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The First Studies Utilizing The Collaborative Cross Mice Are Published In Genome Research

July 14, 2011

The Collaborative Cross (CC) represents a large collection of new inbred mouse strains created by the mouse genetics community aimed at revolutionizing the study of complex genetic traits and diseases. Derived from classical inbred strains and wild-derived strains, the CC captures nearly 90% of known genetic variation in laboratory mice, far surpassing more commonly used inbred strains. The CC is a tool to integrate studies of gene function and gene networks, allowing the prediction and testing of biological models based on the whole organism, critical to the development of personalized therapies for humans. Genome Research has published three articles online in-advance utilizing strains from the emerging Collaborative Cross mouse strains.

1. Collaborative Cross strains facilitate mapping of causative loci

In this work, Aylor and colleagues performed an experiment called the “the pre-CC study,” the first genetic data and analysis from the emerging strains of the CC. Their investigation revealed that the genomes of CC strains are genetically diverse and contain balanced contributions from each founding strain. Highlighting the statistical power provided by the CC, Aylor et al. utilized ancestry information of the CC strains to map genetic loci for a Mendelian trait (white head-spotting), a complex trait (body weight), and a molecular trait (gene expression in the liver), demonstrating the ancestry-based approach to be superior to established marker-based methods for trait loci discovery.

Reference: Aylor DL et al. Genetic analysis of complex traits in the emerging collaborative cross. Genome Res. doi: 10.1101/gr.111310.110

2. Breeding effects in the Collaborative Cross

The development of the Collaborative Cross presents a unique opportunity to investigate how the breeding of inbred strains affects genetic structure and the diversity of phenotypes. In this paper, Philip et al. have evaluated the range of many traits in late inbreeding populations of the CC, including such phenotypes as body weight, tail length, heart weight, and behavioral traits. Despite the influence of breeding selection in the CC lines, detection of major genetic loci regulating trait variation remained possible. This analysis revealed the scope of phenotypic variation that will be present in the finished strains of the CC.

Reference: Philip VM et al. Genetic analysis in the Collaborative Cross breeding population. Genome Res. doi: 10.1101/gr.113886.110

3. Mapping host susceptibility to fungal infection

Aspergillosis is a serious disease in humans, particularly in immune-compromised individuals, caused by infection with the fungus Aspergillus. The mouse has been an important model for studying Aspergillus infection, but classical laboratory strains of mice used in these studies arose from a small set of founders and lack most of the genetic variation present in wild mice, limiting researchers’ ability to identify additional genetic loci relevant to disease.

In this study, Durrant and colleagues utilized inbred mouse strains from the Collaborative Cross, taking advantage of the genetic contribution of wild-derived strains, to identify novel loci that confer susceptibility to infection with the fungus Aspergillus. By integrating genetic variation data from the genomes of the founding strains of the CC, Durrant et al. further refined the genetic loci associated with Aspergillus susceptibility to suggest specific candidate genes.

Reference: Durrant C et al. Collaborative Cross mice and their power to map host susceptibility to Aspergillus fumigatus infection. Genome Res. doi: 10.1101/gr.118786.110

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