Somat Cell Mol Genet, vol. 18, no. 1, Jan. 1992, pp. 77–87. Pubmed, doi:10.1007/BF01233450.
Li CY, Yandell DW, Little JB. Molecular mechanisms of spontaneous and induced loss of heterozygosity in human cells in vitro. Somat Cell Mol Genet. 1992 Jan;18(1):77–87.

Published In

Somat Cell Mol Genet

DOI

ISSN

0740-7750

Publication Date

January 1992

Volume

18

Issue

1

Start / End Page

77 / 87

Location

United States

Related Subject Headings

  • Thymidine Kinase
  • Mutation
  • Lymphocytes
  • Humans
  • Heterozygote
  • Ethyl Methanesulfonate
  • Developmental Biology
  • Densitometry
  • Clone Cells
  • Chromosomes, Human, Pair 17