UNC Systems Genetics
Who are we?
We are a multidisciplinary research group focused on a systems genetics approach to understanding diseases, development, aging, and fertility in the mouse. Our projects range from the development of new community resources, such as the Collaborative Cross, to the development of tools and assays for measuring genetic diversity and discerning genomic structure.
The Collaborative Cross
In 2002, the members of the Complex-Trait Consortium proposed to develop a new mouse genetics resource called the Collaborative Cross (CC). The CC was envisioned as a reference population for mapping multigenic traits that would be free of population structure. The CC would be a new panel of recombinant-inbred lines generated by randomizing the genetic diversity of existing inbred mouse resources. After extensive discussions eight “founders” were chosen representing the three major Mus musculus subspecies (M. m. musculus, M. m. domesticus, and M. m. castaneus): A/J, C57BL/6J, 129S1Sv/ImJ, NOD/ShiLtJ, NZO/H1LtJ, CAST/EiJ, PWK/PhJ, and WSB/EiJ.
The CC project formally began in 2004 at The Jackson Laboratory with the generation of a full diallel cross among the eight founder strains. The resulting F1 population was shipped to three breeding sites at the Oak Ridge National Laboratory (ORNL) in Oak Ridge, Tennessee, USA, the International Livestock Research Institute (ILRI) in Nairobi, Kenya, and the University of Western Australia in Perth, Austrailia. The ORNL population was eventually moved to the University of North Carolina (UNC) in Chapel Hill, North Carolina and the ILRI population moved to Tel Aviv University (TAU) in Tel Aviv, Israel.
As lines near completion they are genotyped and relocated to UNC as necessary where they are finished. Those strains without breeding errors are rederived into a clean facility where they are subjected to marker-assisted inbreeding until completed.
CC lines will be distributed in two stages. A set of 'Distributable' lines that are between 90% and 97% inbred. Genomic maps of the distributable strain's fixed and segregating regions are provided. 'Completed' lines are declared when they are at least 98% homozygous. Animals can be shipped from either UNC's SPF facility (designated health status '2') or the '1' barrier facility.
Distributable CC lines maintain their original strain designations. Lines started at ORNL are designated by the prefix 'OR'. Lines started in Kenya and currently at Tel Aviv University are designated with the prefix 'IL'. Finally, lines started by Geniad in Western Australia are designated with the prefix 'AU'.
The final panel of CC lines will come from the three combined populations and they will be assigned a permanant strain name with prefix 'CC', a sequential strain number, and a laboratory registration code of Unc for lines originated in the United States, Tau for line that originated in Isreal, and Gen for lines originating from Australia.
You can find information on ordering distributable and completed strains here.
October 21, 2012: We have developed, in collaboration with Neogen's Geneseek division, a new low-cost high-density genotyping platform called MegaMUGA. MegaMUGA is built on the Illumina Infinium platform and was designed to expand the number of markers and versatility of the successful Mouse Universal Genotyping Array (MUGA). It extends MUGA from 7.5K to 77.8K markers, and includes all MUGA markers as a subset. There are three types of probes in MegaMUGA. In addition to traditional SNP probes, we have also introduced a second probe type for tracking known structural variants (insertions, deletions and duplications). A third probe type was designed to detect the presence of sequences present only in genetically engineered mice (Cre, Luciferase, etc).
The vast majority of MegaMUGA probes ascertain traditional biallelic SNPs. SNPs were selected to be distributed across the entire genome including the mitochondria and the Y chromosome with an average spacing of 33 Kb. For the autosomes, these probes were distributed as evenly as possible based on new linkage map for the mouse with a slight excess of probes in the telomeric regions to facilitate detection of recombination events in these regions. SNPs were selected to be informative in most mouse populations (including wild mice and multiple Mus species) with a special emphasis for markers that are informative in the Collaborative Cross and Diversity Outbred populations.
Preliminary genotypes from MegaMUGA are available here. We are in the process of QCing MegaMUGA's markers and tuning our calling algorithms to handle its special probes.
We have developed three genotyping platforms for assessing the genetic architecture of various mouse resources, including the developing Collaborative Cross. Using a 550K marker genotyping platform called the Mouse Diversity Array (MDA), we have genotyped nearly every available classical laboratory mouse strain, wild-derived inbred strain, numerous F1 crosses, and wild mice. Genotypes along with various QC and visualization tools for over 350 common mouse strains are provided at this website. Using a highly-informative custom 7.5K marker genotyping platform called the Mouse Universal Genotyping Array (MUGA) we have genotyped 458 extant lines from UNC, TAU, and GND using MUGA and have developed a novel algorithm for inferring the inherited haplotypes using hybridization intensity patterns. MUGA has also been used to monitor and accelerate the inbreeding process of the developing Collaborative Cross strains. In addition, a large collection of common laboratory strains, murine-derived cell lines, and outbred mouse resources have been genotyped using MUGA. These genotypes as well as a collection of comparative genomics analysis tools are available from this website.
Information about mouse genotyping services are available here.
© 2012 UNC Systems Genetics Core Facility