Abstract:
Quantitative trait loci (QTL) mapping and fine mapping in mouse models demonstrates the possibility of localizing genes that determine genetic variations in inbred strains. Previously, three quantitative trait loci (QTL), Tir l, Tir2 and Tir3 on chromosome 17, 5 and 1 respectively associated with resistance to trypanosomosis, were mapped in two F2 resource populations, (C5781./6.1 x A/J) and (C57BL/6] x BALB/cl). The QTL were mapped within l0-40cM genomic intervals (CI). Subsequently, using F6 advanced intercross lines (AILs), the QTL were fine mapped to 8 Smflllel‘ C°"fid="°° interval (Cl), but not sufficient for positional cloning. C31-l/He] and l.29{-l mouse strains are relatively susceptible, however, it is not known if this is due to ‘susceptible’ alleles at the previously identified QTL To determine this, an F2 cross (C57BL/6J X C3H/HeJ) was developed and challenged with Tryponosoma congolense and the response and survival time monitored. interval mapping identified significant QTL on chromosomes 17 and l, however, Tir2 was not confirmed. Following the confirmation of the QTb on chromosome l and l7, the conserved susceptible/resistance (QTLs) regions between A/J, BALB/c.I, C3H/He], 129/J and C57BL/6] were explored using single nucleotide polymorphism (SNP) haplotypes for fine mapping these QTL. The QTL precision was increased significantly from 30-40cM to less than lcM which is now adequate for positional cloning.
