Software for the analysis of mutations at the human hprt gene

Abstract

Mutations at the human hypoxanthine-guanine phosphoribosyl transferase gene ( hprt) are currently of great interest because mutations at this locus are being used as a biomonitor of human mutagenic exposure. Not only can somatic hprt mutants arising in vivo in humans be recovered and sequenced, but there is also a considerable body of information about the in vitro mutational spectra of different carcinogens at this locus. Previously, we reported the creation of a computerized database containing DNA-sequence information on human hprt mutants (Cariello et al. (1992) Environ. Mol. Mutagen., 20, 81–83). In the present manuscript, software for the analysis of mutations in the hprt database is described. Numerous routines have been developed for the analysis of single-base substitutions, including programs to (i) determine if two mutational spectra are different, (ii) display the number of mutations and mutable sites in each exon, (iii) determine if mutations show a DNA-strand bias, (iv) determine the frequency of transitions and transversions, (v) display the number and kind of mutations observed at each base in the coding region, (vi) perform nearest-neighbor analysis and (vii) display mutable amino acids in the hprt protein. The software runs only on IBM-compatible machines with MS-DOS. The software and hprt database is freely available via the INTERNET using remote file-transfer protocol. These programs simplify the analysis of the rapidly increasing information about hprt mutation. The programs permit the facile comparison between in vitro and in vivo data, as well as the identification of mutational patterns that may be of importance to experimenters using hprt as a biomonitor and of importance to researchers studying mechanisms of mutation.