Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Localization of genes controlling resistance to trypanosomiasis in mice

Abstract

Tsetse fly-transmitted trypanosomes (Trypanosoma spp.) cause ‘sleeping sickness’ in man and have a serious impact on livestock-based agriculture in large areas of Africa1. Multigene control of variation in susceptibility to trypanosomiasis is known to occur in mice, where the C57BI/6 (B6) strain is relatively resistant and the A/J (A) and Balb/c (B) strains are susceptible2,3. Such resistance is also well described among several types of west African cattle4. We report here the results of genome-wide scans for genes controlling this trait in the B6 mouse using crosses with two different susceptible strains. Regions on mouse chromosomes 5 and 17 were found to be important in determining resistance in both crosses while an additional region on chromosome 1 showed evidence of involvement in only one cross. We confirmed the size of the effect due to chromosome 17 in F3 intercross populations fixed for alternative parental chromosomes. The three loci are of large effect and account for most of the genetic variation in both F2 populations. We propose that they be designated Tir1, Tir2 and Tir3.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Winrock International. Assessment of Animal Agriculture in Sub-Saharan Africa(Winrock International Institute for Agricultural Development, Arkansas, 1992).

  2. 2

    Morrison, W.I., Roelants, G.E., Mayor-Withey, K.S. & Murray, M. Susceptibility of inbred strains of mice to Trypanosoma congolense: correlation with changes in spleen lymphocyte populations. Clin. Exp. Immunol. 32, 25–40 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 3

    Morrison, W.I. & Murray, M. Trypanosoma congolense: Inheritance of susceptibility to infection in inbred strains of mice. Exp. Parasitol. 48, 364–374 (1979).

    CAS  Article  Google Scholar 

  4. 4

    Murray, M. & Trail, J.C.M. Genetic resistance to animal trypanosomiasis in Africa. Prev. Vet Med. 2, 541–551 (1984).

    Article  Google Scholar 

  5. 5

    Dietrich, W.F. et al. A comprehensive genetic map of the mouse genome. Nature. 380, 149–152 (1996).

    CAS  Article  Google Scholar 

  6. 6

    Paterson, E. et al. Resolution of quantitative traits into mendelian factors using a complete RFLP linkage map. Nature 335, 721–726 (1994).

    Article  Google Scholar 

  7. 7

    Lincoln, S., Daly, M. & Lander, E.S. Mapping genes controlling quantitative traits with MAPMAKER/QTL 1.1. in Whitehead Institute Technical Report Vol. 2, (Whitehead Institute, Cambridge, Massachusetts, 1994).

    Google Scholar 

  8. 8

    Whithead Institute & MIT Center for Genome Research. Genomic Map of the Mouse, Database Release 10, June 1996).

  9. 9

    Lander, E. & Kruglyak, L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genet. 11, 241–247 (1995).

    CAS  Article  Google Scholar 

  10. 10

    Albright, J.W. & Albright, J.F. Differences in resistance to Trypanosoma musculi infection among strains of inbred mice. Infect. Immun. 33, 364–371 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11

    Degee, A.L.W., Levine, R.F. & Mansfield, J.M. Genetics of resistance to the african trypanosomes. IV. Heredity of resistance and variable surface glycoprotein-specific immune-responses. J. Immunol. 140, 283–288 (1988).

    CAS  Google Scholar 

  12. 12

    Bakhiet, M. et al. Control of parasitemia and survival during trypanosoma-brucei-brucei infection is related to strain-dependent ability to produce i1–4. J. Immunol. 157, 3518–3526 (1996).

    CAS  PubMed  Google Scholar 

  13. 13

    Levine, R.F. & Mansfield, J.M. Genetics of resistance to African trypanosomes: Role of the H-2 locus in determining resistance to infection with Trypanosoma rhodesiense. Infect. Immun. 34, 513–518 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14

    Wallace, G.D., Buller, R.M.L & Morse, H.C Genetic determinants of resistance to ectromelia (mousepox) virus-induced mortality. J Virol. 55, 890–891 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. 15

    Brownstein, D.G. & Gras, L. Chromosome mapping of Rmp-4, a gonad-dependent gene encoding host resistance to mousepox. J. Virol. 69, 6958–6964 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16

    Rifkin, M.R. Identification of the trypanocidal factor in normal human serum: High density lipoprotein. Proc. Natl. Acad. Sci. USA 75, 3450–3454 (1978).

    CAS  Article  Google Scholar 

  17. 17

    Eshed, Y. & Zamir, D. Less-than-additive epistatic interactions of quantitative trait loci in tomato. Genetics 143, 1807–1817 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18

    Doebley, J., Stec, A. & Gustus, C. Teosinte branched 1 and the origin of maize: evidence for epistasis and the evolution of dominance. Genetics 141, 333–346 (1996).

    Google Scholar 

  19. 19

    Lark, K.G., Chase, K., Adler, F., Mansur, L.M. & Orf, J.H. Interactions between quantitative trait loci in soybean in which trait variation at one locus is conditional upon a specific allele at another. Proc. Natl. Acad. Sci. USA 92, 4656–4660 (1995).

    CAS  Article  Google Scholar 

  20. 20

    Darvasi, A. Interval specific congenic strains (ISCS): An experimental design for mapping a QTL into a one centimorgan interval. Mamm. Genome 8, 163–167 (1997).

    CAS  Article  Google Scholar 

  21. 21

    Darvasi, A. & Seller, M. Advanced intercross lines, an experimental population for fine genetic mapping. Genetics 141, 1199–207 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22

    Nantulya, V.M., Musoke, A.J., Rurangirwa, F.R. & Moloo, S.K. Resistance of cattle to tsetse-transmitted challenge with Trypanosoma brucei or Trypanosoma congolense after spontaneous recovery from syringe passed infections. Infect. Immun. 43, 735–738 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23

    Sambrook, J., Fritsch, F.E. & Maniatis, T. Molecular Cloning; A Laboratory Manual (Cold Spring Harbor Press, New York, 1989).

    Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Kemp, S., Iraqi, F., Darvasi, A. et al. Localization of genes controlling resistance to trypanosomiasis in mice. Nat Genet 16, 194–196 (1997). https://doi.org/10.1038/ng0697-194

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing