Mitotic recombination is the predominant cause of in vivo loss of heterozygosity in T lymphocytes of APRT heterozygotes
- Indiana Univ. School of Medicine, Indianapolis, IN (United States); and others
Loss of heterozygosity (LOH) has been demonstrated to play an important role in carcinogenesis. We have used the APRT gene in vivo as a model to study mechanisms of LOH. Analysis of polymorphic microsatellite repeats flanking APRT indicated that approximately 70% of 2,6-diaminopurine resistant T lymphocyte clones selected from the peripheral blood of APRT heterozygotes were caused by LOH spanning APRT. We performed molecular cytogenetic analysis of 10 T lymphocyte clones isolated from a male APRT heterozygote, each with a differently sized region of LOH. Karyotype analysis of 8 clones with LOH for relatively large regions (e.g., from 16q24.3 to 16q12.1), that would be detectable if caused by deletion, revealed two normal chromosomes 16, indicating that LOH was probably caused by mitotic recombination. FISH of two clones with small regions of LOH (e.g., within 16q24.3), using a cosmid containing APRT as the probe, showed that LOH was caused by mitotic recombination (both chromosomes 16 hybridized) in one, and deletion (only one chromosome 16 hybridized) in the other. Thus, 9 out of 10 in vivo LOH events spanning APRT were caused by mitotic recombination in the T lymphocytes and one involved a submicroscopic interstitial deletion.
- OSTI ID:
- 133755
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0487
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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