Estimating the number of coding mutations in genotypic- and phenotypic-driven N-ethyl-N-nitrosourea (ENU) screens.

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...

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Main Authors: Keays, D, Clark, T, Flint, J
Format: Journal article
Language:English
Published: 2006
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author Keays, D
Clark, T
Flint, J
author_facet Keays, D
Clark, T
Flint, J
author_sort Keays, D
collection OXFORD
description 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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spelling oxford-uuid:128ff8dc-d0d7-40a7-a0d3-598a0207d4b02022-03-26T10:08:43ZEstimating the number of coding mutations in genotypic- and phenotypic-driven N-ethyl-N-nitrosourea (ENU) screens.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:128ff8dc-d0d7-40a7-a0d3-598a0207d4b0EnglishSymplectic Elements at Oxford2006Keays, DClark, TFlint, JN-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.
spellingShingle Keays, D
Clark, T
Flint, J
Estimating the number of coding mutations in genotypic- and phenotypic-driven N-ethyl-N-nitrosourea (ENU) screens.
title Estimating the number of coding mutations in genotypic- and phenotypic-driven N-ethyl-N-nitrosourea (ENU) screens.
title_full Estimating the number of coding mutations in genotypic- and phenotypic-driven N-ethyl-N-nitrosourea (ENU) screens.
title_fullStr Estimating the number of coding mutations in genotypic- and phenotypic-driven N-ethyl-N-nitrosourea (ENU) screens.
title_full_unstemmed Estimating the number of coding mutations in genotypic- and phenotypic-driven N-ethyl-N-nitrosourea (ENU) screens.
title_short Estimating the number of coding mutations in genotypic- and phenotypic-driven N-ethyl-N-nitrosourea (ENU) screens.
title_sort estimating the number of coding mutations in genotypic and phenotypic driven n ethyl n nitrosourea enu screens
work_keys_str_mv AT keaysd estimatingthenumberofcodingmutationsingenotypicandphenotypicdrivennethylnnitrosoureaenuscreens
AT clarkt estimatingthenumberofcodingmutationsingenotypicandphenotypicdrivennethylnnitrosoureaenuscreens
AT flintj estimatingthenumberofcodingmutationsingenotypicandphenotypicdrivennethylnnitrosoureaenuscreens