Genetic Variation and Population Substructure in Outbred CD-1 Mice: Implications for Genome-Wide Association Studies

Kimberly A Aldinger,Greta Sokoloff,Abraham A Palmer,Kathleen J Millen,David M Rosenberg,Wim E Crusio

doi:10.1371/journal.pone.0004729

Abstract

Outbred laboratory mouse populations are widely used in biomedical research. Since little is known about the degree of genetic variation present in these populations, they are not widely used for genetic studies. Commercially available outbred CD-1 mice are drawn from an extremely large breeding population that has accumulated many recombination events, which is desirable for genome-wide association studies. We therefore examined the degree of genome-wide variation within CD-1 mice to investigate their suitability for genetic studies. The CD-1 mouse genome displays patterns of linkage disequilibrium and heterogeneity similar to wild-caught mice. Population substructure and phenotypic differences were observed among CD-1 mice obtained from different breeding facilities. Differences in genetic variation among CD-1 mice from distinct facilities were similar to genetic differences detected between closely related human populations, consistent with a founder effect. This first large-scale genetic analysis of the outbred CD-1 mouse strain provides important considerations for the design and analysis of genetic studies in CD-1 mice.

Highlights

CD-1 mice are an inexpensive, robust and readily available outbred population commonly used in toxicology and cancer research [1,2,3]
We evaluated the genetic relationship between CD-1 mice and other Swiss-derived inbred strains, including FVB/NJ, NMRI/br and SWR/J, since these mice are all derived from recent common ancestors
We considered the evidence for detecting unknown familial relationships, or cryptic relatedness, among individual CD-1 mice by assessing departures from HardyWeinberg equilibrium (HWE)

Summary

Introduction

CD-1 mice are an inexpensive, robust and readily available outbred population commonly used in toxicology and cancer research [1,2,3]. They have been widely used for mouse transgenesis experiments, principally due to efficient breeding and large litter sizes. While many large-scale examinations of the genetic architecture of inbred mice have been completed [6,7,8,9,10,11], no comparable evaluations of commercially available outbred strains, including CD-1 mice, have been reported This lack of genome-wide evaluation has created a significant obstacle to realizing the utility of CD-1 mice for genetic research

Methods

Results

Conclusion