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In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.

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The Diversity Outbred mouse population.

Gary A Churchill1, Daniel M Gatti, Steven C Munger

  • 1The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA. Gary.Churchill@jax.org

Mammalian Genome : Official Journal of the International Mammalian Genome Society
|August 16, 2012
PubMed
Summary
This summary is machine-generated.

The Diversity Outbred (DO) mouse population offers a powerful genetic resource for broad phenotype research. Its genetic diversity aids in identifying robust QTL mapping results applicable to diverse populations.

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Area of Science:

  • Genetics and Genomics
  • Animal Models
  • Quantitative Trait Loci (QTL) Mapping

Background:

  • The Diversity Outbred (DO) mouse population is a genetically heterogeneous stock derived from eight founder strains, sharing founders with the Collaborative Cross (CC) inbred strains.
  • DO mice exhibit a wide range of phenotypes due to natural heterozygosity, which also confers robustness and good breeding performance.
  • Genetic mapping in the DO population presents unique challenges and opportunities compared to traditional crosses.

Purpose of the Study:

  • To highlight the advantages and methodologies for genetic mapping in the genetically heterogeneous DO mouse population.
  • To discuss the utility of DO mice for identifying quantitative trait loci (QTL) and understanding genetic architecture.
  • To emphasize the DO's potential for generalizing findings to broader, genetically diverse populations.

Main Methods:

  • Utilizing specialized algorithms for haplotype reconstruction from high-density SNP array data, accommodating 36 possible diplotypes from eight founder haplotypes.
  • Incorporating population structure analysis specific to the DO population in QTL mapping.
  • Estimating allele effects of founder haplotypes to reduce candidate loci and distinguish pleiotropy from chance QTL colocation.

Main Results:

  • DO mice offer unique allele effect information not available in two-parent crosses, significantly reducing the number of candidate loci.
  • QTL mapping in DO mice can differentiate between pleiotropy and chance colocation, supporting causality in expression QTL studies.
  • Recommended sample sizes for DO QTL mapping studies range from 200-800 mice, larger than for traditional crosses.

Conclusions:

  • The DO population is a valuable resource for genetic mapping, providing insights into complex traits and enabling robust QTL identification.
  • The genetic diversity of DO mice enhances the generalizability of findings and avoids idiosyncratic genetic context limitations.
  • The CC inbred strains serve as a resource for validating DO mapping results, with rapidly developing informatics tools supporting these populations.