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Identification of epistasis through a partial advanced intercross reveals three arthritis loci within the Cia5 QTL in mice.

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Author

  • Martina Johannesson
  • Jenny C Karlsson
  • P Wernhoff
  • K S Nandakumar
  • Anna-Karin Lindqvist
  • Lina Olsson
  • A D Cook
  • Åsa Andersson
  • Rikard Holmdahl

Summary, in English

Identification of genes controlling complex diseases has proven to be difficult; however, animal models may pave the way to determine how low penetrant genes interact to promote disease development. We have dissected the Cia5/Eae3 susceptibility locus on mouse chromosome 3 previously identified to control disease in experimental models of multiple sclerosis and rheumatoid arthritis. Congenic strains showed significant but small effects on severity of both diseases. To improve the penetrance, we have now used a new strategy that defines the genetic interactions. The QTL interacted with another locus on chromosome 15 and a partial advanced intercross breeding of the two congenic strains for eight generations accumulated enough statistical power to identify interactions with several loci on chromosome 15. Thereby, three separate loci within the original QTL could be identified; Cia5 affected the onset of arthritis by an additive interaction with Cia31 on chromosome 15, whereas the Cia21 and Cia22 affected severity during the chronic phase of the disease through an epistatic interaction with Cia32 on chromosome 15. The definition of genetic interactions was a prerequisite to dissect the Cia5 QTL and we suggest the partial advanced intercross strategy to be helpful also for dissecting other QTL controlling complex phenotypes.

Department/s

  • Immunology

Publishing year

2005

Language

English

Pages

175-185

Publication/Series

Genes and Immunity

Volume

6

Issue

3

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Immunology in the medical area

Keywords

  • partial advanced intercross
  • collagen-induced arthritis
  • quantitative trait locus

Status

Published

Research group

  • Immunology

ISBN/ISSN/Other

  • ISSN: 1476-5470