Anthropological approach to the heterogeneity of beta-thalassemia mutations in northern Africa.

Results of an epidemiological survey for beta-thalassemic defects involving 239 chromosomes in Algeria are analyzed in relation to the geographic and historical background of the country and are compared with published series for the Tunisian population. Four common mutations account for 81% of the chromosomes, but 13 other defects have been found, illustrating the highly heterogeneous nature of the disease in the northern African countries of the Maghreb. The high frequency of homozygous cases reflects the endogamous social structure of these populations. Distribution of the mutations and linkage to specific RFLP haplotypes provide information concerning their origin and date of introduction in good correlation with the anthropological history of Algeria.

Evolution of the primate beta-globin gene region: nucleotide sequence of the delta-beta-globin intergenic region of gorilla and phylogenetic relationships between African apes and man.

A 6.0-kb DNA fragment from Gorilla gorilla including the 5' part of the beta-globin gene and about 4.5 kb of its upstream flanking region was cloned and sequenced. The sequence was compared to the human, chimpanzee, and macaque delta-beta intergenic region. This analysis reveals four tandemly repeated sequences (RS), at the same location in the four species, showing a variable number of repeats generating both intraspecific (polymorphism) and interspecific variability. These tandem arrays delimit five regions of unique sequence called IG for intergenic. The divergence for these IG sequences is 1.85 +/- 0.22% between human and gorilla, which is not significantly different from the value estimated in the same region between chimpanzee and human (1.62 +/- 0.21%). The CpG and TpA dinucleotides are avoided. CpGs evolve faster than other sequence sites but do not confuse phylogenetic inferences by producing parallel mutations in different lineages. About 75% of CpG doublets have become TpG or CpA since the common ancestor, in agreement with the methylation/deamination pattern. Comparison of this intergenic region gives information on branching order within Hominoidea. Parsimony and distance-based methods when applied to the delta-beta intergenic region provide evidence (although not statistically significant) that human and chimpanzee are more closely related to each other than to gorilla. CpG sites are indeed rich in information by carrying substitutions along the short internal branch. Combining these results with those on the psi eta-delta intergenic region, shows in a statistically significant way that chimpanzee is the closest relative of human.