Genetic analysis in the Collaborative Cross breeding population

Journal Article · Sat Jan 01 04:00:00 EST 2011 · Genome Research

DOI:https://doi.org/10.1101/gr.113886.110· OSTI ID:1034663

Philip, Vivek ^[1]; Sokoloff, Greta ^[2]; Ackert-Bicknell, Cheryl ^[3]; Striz, Martin ^[4]; Branstetter, Lisa R ^[2]; Beckmann, Melissa ^[2]; Spence, Jason S ^[2]; Jackson, Barbara L ^[2]; Galloway, Leslie D ^[2]; Barker, Gene ^[2]; Wymore, Ann M ^[5]; Hunsicker, Patricia R ^[2]; Durtschi, David W ^[4]; Shaw, Ginger S ^[4]; Shinpock, Sarah G ^[2]; Manly, Kenneth F ^[4]; Miller, Darla R ^[2]; Donahue, Kevin ^[6]; Culiat, Cymbeline T ^[2]; Churchill, Gary A ^[3] ; Lariviere, William R ^[7]; Palmer, Abraham ^[8]; O'Hara, Bruce ^[9]; Voy, Brynn H ^[2]; Chesler, Elissa J ^[2]

---

1. University of Tennessee, Knoxville (UTK)
2. ORNL
3. Jackson Laboratory, The, Bar Harbor, ME
4. University of Kentucky, Lexington
5. Oak Ridge National Laboratory (ORNL)
6. University at Buffalo, NY
7. University of Pittsburgh
8. University of Chicago
9. University of Kentucky

Genetic reference populations in model organisms are critical resources for systems genetic analysis of disease related phenotypes. The breeding history of these inbred panels may influence detectable allelic and phenotypic diversity. The existing panel of common inbred strains reflects historical selection biases, and existing recombinant inbred panels have low allelic diversity. All such populations may be subject to consequences of inbreeding depression. The Collaborative Cross (CC) is a mouse reference population with high allelic diversity that is being constructed using a randomized breeding design that systematically outcrosses eight founder strains, followed by inbreeding to obtain new recombinant inbred strains. Five of the eight founders are common laboratory strains, and three are wild-derived. Since its inception, the partially inbred CC has been characterized for physiological, morphological, and behavioral traits. The construction of this population provided a unique opportunity to observe phenotypic variation as new allelic combinations arose through intercrossing and inbreeding to create new stable genetic combinations. Processes including inbreeding depression and its impact on allelic and phenotypic diversity were assessed. Phenotypic variation in the CC breeding population exceeds that of existing mouse genetic reference populations due to both high founder genetic diversity and novel epistatic combinations. However, some focal evidence of allele purging was detected including a suggestive QTL for litter size in a location of changing allele frequency. Despite these inescapable pressures, high diversity and precision for genetic mapping remain. These results demonstrate the potential of the CC population once completed and highlight implications for development of related populations. Supplementary material consists of Supplementary Table 1 Phenotypic means, variances, ranges and heritabilities for all traits and generations, Supplementary Table 2, all phenotypic values, Supplementary Table 3, multiple QTL mapping.

• Research Organization: Oak Ridge National Laboratory (ORNL); Mouse Genetics Research Facility
• Sponsoring Organization: SC USDOE - Office of Science (SC)
• DOE Contract Number: AC05-00OR22725
• OSTI ID: 1034663
• Journal Information: Genome Research, Journal Name: Genome Research Journal Issue: 8 Vol. 21; ISSN 1088-9051
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
ACCURACY
BREEDING
CONSTRUCTION
DESIGN
DISEASES
GENETIC MAPPING
GENETICS
LITTER SIZE
STRAINS
genetic reference populations
systems genetics