Experiment
Linkage analysis was performed on 191 male (C57BL/6J x DBA/2J)F2 intercross mice using 885 SNP markers to identify QTL associated with aristolochic acid-induced nephrotoxicity (AAIN). AAIN was measured by proximal tubule dysfunction after exposure to AA, by measures of urinary albumin, glucose, and NAG activity. C57BL/6J and DBA/2J were used as resistant and sensitive strains, respectively.
QTL Aanq1 maps to 56.5 - 70.7 Mb on Chromosome 4 with its peak at rs6254381 (63.3 Mb; LOD score not given) in linkage with AAIN.
After the identification of Aanq1, a second QTL scan taking Aanq1 into account revealed three additional interacting QTL: Aanq2, Aanq3, and Aanq4.
QTL Aanq2 maps to 116.2 - 126.1 Mb on Chromosome 4 with its peak at 121.3 Mb (LOD score not given) in linkage with AAIN.
QTL Aanq3 maps to 113.2 - 121.8 Mb on Chromosome 9 with its peak at 118 Mb (LOD score not given) in linkage with AAIN.
QTL Aanq4 maps to 125 - 134.2 Mb on Chromosome 6 with its peak at 127.9 Mb (LOD score not given) in linkage with AAIN.
A single DBA/2J Aanq1 allele conferred sensitivity to AAIN in a dominant fashion.
Aanq2 confers sensitivity to AAIN in an additive fashion, and Aanq3 confers sensitivity to AAIN in a recessive fashion. Aanq2 and Aanq3 interact - heterozygosity at Aanq2 decreases the effect of a DBA/2J allele at Aanq3.
Aanq4 confers sensitivity to AAIN in adominant fashion. Aanq4 and Aanq1 interact for AA-induced nephropathy. A DBA/2J allele at Aanq4 increases the effect of Aanq1. Aanq4 does not interact significantly with Aanq1 for baseline renal function.