Showing papers by "Alan J. Teale published in 2000"

Fine mapping of trypanosomiasis resistance loci in murine advanced intercross lines.

Abstract: We have previously reported the results of genome-wide searches in two murine F2 populations for QTLs that influence survival following Trypanosoma congolense infection. Three loci, Tir1, Tir2, and Tir3, were identified and mapped to mouse Chromosomes (Chrs) 17, 5, and 1 respectively, with confidence intervals (CIs) in the range 10–40 cM. The size of these CIs is to a large degree the consequence of limited numbers of recombination events in small chromosomal regions in F2 populations. A number of population designs have 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, respectively. Data were analyzed by two methods that gave equally informative and similar results. The three QTLs were confirmed in the A/J × C57BL/6J AIL and in the combined data set, but Tir2 was apparently lost from the BALB/cJ × C57BL/6J AIL. The reduction in CIs for the Tir loci ranged from 2.5 to more than ten-fold in G6 populations by comparison with CIs obtained previously in the equivalent F2 generations. Mapping in the AILs also resolved the Tir3 locus into three trypanosomiasis resistance QTLs, revealing a degree of complexity not evident in extensive studies at the F2 level.

Strategies to optimize marker-assisted introgression of multiple unlinked QTL.

Abstract: To optimize designs to implement marker-assisted introgression programs aiming to introgress three unlinked quantitative trait loci (QTL), the present paper studies different alternatives versus a traditional backcross or intercross phase. Four alternative backcross strategies appear to be more advantageous by having 50% less genotyping load than a traditional backcross strategy tracking all three QTL at a time through a single line. A multiplication phase following the selection of homozygous animals at the three QTL as an intercross alternative allows doubling of the number of homozygous animals in a mouse model compared with the first intercross generation. Within the same model, a second intercross alternative with individuals carrying all three QTL at the first intercross results in a 12-fold increase in the number of homozygous animals obtained in the first intercross generation. The same ranges of decrease are observed in the number of animals to be genotyped and the number of genotypings when targeting a fixed number of homozygous animals. An option, with two lines each carrying two QTL through the backcross phase and coupled with the second intercross alternative, appears to be the best introgression alternative. This option requires 76% fewer genotypings, 68% fewer animals to be genotyped, and costs 75% less than an option in which all three QTL are introgressed through a single line.

Evidence for genomic imprinting of the major QTL controlling susceptibility to trypanosomiasis in mice.

Abstract: SUMMARY Inbred strains of laboratory mice exhibit marked differences in survival time following infection with Trypanosoma congolense, the principal cause of trypanosomiasis in African livestock. The difference in survival time between the relatively resistant C57BL/6 J and more susceptible BALB/c inbred strains has been attributed to three quantitative trait loci (QTLs), Tir1, Tir2 and Tir3. In order to determine whether there was a parent-of-origin effect on this trait, four backcross populations derived from the C57BL/6 J and BALB/c parental strains were bred and inoculated with T. congolense. The two populations with F1 fathers and BALB/c mothers had a significantly greater overall survival rate than the two populations with BALB/c fathers and F1 mothers. This pattern of inheritance suggested the involvement of imprinted genes. Genotyping with markers at the three QTLs controlling susceptibility revealed that the difference in survival time was consistent with genomic imprinting of the QTL of largest effect, Tir1.