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Molecular analyses of in vivo hprt mutations in human T-lymphocytes: IV. Studies in newborns

Journal Article · · Environmental and Molecular Mutagenesis; (USA)

In order to characterize in vivo gene mutations that occur during fetal development, molecular analyses were undertaken of mutant 6-thioguanine resistant T-lymphocytes isolated from placental cord blood samples of 13 normal male newborns. These mutant T-cells were studied to define hypoxanthine-guanine phosphoribosyltransferase (hprt) gene structural alterations and to determine T-cell receptor (TCR) gene rearrangement patterns. Structural hprt alterations, as shown by Southern blot analyses, occurred in 85% of these mutant clones. These alterations consisted mostly of deletion of exons 2 and 3. These findings contrast with the 10-20% of gross structural alterations occurring randomly across the entire gene previously reported for T-cell mutants isolated from normal young adults. Iterative analyses of hprt structural alterations and TCR gene rearrangement patterns show that approximately one-third of the newborn derived mutants may have originated as pre- or intrathymic hprt mutations. This too contrasts with previous findings in adults where the background in vivo hprt mutations appeared to originate in postthymic T-lymphocytes.

OSTI ID:
6896780
Journal Information:
Environmental and Molecular Mutagenesis; (USA), Journal Name: Environmental and Molecular Mutagenesis; (USA) Vol. 14:4; ISSN 0893-6692; ISSN EMMUE
Country of Publication:
United States
Language:
English