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High-resolution genetic mapping using the Mouse Diversity outbred population.

Karen L Svenson¹, Daniel M Gatti, William Valdar

¹The Jackson Laboratory, Bar Harbor, Maine 04609, USA. karen.svenson@jax.org

|February 21, 2012

Summary

The JAX Diversity Outbred mouse population offers a unique resource for genetic mapping. This population enables high-resolution mapping of complex traits, identifying specific genes like Foxo1 for serum cholesterol.

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Area of Science:

Genetics
Genomics
Animal Models

Background:

The JAX Diversity Outbred (JDO) mouse population is a novel resource derived from the Collaborative Cross.
It features high heterozygosity and unique allele combinations in each animal, creating significant phenotypic diversity.
This distinct population architecture differs from founder strains, offering new research possibilities.

Purpose of the Study:

To introduce the JAX Diversity Outbred mouse population as a powerful resource for genetic research.
To describe analytical methods for genetic mapping within this population.
To demonstrate the high mapping resolution achievable with the JDO population.

Main Methods:

Utilized randomized outcrossing to maintain the JAX Diversity Outbred population.

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Developed and applied analytical methods for genetic mapping in this outbred resource.

Performed genetic mapping of a serum cholesterol trait to pinpoint candidate genes.

Main Results:

Successfully mapped a serum cholesterol trait to a 2-Mb region on chromosome 3, containing only 11 genes.
Demonstrated the high mapping resolution and power of the JAX Diversity Outbred population.
Reduced candidate polymorphisms to seven SNPs, with five located upstream of the Foxo1 gene.

Conclusions:

The JAX Diversity Outbred population is a valuable resource for genetic mapping and complex trait analysis.
The population architecture facilitates high-resolution mapping, enabling precise identification of genetic loci.
This resource aids in discovering candidate genes, such as Foxo1, involved in specific phenotypic variations.