title: Using the emerging Collaborative Cross to probe the immune system.
abstract: The Collaborative Cross (CC) is an emerging panel of recombinant inbred (RI) mouse strains. Each strain is genetically distinct but all descended from the same eight inbred founders. In 66 strains from incipient lines of the CC (pre-CC), as well as the 8 CC founders and some of their F1 offspring, we examined subsets of lymphocytes and antigen-presenting cells. We found significant variation among the founders, with even greater diversity in the pre-CC. Genome-wide association using inferred haplotypes detected highly significant loci controlling B-to-T cell ratio, CD8 T-cell numbers, CD11c and CD23 expression. Comparison of overall strain effects in the CC founders with strain effects at QTL in the pre-CC revealed sharp contrasts in the genetic architecture of two traits with significant loci: variation in CD23 can be explained largely by additive genetics at one locus, whereas variation in B-to-T ratio has a more complex etiology. For CD23, we found a strong QTL whose confidence interval contained the CD23 structural gene Fcer2a. Our data on the pre-CC demonstrate the utility of the CC for studying immunophenotypes and the value of integrating founder, CC and F1 data. The extreme immunophenotypes observed could have pleiotropic effects in other CC experiments.
authors.affiliation: Department of Immunobiology, University of Arizona, Tucson, AZ, USA.
authors.forename: J
authors.initials: J
authors.lastname: Phillippi
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Xie
authors.affiliation: 1] Department of Genetics, University of North Carolina, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Miller
authors.affiliation: 1] Department of Genetics, University of North Carolina, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Bell
authors.affiliation: Department of Computer Science, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Lenarcic
authors.affiliation: 1] Department of Genetics, University of North Carolina, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Aylor
authors.affiliation: Department of Immunobiology, University of Arizona, Tucson, AZ, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Krovi
authors.affiliation: Department of Genetics, North Carolina State University, Raleigh, NC, USA.
authors.forename: D W
authors.initials: DW
authors.lastname: Threadgill
authors.affiliation: 1] Department of Genetics, University of North Carolina, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: F Pardo-Manuel
authors.initials: FP
authors.lastname: de Villena
authors.affiliation: Department of Computer Science, and the Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, USA.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: 1] Department of Genetics, University of North Carolina, Chapel Hill, NC, USA [2] Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: W
authors.identifier: 0000000224190430
authors.initials: W
authors.lastname: Valdar
authors.affiliation: Department of Immunobiology, University of Arizona, Tucson, AZ, USA.
authors.forename: J A
authors.identifier: 0000000225036267
authors.initials: JA
authors.lastname: Frelinger
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D039521:CD11c Antigen / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006239:Haplotypes; D007125:Immunogenetics / Q000379:methods*; D016131:Lymphocyte Subsets / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics / Q000276:immunology*; D040641:Quantitative Trait Loci; D017455:Receptors, IgE / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D039521:CD11c Antigen; D017455:Receptors, IgE