TY - JOUR
T1 - Fine mapping of collagen-induced arthritis quantitative trait loci in an advanced intercross line
AU - Yu, Xinhua
AU - Bauer, Kristin
AU - Wernhoff, Patrik
AU - Koczan, Dirk
AU - Möller, Steffen
AU - Thiesen, Hans Jürgen
AU - Ibrahim, Saleh M.
PY - 2006/11/15
Y1 - 2006/11/15
N2 - The generation of advanced intercross lines (AIL) is a powerful approach for high-resolution fine mapping of quantitative trait loci (QTLs), because they accumulate much more recombination events compared with conventional F 2 intercross and N2 backcross. However, the application of this approach is severely hampered by the requirements of excessive resources to maintain such crosses, i.e., in terms of animal care, space, and time. Therefore, in this study, we produced an AIL to fine map collagen-induced arthritis (CIA) QTLs using comparatively limited resources. We used only 308 (DBA/1 × FVB/N)F11/12 AIL mice to refine QTLs controlling the severity and onset of arthritis as well as the Ab response and T cell subset in CIA, namely Cia2, Cia27, and Trmq3. These QTLs were originaly identified in (DBA/1 × FVB/N)F2 progeny. The confidence intervals of the three QTLs were refined from 40, 43, and 48 Mb to 12, 4.1, and 12 Mb, respectively. The data were complemented by the use of another QTL fine-mapping approach, haplotype analysis, to further refine Cia2 into a 2-Mb genomic region. To aid in the search for candidate genes for the QTLs, genome-wide expression profiling was performed to identify strain-specific differentially expressed genes within the confidence intervals. Of the 1396 strain-specific diferentially expressed genes, 3, 3, and 12 genes were within the support intervals of the Cia2, Cia27, and Trmq3, respectively. In addition, this study revealed that Cia27 and Trmq3 controlling anti-C11 IgG2a Ab and CD4:CD8 T cell ratio, respectively, also regulated CIA clinical phenotypes.
AB - The generation of advanced intercross lines (AIL) is a powerful approach for high-resolution fine mapping of quantitative trait loci (QTLs), because they accumulate much more recombination events compared with conventional F 2 intercross and N2 backcross. However, the application of this approach is severely hampered by the requirements of excessive resources to maintain such crosses, i.e., in terms of animal care, space, and time. Therefore, in this study, we produced an AIL to fine map collagen-induced arthritis (CIA) QTLs using comparatively limited resources. We used only 308 (DBA/1 × FVB/N)F11/12 AIL mice to refine QTLs controlling the severity and onset of arthritis as well as the Ab response and T cell subset in CIA, namely Cia2, Cia27, and Trmq3. These QTLs were originaly identified in (DBA/1 × FVB/N)F2 progeny. The confidence intervals of the three QTLs were refined from 40, 43, and 48 Mb to 12, 4.1, and 12 Mb, respectively. The data were complemented by the use of another QTL fine-mapping approach, haplotype analysis, to further refine Cia2 into a 2-Mb genomic region. To aid in the search for candidate genes for the QTLs, genome-wide expression profiling was performed to identify strain-specific differentially expressed genes within the confidence intervals. Of the 1396 strain-specific diferentially expressed genes, 3, 3, and 12 genes were within the support intervals of the Cia2, Cia27, and Trmq3, respectively. In addition, this study revealed that Cia27 and Trmq3 controlling anti-C11 IgG2a Ab and CD4:CD8 T cell ratio, respectively, also regulated CIA clinical phenotypes.
UR - http://www.scopus.com/inward/record.url?scp=33750839242&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.177.10.7042
DO - 10.4049/jimmunol.177.10.7042
M3 - Article
C2 - 17082620
AN - SCOPUS:33750839242
SN - 0022-1767
VL - 177
SP - 7042
EP - 7049
JO - Journal of Immunology
JF - Journal of Immunology
IS - 10
ER -