Skip to main content

Advertisement

SpringerLink
Log in

From ENU mutagenesis to population genetics

  • Published:
Mammalian Genome Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • Barbaric I, Wells S, Russ A, Dear TN (2007) Spectrum of ENU-induced mutations in phenotype-driven and gene-driven screens in the mouse. Environ Mol Mutagen 48:124–142

    Article  PubMed  CAS  Google Scholar 

  • Blagosklonny MV (2000) p53 from complexity to simplicity: mutant p53 stabilization, gain-of-function, and dominant-negative effect. FASEB J 14:1901–1907

    Article  PubMed  CAS  Google Scholar 

  • Charlesworth J, Eyre-Walker A (2007) The other side of the nearly neutral theory, evidence of slightly advantageous back-mutations. Proc Natl Acad Sci U S A 104:16992–16997

    Article  PubMed  CAS  Google Scholar 

  • Clark AT, Goldwitz D, Takahashi JS, Vitatema MH, Siepka SM et al (2004) Implementing large-scale ENU mutagenesis screens in North America. Genetica 122:51–64

    Article  PubMed  CAS  Google Scholar 

  • Cook MC, Vinuesa CG, Goodnow CC (2006) ENU-mutagenesis: insight into immune function and pathology. Curr Opin Immunol 18:627–633

    Article  PubMed  CAS  Google Scholar 

  • Cook MN, Dunning JP, Wiley RG, Chesler EJ, Johnson DK et al (2007) Neurobehavioral mutants identified in an ENU-mutagenesis project. Mamm Genome 18:559–572

    Article  PubMed  Google Scholar 

  • Daiger SP, Bowne SJ, Sullivan LS (2007) Perspective on genes and mutations causing retinitis pigmentosa. Arch Ophthalmol 125:151–158

    Article  PubMed  CAS  Google Scholar 

  • Eades-Perner AM, Gathmann B, Knerr V, Guzman D, Veit D et al (2007) The European internet-based patient and research database for primary immunodeficiencies: results 2004–06. Clin Exp Immunol 147:306–312

    Article  PubMed  Google Scholar 

  • Edmands S (2007) Between a rock and a hard place: evaluating the relative risks of inbreeding and outbreeding for conservation and management. Mol Ecol 16:463–475

    Article  PubMed  Google Scholar 

  • Eyre-Walker A, Keightley PD (2007) The distribution of fitness effects of new mutations. Nat Rev Genet 8:610–618

    Article  PubMed  CAS  Google Scholar 

  • Falconer DS (1989) Introduction to Quantitative Genetics, 3rd edn. Longmann, London

    Google Scholar 

  • Furney SJ, Alba MM, Lopez-Bigas N (2006) Differences in the evolutionary history of disease genes affected by dominant or recessive mutations. BMC Genomics 7:165

    Article  PubMed  CAS  Google Scholar 

  • Godinho SI, Nolan PM (2006) The role of mutagenesis in defining genes in behaviour. Eur J Hum Genet 14:651–659

    Article  PubMed  CAS  Google Scholar 

  • Hawks J, Hunley K, Lee SH, Wolpoff M (2000) Population bottlenecks and Pleistocene human evolution. Mol Biol Evol 17:2–22

    PubMed  CAS  Google Scholar 

  • Hoyne GF, Goodnow CC (2006) The use of genomewide ENU mutagenesis screens to unravel complex mammalian traits: identifying genes that regulate organ-specific and systemic autoimmunity. Immunol Rev 210:27–39

    Article  PubMed  CAS  Google Scholar 

  • Hrabé de Angelis MH, Flaswinkel H, Fuchs H, Rathkolb B, Soewarto D et al (2000) Genome-wide, large-scale production of mutant mice by ENU mutagenesis. Nat Genet 25:444–447

    Article  CAS  Google Scholar 

  • Hurst LD, Randerson JP (2000) Dosage, deletions and dominance: simple models of the evolution of gene expression. J Theor Biol 205:641–647

    Article  PubMed  CAS  Google Scholar 

  • Jablonski MM, Wang X, Lu L, Miller DR, Rinchik EM et al (2005) The Tennessee Mouse Genome Consortium: identification of ocular mutants. Vis Neurosci 22:595–604

    PubMed  Google Scholar 

  • Jimenez-Sanchez G, Childs B, Valle D (2001) Human disease genes. Nature 409:853–855

    Article  PubMed  CAS  Google Scholar 

  • Johnston JA, Ward CL, Kopito RR (1998) Aggresomes: a cellular response to misfolded proteins. J Cell Biol 143:1883–1898

    Article  PubMed  CAS  Google Scholar 

  • Justice MJ, Noveroske JK, Weber JS, Zheng B, Bradley A (1999) Mouse ENU mutagenesis. Hum Mol Genet 8:1955–1963

    Article  PubMed  CAS  Google Scholar 

  • Kafri R, Levy M, Pilpel Y (2006) The regulatory utilization of genetic redundancy through responsive backup circuits. Proc Natl Acad Sci U S A 103:11653–11658

    Article  PubMed  CAS  Google Scholar 

  • Keightley PD (1994) The distribution of mutation effects on viability in Drosophila melanogaster. Genetics 138:1315–1322

    PubMed  CAS  Google Scholar 

  • Kondrashov FA, Koonin EV (2004) A common framework for understanding the origin of genetic dominance and evolutionary fates of gene duplications. Trends Genet 20:287–290

    Article  PubMed  CAS  Google Scholar 

  • Lopez-Bigas N, Blencowe BJ, Ouzounis CA (2006) Highly consistent patterns for inherited human diseases at the molecular level. Bioinformatics 22:269–277

    Article  PubMed  CAS  Google Scholar 

  • Lynch M, Conery JS (2000) The evolutionary fate and consequences of duplicate genes. Science 290:1151–1155

    Article  PubMed  CAS  Google Scholar 

  • Masuya H, Nakai Y, Motegi H, Niinaya N, Kida Y et al (2004) Development and implementation of a database system to manage a large-scale mouse ENU-mutagenesis program. Mamm Genome 15:404–411

    Article  PubMed  CAS  Google Scholar 

  • Mendes HF, van der Spuy J, Chapple JP, Cheetham ME (2005) Mechanisms of cell death in rhodopsin retinitis pigmentosa: implications for therapy. Trends Mol Med 11:177–185

    Article  PubMed  CAS  Google Scholar 

  • Mitchell-Olds T, Willis JH, Goldstein DB (2007) Which evolutionary processes influence natural genetic variation for phenotypic traits? Nat Rev Genet 8:845–856

    Article  PubMed  CAS  Google Scholar 

  • Nielsen R, Bustamante C, Clarke AG, Glanowski S, Sackton TB et al (2005) A scan for positively selected genes in the genomes of humans and chimpanzees. PLoS Biol 3:e170

    Article  PubMed  CAS  Google Scholar 

  • Nielsen R, Hellmann I, Hubisz M, Bustamante C, Clark AG (2007) Recent and ongoing selection in the human genome. Nat Rev Genet 8:857–868

    Article  PubMed  CAS  Google Scholar 

  • Nolan PM, Peters J, Strivens M, Rogers D, Hagan J et al (2000) A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse. Nat Genet 25:440–443

    Article  PubMed  CAS  Google Scholar 

  • Pinto LH, Vitatema MH, Siepka SM, Shimomura K, Lumayag S et al (2004) Results from screening over 9000 mutation-bearing mice for defects in the electroretinogram and appearance of the fundus. Vision Res 44:3335–3345

    Article  PubMed  CAS  Google Scholar 

  • Reijmers LG, Coats JK, Pletcher MT, Wiltshire T, Tarantino LM et al (2006) A mutant mouse with a highly specific contextual fear-conditioning deficit found in an N-ethyl-N-nitrosourea (ENU) mutagenesis screen. Learn Mem 13:143–149

    Article  PubMed  CAS  Google Scholar 

  • Seidman JG, Seidman C (2002) Transcription factor haploinsufficiency: when half a loaf is not enough. J Clin Invest 109:451–455

    PubMed  CAS  Google Scholar 

  • Takahasi KR, Sakuraba Y, Gondo Y (2007) Mutational pattern and frequency of induced nucleotide changes in mouse ENU mutagenesis. BMC Mol Biol 8:52

    Article  PubMed  CAS  Google Scholar 

  • The Mouse Phenotype Database Integration Consortium (2007) Integration of mouse phenome data resources. Mamm Genome 18:157–163

    Article  Google Scholar 

  • Tirosh I, Bilu Y, Barkai N (2007) Comparative biology: beyond sequence analysis. Curr Opin Biotechnol 18:371–377

    Article  PubMed  CAS  Google Scholar 

  • Vihinen M, Arredondo-Vega FX, Casanova JL, Etzioni A, Giliani S et al (2001) Primary immunodeficiency mutation databases. Adv Genet 43:103–188

    Article  PubMed  CAS  Google Scholar 

  • Williamson SH, Hernandez R, Fledel-Alon A, Zhu L, Nielsen R et al (2005) Simultaneous inference of selection and population growth from patterns of variation in the human genome. Proc Natl Acad Sci U S A 102:7882–7887

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The authors thank Shomi Bhattacharya for help in preparing this commentary.

Author information

Authors and Affiliations

  1. Institute of Ophthalmology, University College London, London, UK

    N. Avrion Mitchison

  2. Institute of Genetics, School of Biology, University of Nottingham, Nottingham, UK

    Bryan Clarke

Authors
  1. N. Avrion Mitchison
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bryan Clarke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. Avrion Mitchison.

Appendix

Appendix

The relationship between mutagenesis and population genetics from the present perspective can be summarized thus:

$$ {\text{(1-Pdom}}^{{{\text{OMIM}}}} {\text{):(1-Pdom}}^{{{\text{ENU}}}} {\text{)::Ka:Ks}} $$

where 1-PdomOMIM denotes the proportion of recessively inherited disease as referenced in the OMIM (Online Mendelian Inheritance In Man) database, not the proportion of dominant mutations, and 1-PdomENU is the frequency of recessive mutations obtained by ENU mutagenesis in mouse (i.e., the G3/G1 ratio). Ka and Ks are the frequencies, respectively, of nonsynonymous and synonymous nucleotide substitutions observed in the comparable part of human the population. The “::” sign signifies similarity of function but not numerical equality and should be read as “as.” On either side a parameter that is subject to natural selection is compared with a supposedly unselected control.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mitchison, N.A., Clarke, B. From ENU mutagenesis to population genetics. Mamm Genome 19, 221–225 (2008). https://doi.org/10.1007/s00335-008-9104-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00335-008-9104-2

Keywords

Search

Navigation