High resolution mapping of chromosomal regions controlling resistance to gastrointestinal nematode infections in an advanced intercross line of mice
- 169 Downloads
Fine mapping of quantitative trait loci (QTL) associated with resistance to the gastrointestinal parasite Heligmosomoides polygyrus was achieved on F6/F7 offspring (1076 mice) from resistant (SWR) and susceptible (CBA) mouse strains by selective genotyping (top and bottom 20% selected on total worm count in week 6). Fecal egg counts were recorded at weeks 2, 4, and 6, and the average was also analyzed. Blood packed cell volume in weeks 3 and 6 and five immunological traits (mucosal mast cell protease 1, granuloma score, IgG1 against adult worm, IgG1, and IgE to L4 antigen) were also recorded. On Chromosome 1 single-trait analyses identified a QTL with effects on eight traits located at about 24 cM on the F2 mouse genome database (MGD) linkage map, with a 95% confidence interval (CI) of 20-32 cM established from a multitrait analysis. On Chromosome 17 a QTL with effects on nine traits was located at about 18 cM on the MGD map (CI 17.9-18.4 cM). Strong candidate genes for the QTL position on Chromosome 1 include genes known to be involved in regulating immune responses and on Chromosome 17 genes within the MHC, notably the Class II molecules and tumor necrosis factor.
KeywordsQuantitative Trait Locus Quantitative Trait Locus Effect Significant Quantitative Trait Locus Quantitative Trait Locus Location Single Quantitative Trait Locus
The authors acknowledge the technical inputs in the helminthology laboratory of Sam Njomo, Fredrick Moseti, and Sarah Kanyingi; mouse husbandry by Jane Ikanyi, John Kiragu, and Pauline Mbuthia under the supervision of Bob King; and John Wambugu, Moses Ogugo, Daniel Mwangi, and Nemuel Nyamweya for the genotyping in the molecular genetics laboratory. The authors are particularly grateful to Clare Kemp for preparing the color versions of Figs. 2 and 3. This research was funded by a grant from the Wellcome Trust (063810) and by member donors of the CGIAR, and by program-restricted grants to ILRI from the EU and Department for International Development (DfID), UK. Helpful advice was generously provided by Prof. A.B. Korol and Prof. Jan Bradley.
- Gasbarre LC, Miller JE (2000) Genetics of helminth resistance. In: Breeding for Disease Resistance in Farm Animals, 2nd ed., Axford REF, Bishop SC, Nicholas FW, Owen JB (eds.) (Wallingford, Oxfordshire, UK: CAB International) pp 129–152Google Scholar
- Gray GD, Woolaston RR, Eaton BT (1995) Breeding for resistance to infectious diseases of small ruminants [Canberra, Australia: Australian Centre for International Agricultural Research (ACIAR)), Monogr No. 34Google Scholar
- Lincoln S, Daly M, Lander ES (1994) MAPMAKER/QTL 1.1 Whitehead Institute Technical Report Vol. 2 (Cambridge, MA: Whitehead Institute)Google Scholar
- Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual, 2nd ed. (Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press)Google Scholar
- Wakelin D. (2000) Rodent models of genetic resistance to parasitic infections In: Breeding for Disease Resistance in Farm Animals, 2nd ed., Axford REF, Bishop SC, Nicholas FW, Owen JB (eds.) (Wallingford, Oxfordshire, UK: CAB International) pp 107–126Google Scholar
- Wang M, Lemon W J, Liu G, Wang Y, Iraqi F, et al. (2003a) Fine mapping and identification of candidate pulmonary adenoma susceptibility 1 genes using advanced intercross lines. Cancer Res 63:3317–3324Google Scholar