Publication Details

Genetics of colitis susceptibility in IL-10-deficient mice: backcross versus F2 results contrasted by principal component analysis.

Authors:Mhler M, Most C, Schmidtke S, Sundberg JP, Li R, Hedrich HJ, Churchill GA
Title:Genetics of colitis susceptibility in IL-10-deficient mice: backcross versus F2 results contrasted by principal component analysis.
Journal:Genomics Sep 2002 , Vol 80 , pp. 274-82
Abstract:Interleukin-10-deficient (Il10(-/-)) mice on a C3H/HeJBir genetic background develop more severe colitis than those on a C57BL/6J background. We performed genome screens for quantitative trait loci (QTLs) regulating colitis susceptibility in this model system using two first backcross populations derived from these two strains. To reduce the complexity of this analysis, the information from numerous histologic phenotypes was summarized by principal component analysis. A similar approach was applied to previously published data from an F2 intercross (involving the same progenitor strains), which allowed us to ascertain all six previously reported cytokine-deficiency-induced colitis susceptibility loci (Cdcs1-6) with main and/or interacting effects on chromosomes 3, 1, 2, 8, 17, and 18. The colitogenic effect of Cdcs1 was confirmed in the backcross to C3H/HeJBir-Il10(-/-). Its effect was epistatically modified by another locus on chromosome 12. In addition, three main effect QTLs on chromosomes 4, 5, and 12 were identified in the backcross to C57BL/6J-Il10(-/-). Analyses of the modes of inheritance in these crosses revealed colitogenic contributions by both parental genomes. These findings show the complexity of inheritance underlying susceptibility to colitis and illustrate why detection of human inflammatory bowel disease loci has proven to be so difficult.   PUBMED: 12213197
Ontological Annotations:
  • D040641: Quantitative Trait Loci (Publication, NCBO Annotator)
  • MP:0002816: colitis (Publication, NCBO Annotator)
  • D006801: Humans (Publication, NCBO Annotator)
  • D002875: Chromosomes (Publication, NCBO Annotator)
  • D051379: Mice (Publication, NCBO Annotator)
  • MA:0001524: bowel (Publication, NCBO Annotator)
  • D014918: Wills (Publication, NCBO Annotator)
  • D003092: Colitis (Publication, NCBO Annotator)
  • GO:0005694: chromosome (Publication, NCBO Annotator)
  • D015212: Inflammatory Bowel Diseases (Publication, NCBO Annotator)
  • D025341: Principal Component Analysis (Publication, NCBO Annotator)
  • D005823: Genetics (Publication, NCBO Annotator)
  • D002881: Chromosomes, Human, Pair 12 (Publication, NCBO Annotator)

2 GeneSets from this Publication:

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Expand Tier II Mouse 401 Genes GS135565: cytokine deficiency colitis susceptibility 7 (Cdcs7, Published QTL Chr 12)
Expand Tier II Mouse 401 Genes GS135566: cytokine deficiency colitis susceptibility 8 (Cdcs8, Published QTL Chr 12)