Abstract
Human genetic disorders provide an extraordinary richness of data on the diversity of defective alleles. Well over 100 defective alleles for each of several human genetic disorders have been identified, including breast cancer (BRCA1), cystic fibrosis (CFTR), muscular dystrophy (DZM), and phenylketonuria (PAH). These observations raise the classical question of balance between the action of mutation generating new defective alleles and selection removing those alleles from the population. The problem of multiple-allele, mutation-selection balance was considered by Crow and Kimura, who obtained some approximate results showing that the level of dominance and degrees of interallelic complementation are important in determining the equilibrium allele frequencies. Here those deterministic results are reviewed and extended, showing that there are conditions yielding surprisingly high equilibrium frequencies of defective alleles. Just as the equilibrium mutation load is independent of the level of dominance, it is also independent of the number of defective alleles.
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References
Bertranpetit, J. & F. Calafell, 1996. Genetic and geographical variability in cystic fibrosis: evolutionary considerations, pp. 97–118 in variation in the human genome. Wiley, Chichester.
Crow, J.F. & M. Kimura, 1964. The theory of genetic loads. Proc. Xlth Int. Congr. Genet. 2: 495–505.
Crow, J.F. & C. Denniston, 1985. Mutation in human populations. Adv. Hum. Genet. 14: 59–123.
Crow, J.F. & M. Kimura, 1970. An Introduction to Population Genet ic Theory. Harper and Row, New York.
Gabriel, S.E., K.N. Brigman, B.H. Koller, R.C. Boucher & M.J. Stutts, 1994. Cystic fibrosis heterozygote resistance to cholera toxin in the cystic fibrosis mouse model. Science 266: 107–109.
Goltsov, A.A., R.C. Eisensmith, D.S. Konecki, U. Lichter-Konecki & S.L.C. Woo, 1992. Associations between mutations and a VNTR in the human phenylalanine hydroxylase gene. Am. J. Hum. Gen. 51: 627–636.
Haidane, J.B.S., 1937. The effect of variation on fitness. Am. Nat. 71: 337–349
Hartl, D.L. & R.B. Campbell, 1982. Allele multiplicity in simple mendelian disorders. Am. J. Hum. gen. 34: 866–873.
Lange, K. & R.Z. Fan, 1997. Branching process models for mutant genes in nonstationary populations. Theor. Pop. Biol. 51: 118–133.
Okano, Y, R.C. Eisensmith, F. Guttler, U. Lichter-Konecki, D.S. Konecki, F.K. Tretz, M. Dasovich, T. Wang, K. Henriksen & H. Lou, 1991. Molecular basis of phenotypic heterogeneity in phenylketonuria. New Eng. J. Med. 324: 1232–1238.
Scriver, C.R., S. Kaufman & S.L. Woo, 1988. Mendelian hyper-phenylalaninemia. Ann. Rev. Genet. 22: 301–321.
Tishkoff, S.A., E. Dietzsch, W. Speed, A.J. Pakstis, J.R. Kidd, K. Cheung, B. Bonné-Tamir, A.S. Santachiara-Benerecetti, P. Moral. M. Krings, S. Pääbo, E. Watson, N. Risch, T. Jenkins & K.K. Kidd, 1996. Global patterns of linkage disequilibrium at the CD4 locus and modern human origins. Science 271: 1380–1387.
Wright, S., 1937. The distribution of gene frequencies in populations. Proc. Natl. Acad. Sci. USA 23: 307–320.
Zielenski, J. & L.-C. Tsui, 1995. Cystic fibrosis: genotypic and phenotypic variations. Ann. Rev. Genet. 29: 777–807.
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© 1998 Springer Science+Business Media Dordrecht
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Clark, A.G. (1998). Mutation-selection balance with multiple alleles. In: Woodruff, R.C., Thompson, J.N. (eds) Mutation and Evolution. Contemporary Issues in Genetics and Evolution, vol 7. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-5210-5_4
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DOI: https://doi.org/10.1007/978-94-011-5210-5_4
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