Estimating the number of coding mutations in genotypic- and phenotypic-driven N-ethyl-N-nitrosourea (ENU) screens
Abstract
N-ethyl-N-nitrosourea (ENU) is a widely used mutagen in genotypic and phenotypic screens aimed at elucidating gene function. The high rate at which ENU induces point mutations raises the possibility that an observed phenotype may be to the result of another unidentified linked mutation. This article presents methods for estimating the probability of additional linked coding mutations (1) in a given region of DNA using both Poisson and Bayesian models and in (2) an F(1) animal exposed to ENU that has undergone b number of backcrosses. Applying these methods to the mouse data set of Quwailid et al., we estimate that the probability that a confounding mutation is linked to a cloned mutation when the candidate region is 5 Mb is very slim (p < 0.002). Where mutants are identified by genotypic methods, we show that backcrossing in the absence of marker-assisted selection is an inefficient means of eliminating linked confounding mutations.
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The chance of a second point mutation occurring in a coding region in this linked interval is extremely small (p = 0.0008, based on a mutation rate of 1 in 1.82 Mb).
“The chance of a second point mutation occurring in a coding region in this linked interval is extremely small (p = 0.0008, based on a mutation rate of 1 in 1.82 Mb) [15-17].”
From A genome-wide screen for modifiers of transgene variegation identifies genes with critical roles in development (2008) · cites this paper as [16]
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van Boxtel, R., & Cuppen, E. P. J. G. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-974-1_18 · Cited by 7 · see citing works
Rat Knockout and Mutant Models
Smits, B. M. G., Haag, J. D., Gould, M. N., & Cuppen, E. P. J. G. (2008) · Humana Press eBooks · doi:10.1007/978-1-59745-285-4_19 · Cited by 4 · see citing works
Target-Selected ENU Mutagenesis to Develop Cancer Models in the Rat
Smits, B. M. G., Cuppen, E. P. J. G., & Gould, M. N. (2011) · Springer eBooks · doi:10.1007/978-0-387-69805-2_6 · Cited by 1 · see citing works
Deconstructing Gene Function through ENU Mutagenesis
Acevedo‐Arozena, A., Ricketts, T., & Corrochano, S. (2010) · Wiley eBooks · doi:10.1002/9780470015902.a0022409
Deconstructing Gene Function through ENU Mutagenesis
Potter, P. K. (2018) · Wiley eBooks · doi:10.1002/9780470015902.a0022409.pub2
Deconstructing Gene Function through ENU Mutagenesis
Potter, P. K. (2019) · Wiley eBooks · doi:10.1002/9781405165518.a0022409.pub2
Mutations and Experimental Mutagenesis
Guénet, J., Benavides, F. J., Panthier, J., & Montagutelli, X. (2014) · Springer eBooks · doi:10.1007/978-3-662-44287-6_7
- Authors
- Keays, D. A., Clark, T. G., & Flint, J.
- Affiliations
- Centre for Human Genetics (GB)
- Imperial College London (GB)
- Corresponding author
- Keays, David A.
- ORCID
- Clark, Taane G.
- Venue
- Mammalian Genome
- Published
- 2006-03
- Volume
- 17
- Issue
- 3
- Pages
- 230-238
- ISSN
- 0938-8990 (ISSN-L)
- 1432-1777
- OpenAlex
- W4251534349
- Cited by
- 55
- References
- 41
- Citations by year
- 2019: 1 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 5
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Mammalian Genome (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Genetic and Mutation Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Keywords
- N-ethyl-N-nitrosourea mutagenesis, coding mutations, backcrossing, marker-assisted selection, Poisson model, Bayesian model, gene function, point mutations
- MeSH terms
- Animals, Codon, Ethylnitrosourea, Genetic Testing, Genotype, Mutagens, Mutation, Phenotype, Mutagenesis, Mice
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