Fine mapping of trypanosomiasis resistance loci in murine advanced intercross lines

We have previously reported the results of genome-wide searches in two muri ne F-2 populations for QTLs that influence survival following Trypanosoma c ongolense infection. Three loci, Tir1, Tir2, and Tir3 were identified and m apped to mouse Chromosomes (Chrs) 17, 5, and 1 respectively, with confidenc e intervals (CIs) in the range 10-40 cM. The size of these CIs is to a larg e degree the consequence of limited numbers of recombination events in smal l chromosomal regions in F-2 populations. A number of population designs ha ve been proposed to increase recombination levels in crosses, one of which is the advanced intercross line (AIL). Here we report fine mapping of Tir1, Tir2, and Tir3 in G6 populations of two independent murine AILs created by crossing the C57BL/6J strain with the A/J and BALB/cJ strains, respectivel y. Data were analyzed by two methods that gave equally informative and simi lar results. The three QTLs were confirmed in the A/J x C57BL/6J AIL and in the combined data set, but Tir2 was apparently lost from the BALB/cJ x C57 BW6J AIL. The reduction in CIs for the Tir loci ranged from 2.5 to more tha n ten-fold in G6 populations by comparison with CIs obtained previously in the equivalent F-2, generations. Mapping in the AILs also resolved the Tir3 locus into three trypanosomiasis resistance QTLs, revealing a degree of co mplexity not evident in extensive studies at the F-2 level.