Mouse genetic and phenotypic resources for human genetics - PubMed (original) (raw)

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Mouse genetic and phenotypic resources for human genetics

Paul N Schofield et al. Hum Mutat. 2012 May.

Abstract

The use of model organisms to provide information on gene function has proved to be a powerful approach to our understanding of both human disease and fundamental mammalian biology. Large-scale community projects using mice, based on forward and reverse genetics, and now the pan-genomic phenotyping efforts of the International Mouse Phenotyping Consortium, are generating resources on an unprecedented scale, which will be extremely valuable to human genetics and medicine. We discuss the nature and availability of data, mice and embryonic stem cells from these large-scale programmes, the use of these resources to help prioritize and validate candidate genes in human genetic association studies, and how they can improve our understanding of the underlying pathobiology of human disease.

© 2012 Wiley Periodicals, Inc.

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Figures

Figure 1

Figure 1

Knockout strategies used by the IKMC. A. EUCOMM/KOMP-CSD knockout-first allele; B. KOMP-Regeneron null allele; C. NorCOMM promoter-driven targeting vector. Allele tm1a (D) contains an IRES:lacZ cassette and a floxed promoter-driven neo cassette inserted into the intron of the target gene knocking out gene function. Flp converts the tm1a allele to the conditional allele (tm1c), restoring gene function. Cre deletes the promoter-driven selection cassette and floxed exon of the tm1a allele to generate a lacZ-tagged allele (tm1b) or deletes the floxed exon of the tm1c allele to produce a frameshift mutation (tm1d).

Figure 2

Figure 2

Number of genes for which IKMC ES cells with a given allele type are available. (Redrawn from

http://www.knockoutmouse.org/

December 20. 2011)

Figure 3

Figure 3

Draft in vivo and post mortem phenotyping pipelines for the IMPC. Mandatory tests will be carried out by all of the mouse clinics, with some non-mandatory tests such as histopathology being carried out in only a few centres. The details, order and density of assays may change as discussions progress. Details can be found on

http://www.mousephenotype.org/workgroups/impc-phenotyping-work-group

.

References

    1. 1000 _genomes_consortium. A map of human genome variation from population-scale sequencing. Nature. 2010;467:1061–73. -PMC -PubMed
    1. Abbott A. Mouse project to find each gene’s role. Nature. 2010;465:410. -PubMed
    1. Acevedo-Arozena A, Wells S, Potter P, Kelly M, Cox RD, Brown SD. ENU mutagenesis, a way forward to understand gene function. Annu Rev Genomics Hum Genet. 2008;9:49–69. -PubMed
    1. Amberger J, Bocchini C, Hamosh A. A new face and new challenges for Online Mendelian Inheritance in Man (OMIM) Hum Mutat. 2011;32:564–7. -PubMed
    1. Austin CP, Battey JF, Bradley A, Bucan M, Capecchi M, Collins FS, Dove WF, Duyk G, Dymecki S, Eppig JT, et al. The knockout mouse project. Nat Genet. 2004;36:921–4. -PMC -PubMed

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