Abstract
AnN-ethyl-N-nitrosourea (ENU)-induced mutation in theHbb-b1 gene of the mouse hemoglobin-beta complex (Hbb) has been shown to result in a high-oxygen affinity hemoglobin, homologous with hemoglobin Rainier in man (Peters, J.,et al., Genetics 110:709, 1985). Substitution of β145 tyrosine by cysteine had occurred in both human and mouse forms, probably as the result of a point mutation. Provided that sufficient sequence information is available, point mutations can be directly and rapidly analyzed by allele-specific amplification (ASA), as this technique is sensitive enough to detect single nucleotide differences. We report the use of ASA to detect and characterize the mutation in the murine β-globin gene,Hbb-b1 d-m1, and find that the codon for β145 tyrosine (TAC) has been replaced by the codon for cysteine (TGC). Therefore, ENU induced an A:T → G:C transition.
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References
Ballabio, A., Gibbs, R. A., and Caskey, C. T. (1990). PCR test for cystic fibrosis deletion.Nature 343220.
Chehab, F. F., and Kan, Y. W. (1990). Detection of the sickle cell anaemia mutation by colour DNA amplification.Lancet 33415.
Eckert, K. A., Ingle, C. A., Klinedist, T., and Drinkwater, N. R. (1988). Molecular analysis of mutations induced in human cells by N-ethyl-N-nitrosourea.Mol. Carcinogen. 150.
Erhart, M. A., Simons, K. S., and Weaver, S. (1985). Evolution of the mouse β-globin genes: A recent conversion in theHbb s haplotype.Mol. Biol. Evol. 2304.
Fischel-Ghardsian, N., Hirsh, P. C., and Bohlman, M. C. (1990). Rapid detection of the haemoglobin C mutation by allele specific polymerase chain reaction.Am. J. Hum. Genet. 471023.
Fossett, N. G., Arbour-Reily, P., Kilroy, G., McDaniel, M., Mahmoud, J., Tucker, A. B., Chang, S. H., and Lee, W. R. (1990). Analysis of ENU-induced mutations at theAdh locus inDrosophila melanogaster.Mutat. Res. 23173.
Gilmam, J. G. (1976). Mouse haemoglobin beta chains. Comparative sequence data on adult major and minor beta chains from two species,Mus musculus andMus cervicolor.Biochem. J. 159294.
Jones, J., and Peters, J. (1991). An ENU induced mutation in the β-globin geneHbb-b1 results in the loss of anRsaI site.Mouse Genome (in press).
Konkel, D. A., Maizel, J. V., and Leder, P. (1979). The evolution and sequence of two recently diverged mouse chromosomal β-globin genes.Cell 18865.
Kwok, S., Kellog, D. E., McKinney, N., Spasic, D., Gola, L., Levinson, C., and Sninsky, J. J. (1990). Effects of primer-template mismatches on the polymerase chain reaction: Human immunodeficiency virus type I model studies.Nucl. Acid Res. 18999.
Lee, C. S., Curtis, D., McCarron, M., Love, C., Gray, M., Bender, W., and Chovnick, A. (1987). Mutations affecting expression of therosy locus inDrosophila melanogaster.Genetics 11655.
Lewis, S. E., Johnson, F. M., Skow, L. C., Popp, D., Barnett, L. B., and Popp, R. A. (1985). A mutation in the mouse beta-globin gene detected in the progeny of a female mouse treated with ethylnitrosourea.Proc. Natl. Acad. Sci. USA 825828.
Newton, C. R., Graham, A., Heptinstall, L. E., Powell, S. J., Summers, C., Kalsheker, N., Smith, J. C., and Markham, A. F. (1989). Analysis of any point mutation in DNA: The amplification refractory mutation system, ARMS.Nucl. Acid Res. 172503.
Okayama, H., Curiel, D. T., Brantly, M. L., Holmes, M. D., and Crystal, R. G. (1989). Rapid non radioactive detection of mutations in the human genome by allele specific amplification.J. Lab. Clin. Med. 114105.
Pastinick, A., Vreeken, C., Nivaard, M. J. M., Searles, L. L., and Vogel, E. W. (1989). Sequence analysuis of N-ethyl-N-nitrosourea induced vermillion mutations inDrosophila melanogaster.Genetics 123485.
Peters, J., Andrews, S. J., Loutit, J. F., and Clegg, J. B. (1985). A mouse beta globin mutant that is an exact model of haemoglobin Rainier in man.Genetics 110709.
Peters, J., Jones, J., Ball, S. T., and Clegg, J. B. (1990). Analysis of electrophoretically detected mutations induced in mouse germ cells by ethylnitrosourea.Banbury Report 34: Biology of Mammalian Germ Cell Mutagenesis; p. 247.
Popp, R. A., Bailiff, E. G., Skow, L. C., Johnson, F. M., and Lewis, S. E. (1983). Analysis of a mouse alpha-globin gene mutation induced by ethylnitrosourea.Genetics 105157.
Richardson, K. K., Richardson, F. C., Crosby, R. M., Swenberg, J. A., and Skopek, T. R. (1987). DNA base changes and alkylation followingin vivo exposure ofEscherischia coli to N-methyl-N-nitrosourea or N-ethyla-N-nitrosourea.Proc. Natl. Acad. Sci. USA 84344.
Skow, L. C., Burkhart, B. A., Johnson, F. M., Popp, R. A., Popp, D. M., Goldberg, S. Z., Anderson, W. F., Barnett, L. B., and Lewis, S. E. (1983). A mouse model for β-thalasemia.Cell 341043.
Wu, D. Y., Ugozzoti, L., Pal, B. K., and Wallace, R. B. (1989). Allele specific enzymatic amplification of β-globin genomic DNA for diagnosis of sickle cell anaemia.Proc. Natl. Acad. Sci. USA 862757.
Zdarsky, E., Favor, J., and Jackson, I. J. (1990). The molecular basis ofbrown, an old mouse mutation, and or an induced revertant to wild type.Genetics 126443.
Zielenska, M., Beraneck, D., and Guttenplan, J. B. (1988). Differential mutational profiles induced by N-nitroso-N-ethyl urea: Effect of dose and error prone DNA repair and correlations with DNA adducts.Environ. Mol. Mutagen. 11473.
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Jones, J., Peters, J. The molecular characterization of an A:T to G:C transition in theHbb-b1 gene of the murine homologue of hemoglobin Rainier. Biochem Genet 29, 617–626 (1991). https://doi.org/10.1007/BF02426875
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DOI: https://doi.org/10.1007/BF02426875