Genomic Resources for the Collaborative Cross In response to NIH FOA PAR-17-273 PI: Leonard McMillan We propose to develop unique and unprecedented genomic resources for the experimental genetics community in support of the Collaborative Cross (CC). The CC is an emergent genetics resource consisting of more than seventy new isogenic mouse strains with genomes derived from eight founders that captures most of diversity in Mus musculus. As reported in June?s issue of Genetics, we have recently done full-genome sequencing for samples from each CC strain.
The Aims of this proposal will be: 1. To assemble and annotate unique individual genomes for each reproducible CC strain. 2. To provide tools that aid in experimental designs using the CC. In particular, how to design recombinant inbred intercrosses, that provide a sufficiently sized set of balanced and reproducible outbred samples. We will also provide tools that fix particular genes for testing against variable genetic backgrounds. 3. We propose to develop custom -omics analysis pipelines that leverage the unprecedented genomics annotation available for the CC to support the exploration allele specific effects. Our primary goal is to bootstrap the use of the CC within the medical research community, with the hopes that after the five years of support these resources will be self-sustaining through selling mice by the UNC System?s Genetics Core facility. This proposal has two Principal Investigators (PIs). The contact PI is Professor Leonard McMillan from UNC?s department of Computer Science. He is joined by PI Fernando Pardo-Manuel de Villena, PhD. Dr. McMillan has been the primary bioinformatics expert and tool developer for the CC over the past 8+ years of its development. Dr. Pardo-Manuel de Villena is a geneticist who led the development of the Collaborative Cross. Together we bring extensive expertise in computational biology, genetics, and genomics to ensure that the CC is the premier mammalian genetic reference population and a source of new mouse models of human disease.
For decades the laboratory mouse has been the standard mammalian model organism in biomedical research. More recently, several large new resources have been developed to address perceived limitations and to enhance the value of the mouse as a model of human diseases. The Collaborative Cross (CC) is one such resource that specifically aims to be the foundation for systems genetics approaches to modeling common human disease. The CC consists of more than seventy new inbred mouse strains with genomes derived from eight founders that captures most of diversity in the laboratory mouse. In this application, we will develop genetic and genomic resources and tools to take full advantage of the CC, facilitate its use by non-geneticists and increase the rigor and reproducibility of ongoing studies.