Two ethnic-specific polymorphisms in the human beta pseudogene of hemoglobin

FIORENZA POMPEI, BIANCA MARIA CIMINELLI, AND GUIDO MODIANO

Abstract Two polymorphic sites, -107 C -> T and -100 G -> C with respect to the cap site of the human beta pseudogene of the hemoglobin gene, are described. They have been studied in five European, one Indian, two Asian, and two sub-Saharan African populations. The -107 C -> T site turned out to be polymorphic in all five European populations and the Indian population (pooled q = 0.142 +/- 0.018) and in the two Asian populations (pooled q = 0.073 +/- 0.025), but it was monomorphic in the two sub-Saharan populations. On the contrary, the -100 G -> C site was polymorphic in the two sub-Saharan samples (q = 0.093 +/0.024), but the variant allele was not found in any of the European, Indian, or Asian samples. Thus this only 8-bp-long stretch of DNA is informative for estimating the extent of genetic admixture in sub-Saharan Africans.

KEY WORDS: DNA POLYMORPHIC SITES, DISCRIMINATORY ANTHROPOGENETIC MARKERS, SUB-SAHARAN AFRICANS, HAPLOTYPES

Genetic polymorphisms are a potential tool for traditional physical anthropology. The discovery and full understanding of a genetic polymorphism from the formal and molecular points of view are not sufficient to make it a real rather than just a potential anthropogenetic tool. To achieve this new status, one must determine the allele frequencies in an adequate number of appropriately selected human groups. All randomly chosen and apparently neutral genetic polymorphisms can be used to evaluate the degree of diversification among the populations under study in terms of mean genetic distances and to identify the principal components of variation and their geographic direction [see, for example, Menozzi et al. (1978)].

A further aim of anthropology, which may be pursued through an adequate exploitation of genetic polymorphisms, is the evaluation of the degree of genetic admixture between groups and, more precisely, the relative contributions of two different gene pools to the gene pool of a mixed group. The best known example is the estimate of the European component in the present US black gene pool. Clearly, for this purpose the suitable anthropogenetic markers are different from those used to evaluate the mean genetic distances. In fact, the anthropogenetic markers needed to obtain gene flow estimates should not be randomly chosen. They should instead be selected according to the degree of diversification among the groups under study: the higher the diversification, the better the marker. Furthermore, if the donor's and the recipient's gene frequencies are different, gene flow to group A (the recipient) from group B (the donor) can be best appreciated if the informative marker is more common in group B than in group A (ideally, if it is present only in group B) rather than vice versa.

Irrespective of its possible anthropological use (as a random or as a selected anthropogenetic marker), a preliminary sine qua non condition must be fulfilled in order for a genetic polymorphism to be exploitable for anthropological purposes: The marker must be studied in an adequate number of different human groups.

Since the 1920s, when a genetic marker (the ABO system) was first used in anthropology (Hirszfeld and Hirszfeld 1919), and until the end of the 1970s only a few genetic polymorphisms were known. From the 1920s to the end of the 1950s these polymorphisms consisted of essentially 10 blood group systems [see Mourant (1954), Race and Sanger (1958), and Giblett (1969)]; later, the number expanded to approximately 20 protein polymorphisms, including HLA and GM [see Mourant et al. (1976), Nei and Roychoudhury (1982), Tills et al. (1983), and Cavalli-Sforza et al. (1994)]. During these 60 years the discovery of a new polymorphism was an important event for both geneticists and anthropologists, and to fully exploit their potential anthropological usefulness, laboratories specializing in one or a few populations rather than in selected markers adequately studied substantially all the few thenknown polymorphisms.

Fifteen years have been sufficient to completely turn upside down the process of slowly identifying new genetic polymorphisms and exploiting them one by one exhaustively for anthropology. Since the beginning of the 1980s about 15,000 genetic polymorphisms have been identified (essentially all at the DNA level). However, just when the potential new tools for anthropogenetic research were becoming far more numerous than anyone would have dared to hope for until only a few years earlier, their applications use for genome mapping (Human Genome Project) greatly overwhelmed their use in anthropology. Thus the number of good anthropogenetic markers (i.e., genetic markers studied on an adequate number of different populations, each represented by an adequately large sample) increased during the last decade with a pace orders of magnitude slower than the rate of discovery of the markers themselves.

Furthermore, this worldwide trend of not performing the work required to transform a genetic marker into a more or less discriminatory anthropogenetic marker (i.e., into a marker with a high FsT) has been taking place during the last, presumably short, period while progressively higher gene flows completely blur the distinctions between human groups.