Mutational specificity: Mutation frequencies but not mutant frequencies in Big Blue® mice fit a Poisson distribution

✍ Scribed by Hiroshi Nishino; Daniel J. Schaid; Victoria L. Buettner; Jan Haavik; Steve S. Sommer

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 319 KB
• Volume: 28
• Category: Article
• ISSN: 0893-6692
• DOI: 10.1002/(sici)1098-2280(1996)28:4<414::aid-em16>3.0.co;2-i

✦ Synopsis

Transgenic mutation assays generally use mutant frequencies to estimate mutation frequencies but the degree to which clonal expansion inflates mutant frequencies i s largely unknown. Mutant frequency is defined as the fraction of cells carrying mutations in the gene of interest and, according to the stondard Big Blue" protocol, is determined by dividing the number of mutant plaques by the total number of plaques screened. Mutation frequency is determined as the fraction of cells carrying definitely independent mutations and therefore requires correction for clonal expansion. Mutant and mutation frequencies were determined for brain, thymus and male germ cells of four mice from two age groups (3versus 1 O-month old). The mutant frequency in thymus differed significantly between 3and 10month old mice (P < 0.05). By sequencing all mutants, the mutation frequency (i.e., corrected for jackpot mutations) in thymus was determined and was not significantly different between 3and 10month old mice. Mutant frequency does not fit a Poisson distribution, but mutation frequency corrected for jackpot mutations is substantially less variable and does fit a Poisson distribution.