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Related Experiment Videos

Functional genomics in the mouse: phenotype-based mutagenesis screens

J Schimenti1, M Bucan

  • 1The Jackson Laboratory, Bar Harbor, Maine 04609 USA.

Genome Research
|August 1, 1998
PubMed
Summary

Mouse mutagenesis screens are crucial for understanding gene function and human genome parallels. Region-specific screens using chemical mutagenesis and deletion complexes offer a feasible approach for rapid functional analysis.

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Genome research·2001

Area of Science:

  • Genomics and Genetics
  • Functional Genomics
  • Mammalian Genetics

Background:

  • Genome sequencing projects, including the human genome, are advancing rapidly.
  • Elucidating the functional content of the human genome requires robust model systems.
  • The mouse serves as a critical model organism for functional genomic studies.

Purpose of the Study:

  • To review and compare genetic approaches for gene function analysis in mice.
  • To highlight the utility of phenotype-based mutagenesis screens for generating mutations.
  • To propose feasible strategies for systematic functional analysis of the mouse genome.

Main Methods:

  • Comparison of classical genetic approaches with large-scale and region-specific mutagenesis screens.
  • Utilizing high-efficiency chemical mutagenesis in conjunction with deletion complexes generated by embryonic stem (ES) cells.
  • Rapid creation and analysis of deletion complexes for mapping chemically-induced mutations.

Main Results:

  • Region-specific saturation screens are a practical alternative to impractical genome-wide screens for identifying gene loci.
  • Combining chemical mutagenesis with ES cell-derived deletion complexes enables efficient mutation generation and analysis within two generations.
  • This approach facilitates the systematic functional analysis of the mouse genome and its human orthologs.

Conclusions:

  • Region-specific mutagenesis screens in mice are a powerful tool for functional genome analysis.
  • The described methods accelerate the identification and characterization of gene functions.
  • Sequencing efforts should prioritize chromosomal regions targeted for extensive mutagenesis screens.

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