Mutation rate and predicted phenotypic target sizes in ethylnitrosourea-treated mice.
Chemical mutagenesis of the mouse is ongoing in several centers around the world, with varying estimates of mutation rate and number of sites mutable to phenotype. To address these questions, we sequenced approximately 9.6 Mb of DNA from G1 progeny of ethylnitrosourea-treated mice in a large, broad-spectrum screen. We identified 10 mutations at eight unique sites, including six nonsynonymous coding substitutions. This calibrates the nucleotide mutation rate for two mutagenesis centers, implies significance criteria for positional cloning efforts, and provides working estimates of effective genetic target sizes for selected phenotypes.
Concepcion
Dorothy
D
University of California-San Diego School of Medicine, San Diego, California 92093-0644, USA.
Seburn
Kevin L
KL
Wen
Gen
G
Frankel
Wayne N
WN
Hamilton
Bruce A
BA
D000477:Alkylating Agents / Q000494:pharmacology*; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D005038:Ethylnitrosourea / Q000494:pharmacology*; D005260:Female; D005820:Genetic Testing; D006720:Homozygote; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D010802:Phylogeny; D011237:Predictive Value of Tests; D017386:Sequence Homology, Amino Acid
D000477:Alkylating Agents; D005038:Ethylnitrosourea