Spontaneous mutation spectrum in the hprt gene in human lymphoblastoid TK6 cells

A spectrum of 100 mutations in the endogenous hprt gene of the human lymphoblastoid TK6 cell line is presented. The majority of the mutations originates in sequences outside the coding region of the gene. Large deletions are a major cause of inactivation of the hprt gene (57% of the mutants). Mutations in the splice sites that result in several forms of aberrantly spliced mRNA are relatively frequently recovered (16%) compared with mutants containing alterations in the coding region of the hprt gene (27%). The majority, but not all, of the splice mutants contain an alteration in the consensus sequences of the splice sites. A spectrum of mutations in the coding region of the hprt gene enlarged to a total of 42 mutants shows that basepair substitutions predominate (71%) and that small deletions and insertions are less frequently recovered. Basepair substitutions arise slightly more frequently at GC basepairs than at AT basepairs.