title: Is the doubly deleted alpha-thalassemia gene a "fugitive" allele?
abstract: The alpha-thalassemias (particularly in Asia) can be considered as a three-allele system, with one "normal" allele (N) consisting of a pair of closely linked alpha-chain loci, a second "single" allele (S) in which one of the loci has been lost by deletion, and a third "double" allele (D) in which both have been lost. Representatives of all the sets of fitnesses leading to the maintenance of this condition by selection for malaria resistance have been explored, and after the discarding of unlikely sets of fitnesses, it is found that there will be three outcomes: (1) the S chromosome is fixed, (2) the S and N chromosomes form a stable polymorphism, and (3) the N and D chromosomes form a stable polymorphism, but this can be lost and the population forced to fixation by the introduction of sufficiently large number of S chromosomes. Some Melanesian populations appear to have reached outcome (1), while frequencies in African, Mediterranean, and Middle Eastern populations are not incompatible with outcome (2). Southeast Asian populations, however, which carry S and D chromosomes in high frequency, may be in a state of flux. The D chromosome may form a polymorphism with N locally, but it can be driven from the local population by the introduction of large numbers of S chromosomes. The D chromosome would thus be somewhat analogous to a fugitive species, which can only exist in certain transient environments and is displaced as the environment changes. The possibility that N, S, and D are coexisting as a stable polymorphism can almost certainly be ruled out by a consideration of fitness sets required.
mesh_terms: D000483:Alleles; D044466:Asian People; D044383:Black People; D002872:Chromosome Deletion; D004198:Disease Susceptibility; D005006:Ethnicity; D005787:Gene Frequency; D005796:Genes; D005914:Globins / Q000235:genetics*; D006801:Humans; D008288:Malaria; D011110:Polymorphism, Genetic; D012641:Selection, Genetic; D013789:Thalassemia / Q000235:genetics*; D044465:White People
chemical_list: D005914:Globins