Marker-assisted introgression of Trypanotolerance QTL in mice

Abstract

A marker-assisted introgression (MAI) experiment was conducted to use genetic markers to transfer each of the three trypanotolerance QTL from a donor mouse strain, C57BL/6, into a recipient mouse strain, A/J. We used a backcross strategy that consisted of selecting two lines, each carrying two of the donor QTL alleles through the backcross (BC) phase. At the fourth BC generation, single-carrier animals were selected for the production of homozygous animal in the intercross phase. The QTL regions (QTLR) were located on chromosomes MMU1, MMU5, and MMU17. Groups of mice with different genotypes and the parental lines were subjected to a challenge with Trypanosoma congolense. The results show that trypanotolerance QTL was successfully moved into the recipient background genotype, yielding a longer survival time. The mean estimated survival time was 57.9, 49.5, and 46.8 days for groups of mice carrying the donor QTL on MMU1, MMU5, and MMU17 on A/J background. The mean estimated survival time was 29.7 days for the susceptible A/J line and 68.8 days for the resistant C57BL/6 line. The estimated QTLR effects are close to 30% smaller than those in the original mapping population which was likely caused by the difference in the background on which the effects of QTLR are tested. This is the first report of successful marker-assisted introgression of QTL in animals. It is experimental proof of the use of genetic markers for marker-assisted introgression in animal breeding.

Biphasic survival analysis of trypanotolerance QTL in mice

“…The data set used in this analysis originates from the MAI experiment reported by Koudandé et al (2005). This experiment was undertaken to introgress three identified chromosomal regions on mouse chromosome 1 (MMU1), 5 (MMU5) and 17 (MMU17) from the donor C57BL/6 line to the recipient A/J line.…”

“…In the last generation, each of the synthetic lines was backcrossed to both parental lines giving a total of 10 groups of mice plus the two parental lines as external controls (Table 1). More details on the MAI scheme are given by Koudandé et al (2005).…”

“…More details on the challenge experiment and their results are described in Koudandé et al (2005). Tables 2 and 3 from Koudandé et al (2005), where group 0 and group 11 correspond here respectively to group A/J and group C57BL/6 in this paper, all other groups are identical.…”

“…Since 1978, most of the resistance studies on trypanosome infection in mice have been using survival measurements as monitors (Kemp et al, 1996(Kemp et al, , 1997Clapcott et al, 2000;Iraqi et al, 2000). Koudandé et al (2005) reported the successful markerassisted introgression (MAI) of trypanotolerance quantitative trait loci (QTL) alleles from the mouse strain C57BL/6 (donor) into the mouse strain A/J (recipient). They found two phases of mortality when analyzing 'time to death' following trypanosome infection of mice.…”

“…In the current paper, we present survival analysis methods that take into account the biphasic mortality pattern and results of reanalyzing the data set generated by Koudandé et al (2005). The methods should prove applicable to the investigation of multiphasic processes in biological systems generally.…”