Functional Genomics in the Mouse: Phenotype-Based Mutagenesis Screens

Table 1.

Mutagenesis Statistics for Saturation Screens

Number Dominant Recessive Region-specific (300 deletions)
G0mice 29,338 3,000 3,000
Mice to generate 31,138 166,140 7,743,480
Mice to screen 29,338 134,160 3,870,000
(900,000)
Recovered mutations 75,000 75,000 75,000
Mice for mapping 7,500,000 7,500,000 0
 Total mice 7,531,138 7,666,140 7,743,480
  • Dominant screen: Six hundred mutagenenized males mated with 1,200 wild-type females can produce 29,338 F1progeny for a phenotypic screen (600 + 1200 + 29,338 = 31,138).

  • Recessive screen: Sixty mutagenenized males mated with 120 wild-type females can produce 3,000 F1 progeny; these 3,000 F1 progeny must be mated with 3,000 wild-type partners, and 25,800 of their progeny must be collected to obtain 4.3 daughters per family to ensure 95% chance that one of the daughters inherited any given mutation (60 + 120 + 3,000 + 3,000 + 25,800 = 31,980). Each of the 4.3 daughters would need to produce 10.4 offspring in matings with their father to have a 95% chance of producing an affected pup, for a total of 134,160 (3,000 × 4.3 × 4.3 × 10.4) mice to be screened. Overall, 166,140 mice would be required (134,160 × 31,980).

  • Region-specific mutagenesis: Sixty mutagenenized males mated with 120 wild-type females can produce 3,000 F1 progeny. These 3,000 progeny must be mated with 300 deletion-bearing mice (9 × 105 crosses). At least 4.3 progeny per cross that bear the deletion must be screened (3,870,000 of 7,740,000 total animals generated) to identify at least 1 affected animal per cross at 95% certainty, for a total of 7,743,480 animals (7,740,000 + 60 + 120 + 3,000). If all chromosomes are marked as in the scheme in Fig. 3B, only 900,000 animals would need to be screened.

This Article

  1. Genome Res. 8: 698-710

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