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Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
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Rapid identification of major-effect genes using the collaborative cross.

Ramesh Ram1, Munish Mehta1, Lois Balmer1

  • 1Centre for Diabetes Research, Harry Perkins Institute of Medical Research, Nedlands 6009, WA, Australia Centre of Medical Research, University of Western Australia, Nedlands 6009, WA, Australia.

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|September 20, 2014
PubMed
Summary

The Collaborative Cross (CC) resource enables rapid gene mapping. This study successfully identified causative genes for five coat color traits in mice, demonstrating its power for genetic research.

Keywords:
Collaborative Cross (CC)MPPMultiparent Advanced Generation Inter-Cross (MAGIC)Multiparental populationsThe Collaborative Crosscomplex traitsgene mappinggenetic analysesquantitative trait locus mapping

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Area of Science:

  • Genetics
  • Genomics
  • Mammalian Genetics

Background:

  • The Collaborative Cross (CC) is a powerful genetic resource comprising hundreds of recombinant inbred mouse lines.
  • These lines are derived from eight diverse founder strains, enabling high-resolution genetic mapping.
  • The CC has been in production for a decade and is now ready for broad application in mapping projects.

Purpose of the Study:

  • To demonstrate the utility of the Collaborative Cross for rapid identification of major-effect genes.
  • To validate the CC resource for gene mapping studies using well-characterized coat color traits.
  • To develop and test analytical pipelines for mapping complex genetic architectures within the CC.

Main Methods:

  • Phenotypic assessment of six coat color traits across 110 CC lines.
  • Development of a modified mapping pipeline tailored for the CC's complex genetic structure.
  • Integration of CC line data with founder genome sequences for high-resolution mapping.

Main Results:

  • Successfully mapped and identified causative genes for five coat color traits.
  • Demonstrated the CC's capability for precise gene localization.
  • Developed strategies for detecting gene interactions, including testing joint effects of three loci.

Conclusions:

  • The Collaborative Cross is a highly effective resource for rapid gene mapping.
  • The CC facilitates the identification of both qualitative and quantitative trait loci.
  • This study provides confidence in the CC's application to complex trait analysis in genetics research.