Spectrum of spontaneous HPRT mutations in TK6 human lymphoblasts

Abstract
The occurrence of deletions, coding sequence alterations, and intronic changes leading to aberrant splicing has been characterized among 33 spontaneous HPRT mutants in TK6 human lymphoblasts. Deletions detectable by multiplex PCR amplification accounted for 45% (15/33) of the mutant collection. Base substitutions represented 30% (10/33) of the total, and were predominated by changes at G:C base pairs. The remaining mutants were distributed among frameshifts (9%, 3/33), small deletions (6%, 2/33), and compound alterations (9%, 3/33). Five mutants (15%) demonstrated aberrant splicing of the hprt transcript. A cluster of 4 deletion/insertion events was identified in hprt exon 6. A nearly perfect 13 bp duplication differed from the original sequence only by an A:T to G:C transition, which was observed as a unique alteration in another HPRT mutant. A model involving correction of a mismatch in a secondary structure formed by the duplicated sequence may account for these results.