Journal article
Genetic analysis in the Collaborative Cross breeding population
Genome research, Vol.21(8), pp.1223-1238
08/01/2011
DOI: 10.1101/gr.113886.110
PMCID: PMC3149490
PMID: 21734011
Abstract
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.
Details
- Title: Subtitle
- Genetic analysis in the Collaborative Cross breeding population
- Creators
- Vivek M Philip - Oak Ridge National LaboratoryGreta Sokoloff - Univ Chicago, Dept Human Genet, Chicago, IL 60637 USACheryl L Ackert-Bicknell - Jackson Lab, Bar Harbor, ME 04609 USAMartin Striz - Univ Kentucky, Dept Biol, Lexington, KY 40506 USALisa Branstetter - Oak Ridge Natl Lab, Syst Genet Grp, Biosci Div, Oak Ridge, TN 37831 USAMelissa A Beckmann - Oak Ridge Natl Lab, Syst Genet Grp, Biosci Div, Oak Ridge, TN 37831 USAJason S Spence - Oak Ridge Natl Lab, Syst Genet Grp, Biosci Div, Oak Ridge, TN 37831 USABarbara L Jackson - Oak Ridge Natl Lab, Stat & Data Sci Grp, Div Math & Comp Sci, Oak Ridge, TN 37831 USALeslie D Galloway - Univ Tennessee, Dept Ecol & Evolutionary Biol, Knoxville, TN 37996 USAPaul Barker - Oak Ridge Natl Lab, Syst Genet Grp, Biosci Div, Oak Ridge, TN 37831 USAAnn M Wymore - Oak Ridge Natl Lab, Syst Genet Grp, Biosci Div, Oak Ridge, TN 37831 USAPatricia R Hunsicker - Oak Ridge Natl Lab, Syst Genet Grp, Biosci Div, Oak Ridge, TN 37831 USADavid C Durtschi - Oak Ridge Natl Lab, Syst Genet Grp, Biosci Div, Oak Ridge, TN 37831 USAGinger S Shaw - Oak Ridge Natl Lab, Syst Genet Grp, Biosci Div, Oak Ridge, TN 37831 USASarah Shinpock - Oak Ridge Natl Lab, Syst Genet Grp, Biosci Div, Oak Ridge, TN 37831 USAKenneth F Manly - Univ Tennessee, Hlth Sci Ctr, Ctr Genom & Bioinformat, Memphis, TN 38163 USADarla R Miller - Oak Ridge Natl Lab, Syst Genet Grp, Biosci Div, Oak Ridge, TN 37831 USAKevin D Donohue - Univ Kentucky, Dept Elect & Comp Engn, Lexington, KY 40506 USACymbeline T Culiat - Oak Ridge Natl Lab, Syst Genet Grp, Biosci Div, Oak Ridge, TN 37831 USAGary A Churchill - Jackson Lab, Bar Harbor, ME 04609 USAWilliam R Lariviere - Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15260 USAAbraham A Palmer - Univ Chicago, Dept Human Genet, Chicago, IL 60637 USABruce F O'Hara - Univ Kentucky, Dept Biol, Lexington, KY 40506 USABrynn H Voy - Oak Ridge Natl Lab, Syst Genet Grp, Biosci Div, Oak Ridge, TN 37831 USAElissa J Chesler - Oak Ridge Natl Lab, Syst Genet Grp, Biosci Div, Oak Ridge, TN 37831 USA
- Resource Type
- Journal article
- Publication Details
- Genome research, Vol.21(8), pp.1223-1238
- Publisher
- COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
- DOI
- 10.1101/gr.113886.110
- PMID
- 21734011
- PMCID
- PMC3149490
- ISSN
- 1088-9051
- eISSN
- 1549-5469
- Number of pages
- 16
- Grant note
- Ellison Medical Foundation ORNL Office of Biological and Experimental Research, Office of Science, US Department of Energy
- Language
- English
- Date published
- 08/01/2011
- Academic Unit
- Psychological and Brain Sciences
- Record Identifier
- 9984256840902771
Metrics
15 Record Views