Fragmentation of two quantitative trait loci controlling collagen-induced arthritis reveals a new set of interacting subloci
Author
Summary, in English
Linkage analysis of F-2 crosses has led to identification of large numbers of quantitative trait loci (QTL) for complex diseases, but identification of the underlying genes has been more difficult. Reasons for this could be complications that arise from separation of interacting or neighboring loci. We made a partial advanced intercross (PAI) to characterize and fine-map linkage to collagen-induced arthritis in two chromosomal regions derived from the DBA/1 strain and crossed into the B10.Q strain: Cia7 on chromosome 7 and a locus on chromosome 15. Only Cia7 was detected by a previous F-2 cross. Linkage analysis of the PAI revealed a different linkage pattern than the F-2 cross, adding multiple loci and strong linkage to the previously unlinked chromosome 15 region. Subcongenic strains derived from animals in the PAI confirmed the loci and revealed additional subloci. In total, no less than seven new loci were identified. Several loci interacted and three loci were protective, thus partly balancing the effect of the disease-promoting loci. Our results indicate that F-2 crosses do not reveal the full complexity of identified QTLs, and that detection is more dependent on the genetic context of a QTL than the potential effect of the underlying gene.
Department/s
- Immunology
Publishing year
2007
Language
English
Pages
3084-3090
Publication/Series
Journal of Immunology
Volume
178
Issue
5
Links
Document type
Journal article
Publisher
American Association of Immunologists
Topic
- Immunology in the medical area
Status
Published
Research group
- Immunology
ISBN/ISSN/Other
- ISSN: 1550-6606