Using the emerging Collaborative Cross to probe the immune system

J. Phillippi, Y. Xie, D. R. Miller, T. A. Bell, Z. Zhang, A. B. Lenarcic, D. L. Aylor, S. H. Krovi, D. W. Threadgill, F. Pardo-Manuel De Villena, W. Wang, W. Valdar, J. A. Frelinger

Research output: Contribution to journalArticle

42 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)38-46
Number of pages9
JournalGenes and Immunity
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2014

Keywords

  • Collaborative Cross
  • FcεR
  • QTL

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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    Phillippi, J., Xie, Y., Miller, D. R., Bell, T. A., Zhang, Z., Lenarcic, A. B., Aylor, D. L., Krovi, S. H., Threadgill, D. W., Pardo-Manuel De Villena, F., Wang, W., Valdar, W., & Frelinger, J. A. (2014). Using the emerging Collaborative Cross to probe the immune system. Genes and Immunity, 15(1), 38-46. https://doi.org/10.1038/gene.2013.59