Mutation rate and predicted phenotypic target sizes in ethylnitrosourea-treated mice

被引:68
作者
Concepcion, D
Seburn, KL
Wen, G
Frankel, WN
Hamilton, BA
机构
[1] Univ Calif San Diego, Sch Med, Palade Labs Cellular & Mol Med, La Jolla, CA 92093 USA
[2] Jackson Lab, Bar Harbor, ME 04609 USA
关键词
D O I
10.1534/genetics.104.029843
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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 similar to9.6 Mb of DNA from G(1) 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.
引用
收藏
页码:953 / 959
页数:7
相关论文
共 23 条
[1]   Sequence-based analysis of mutagenized mice [J].
Beier, DR .
MAMMALIAN GENOME, 2000, 11 (07) :594-597
[2]   Genotype-based screen for ENU-induced mutations in mouse embryonic stem cells [J].
Chen, YJ ;
Yee, D ;
Dains, K ;
Chatterjee, A ;
Cavalcoli, J ;
Schneider, E ;
Om, J ;
Woychik, RP ;
Magnuson, T .
NATURE GENETICS, 2000, 24 (03) :314-317
[3]   A gene-driven approach to the identification of ENU mutants in the mouse [J].
Coghill, EL ;
Hugill, A ;
Parkinson, N ;
Davison, C ;
Glenister, P ;
Clements, S ;
Hunter, J ;
Cox, RD ;
Brown, SDM .
NATURE GENETICS, 2002, 30 (03) :255-256
[4]   Base-calling of automated sequencer traces using phred.: II.: Error probabilities [J].
Ewing, B ;
Green, P .
GENOME RESEARCH, 1998, 8 (03) :186-194
[5]   Base-calling of automated sequencer traces using phred.: I.: Accuracy assessment [J].
Ewing, B ;
Hillier, L ;
Wendl, MC ;
Green, P .
GENOME RESEARCH, 1998, 8 (03) :175-185
[6]   Consed: A graphical tool for sequence finishing [J].
Gordon, D ;
Abajian, C ;
Green, P .
GENOME RESEARCH, 1998, 8 (03) :195-202
[7]   New approaches to understanding p53 gene tumor mutation spectra [J].
Hollstein, M ;
Hergenhahn, M ;
Yang, Q ;
Bartsch, H ;
Wang, ZQ ;
Hainaut, P .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 1999, 431 (02) :199-209
[8]   SOME RECENT STUDIES BEARING ON THE ONE GENE-ONE ENZYME HYPOTHESIS [J].
HOROWITZ, NH ;
LEUPOLD, U .
COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY, 1951, 16 :65-74
[9]   Effects of ENU dosage on mouse strains [J].
Justice, MJ ;
Carpenter, DA ;
Favor, J ;
Neuhauser-Klaus, A ;
de Angelis, MH ;
Soewarto, D ;
Moser, A ;
Cordes, S ;
Miller, D ;
Chapman, V ;
Weber, JS ;
Rinchik, EM ;
Hunsicker, PR ;
Russell, WL ;
Bode, VC .
MAMMALIAN GENOME, 2000, 11 (07) :484-488
[10]   Functional genetic analysis of mouse chromosome 11 [J].
Kile, BT ;
Hentges, KE ;
Clark, AT ;
Nakamura, H ;
Salinger, AP ;
Liu, B ;
Box, N ;
Stockton, DW ;
Johnson, RL ;
Behringer, RR ;
Bradley, A ;
Justice, MJ .
NATURE, 2003, 425 (6953) :81-86