A multi-perspective view of genetic variation in Cameroon.

In this study, we report the genetic variation of autosomal and Y-chromosomal microsatellites in a large Cameroon population dataset (a total of 11 populations) and jointly analyze novel and previous genetic data (mitochondrial DNA and protein coding loci) taking geographic and cultural factors into consideration. The complex pattern of genetic variation of Cameroon can in part be described by contrasting two geographic areas (corresponding to the northern and southern part of the country), which differ substantially in environmental, biological, and cultural aspects. Northern Cameroon populations show a greater within- and among-group diversity, a finding that reflects the complex migratory patterns and the linguistic heterogeneity of this area. A striking reduction of Y-chromosomal genetic diversity was observed in some populations of the northern part of the country (Podokwo and Uldeme), a result that seems to be related to their demographic history rather than to sampling issues. By exploring patterns of genetic, geographic, and linguistic variation, we detect a preferential correlation between genetics and geography for mtDNA. This finding could reflect a female matrimonial mobility that is less constrained by linguistic factors than in males. Finally, we apply the island model to mitochondrial and Y-chromosomal data and obtain a female-to-male migration Nnu ratio that was more than double in the northern part of the country. The combined effect of the propensity to inter-populational admixture of females, favored by cultural contacts, and of genetic drift acting on Y-chromosomal diversity could account for the peculiar genetic pattern observed in northern Cameroon.

Extended gene diversity at the FMR1 locus and neighbouring CA repeats in a sub-Saharan population.

We report on the allele distributions in a normal black African population at two microsatellite loci neighbouring the FRAXA locus and at the CGG repeat in the 5' end of the FMR-1 gene, which causes the fragile X syndrome. The CGG repeat distribution was found to be similar to that of other ethnic groups, as well as to that of other nonhuman primates, possibly predicting a comparable prevalence of fragile X in Africa. Significant linkage disequilibrium has been observed between fragile X mutations and alleles of the DXS548 and FRAXAC1 loci in European and Asian populations, and some founder chromosomes may be extremely old. Those associated with FRAXAC1-A and DXS548-2 alleles are not present in the Asian fragile X samples. We searched for these alleles and their frequency in the well defined Bamileke population of Cameroon. All previously described alleles and some new ones were found in this sample, supporting the hypothesis of their pre-existence and subsequent loss in Asian populations. Finally, the heterozygosity of the Bamileke sample was significantly higher at both marker loci and comparable to that of Europeans at the CGG repeat, confirming the notion that genetic diversity is greater in Africans than in other groups and supporting the view that evolution of modern man started in Africa.

Anthropological survey on red cell glutathione peroxidase (GPX1) polymorphism in central western Africa: a tentative hypothesis on the interaction between GPX1*2 and Hb beta *S allelic products.

Phenotype and allele frequencies for erythrocyte glutathione peroxidase (GPX1) polymorphism are reported in the Mbugu and Sango (Central African Republic), Goun (Benin), and Bamileke (Cameroon) ethnic groups. The GPX1*2 allele frequencies (from 0.012 in the Sango to 0.058 in the Bamileke) fit into the range of the data already known for the Subsaharan populations. The value of GPX1*2 for study of the genetic admixture between Negro and Pygmy populations is suggested. Three different unusual GPX1 electrotypes are described. Finally, we hypothesize an interaction between GPX1*2 and Hb beta*S allelic products occurring in the sickle cells infected by Plasmodium falciparum.

Blood polymorphism frequencies in the Tofinu, the "Water Men" of Southern Benin.

Informations on the genetic constitution (AcP, EsD, PGM1, AK, 6-PGD, Hb, Hp, Cp and Gc blood systems) of the Tofinu, a lacustrine population living in the pile-work of the Guinean coast (Southern Benin), are reported. The Tofinu gene frequencies are much as would be expected from the geographical position of this country. The AcP, Hp and Hb beta gene frequencies are compared with those of the other ethnic groups of Southern Benin as the Goun, Fon, Djedje, and Nago, using the contingency chi-square test of homogeneity. On the average, the five groups do not show any significant differences. Thus it results that there seems to be a common genetic origin and that the cultural-linguistic differentiation followed the evolutive biological process for the populations of this country.

The AcP polymorphism frequencies in the Mbugu and Sango of Central Africa. (Correlations between the Pr allele frequencies and some climatic factors in Africa).

This paper reports AcP frequencies in the Mbugu and Sango of Central Africa. Among 39 sub-Saharan populations, correlations between Pr allele frequencies and latitude, humidity and altitude indicate that AcP frequencies are significantly correlated with humidity, temperature and altitude. The first-order correlations (constant humidity) diminish by approximately 70% relative to the zero-order correlation.

Further data on the distribution of PGM1 and CAII polymorphisms among the Subsaharan populations (Central African Republic and Benin).

PGM1 and CAII polymorphisms were studied in four population samples of the Central African Republic (Mbugu and Sango) and of Benin (Goun and Nago). The results are compared with those reported on other African populations.

Unusual transferrin TF*D mutants in some Congo populations.

Transferrin allele (TF) distribution was investigated in three Bantu and one Babenga Pygmy groups of Congo, by isoelectric focusing on polyacrylamide (PIEF). In comparison with other Black populations, the four groups had a twofold higher TF*D frequency. Three different TF*D mutants were observed, the commonest type of which was identical by PIEF to a *D1 Caucasian allele. The classification of the other two is discussed. The homozygous TF D1 pattern was present in Babenga. The polymorphism of transferrin confirmed the uniqueness of anthropological traits in such Congo populations.

Frequencies of the GPXT1 (or GPX*2(1) and CA2II alleles in some Congo populations.

Genetic polymorphism of red cell enzyme glutathione peroxidase (GPX1) and carbonic anhydrase (CAII) was investigated in four Congo populations (Beti Bantus, North Bateke and South Bateke Bantus and Babenga Pygmies). All show a polymorphic frequency of the GPXT1 and CA2II alleles, though with a certain variability of values.

Antitrypsin and Gc polymorphisms in some populations of Congo: an unusual, highly frequent mutant, PIS, in Bateke and Babenga.

Four population samples from Congo (Beti and Bateke from Cuvette area, Bateke and Babenga from 'Pool' area) were typed for the electrophoretic mutants of protease inhibitor (PI) and group-specific component (Gc), as part of a general survey on the genetic structure of these ethnic groups. An unusual PI mutant (tentatively called PIS*) had a singularly high frequency in the Bateke and the Babenga. Data shown here will help in ascertaining whether genetic differentiation could exist in Congolese populations.

EsD in Negro and Caucasian populations: is the EsD5 a 'Caucasian allele'?

A total of 461 individuals, belonging to some Subsaharan populations (Beti, Bateke and Babenga Pygmies of Congo; Goun and Nago of Benin; Mbugu and Sango of the Central African Republic), and a sample of 231 individuals of the population of Rome (Italy) have been typed for red cell esterase D using conventional electrophoresis and isoelectric focusing. The Subsaharan populations showed a high variability of the frequency of the EsD2 allele (0.018-0.138) and the absence of the EsD5 allele which, on the contrary, reached a polymorphic frequency (0.017) in the Italian sample. These results suggest that the EsD5 allele has a Caucasian origin.

An MspI polymorphism in the X-specific region proximal to the pseudoautosomal boundary. A new example of a unique "African" marker?

A polymorphic MspI site was located in the X-specific region proximal to the pseudoautosomal boundary. Two alleles defined by the absence or the presence of the MspI site were detected by the polymerase chain reaction (PCR) in a sample of Bantu-speaking individuals from Cameroon. No variation for this site was observed in a population sample from Italy.

The peopling of sub-Saharan Africa: the case study of Cameroon.

This study analyzes the distribution of ten protein genetic polymorphisms in eighteen populations from the most densely inhabited areas of Cameroon. The languages spoken belong to three different linguistic families [Afro-Asiatic (AA), Nilo-Saharan (NS) and Niger-Kordofanian (NK)]. The analysis of variation of allele frequencies indicates that the level of genetic interpopulation differentiation is rather low (F(st) = 0.011 +/- 0.006) but statistically significant (p < 0.001). This result is not unexpected because of the relatively small geographic area covered by our survey. This value is also significantly lower than the one estimated for other groups of African populations. Among the factors responsible for this, we discuss the possible role of gene flow. There is a considerable genetic differentiation among the AA populations of north Cameroon as is to be expected because they all originated from the first agriculturists of the farming "savanna complex." The Podowko and Uldeme are considerably different from all the other AA groups, probably due to the combined effect of genetic drift and isolation. In the case of the Wandala and Massa, our analyses suggest that genetic admixture with allogeneous groups (especially with the Kanuri) played an important role in determining their genetic differentiation from other AA speaking groups. The Bantu speaking populations (Bakaka, Bamileke Bassa and Ewondo, NK family, Benué Congo subfamily) settled in western and southern Cameroon are more tightly clustered than AA speaking groups. This result shows that the linguistic affinity among these four populations coincides with a substantial genetic similarity despite their different origin. Finally, the Fulbe are genetically distinct from all the populations that belong to their same linguistic phylum (NK), and closer to the neighboring Fali and Tupuri, eastern Adamawa speaking groups of north Cameroon.

Brief communication: Resistance to Falciparum malaria in alpha-thalassemia, oxidative stress, and hemoglobin oxidation.

A recent survey conducted on Vanuatu Island suggests that resistance to Plasmodium falciparum in alpha-thalassemic individuals may have an immunological basis. This study is important since it seems to undermine the current idea that red-cell genetic defects give protection against falciparum malaria by reducing intraerythrocytic growth and development of the parasite. However, the mechanisms underlying these clinical and genetic observations are not yet fully understood. Based on a review of the relevant literature, we first show that the model based on the interaction between hemoglobin (Hb) and membrane components may provide a molecular basis for the involvement of the immune response in genetic adaptation to malaria. Second, we discuss the main evolutionary implications of the model. Finally, we suggest two approaches by which anthropological studies could provide a useful way of testing the model: 1) analysis of the interactions of malaria-resistance genes with genetic polymorphisms which affect the erythrocyte redox status and 2) study of the antimalarial effects of natural products (introduced as a part of a diet or for traditional antimalarial therapy) capable of interfering with the Hb/membrane interaction.

Genetic studies in Cameroon: mitochondrial DNA polymorphisms in Bamileke.

In two population samples of 77 Bamileke (Bantu sensu lato) and 18 Bakaka (Bantu sensu stricto) from southwestern Cameroon, the mtDNA RFLPs for the HpaI, HaeII, MspI, AvaII, and HincII enzymes were studied. Two of the MspI morphs had not been reported before. Six new types were found, four of which represent new combinations of previously described morphs. The AvaII morph 3 was found in association with the "African" HpaI morph 3. This finding is in line with previous observations in Negroids and demonstrates the usefulness of this combination as an indicator of black African ancestry. Two differences were noted between the groups: a lower frequency of HpaI morph 3 and a higher frequency of HaeII morph 4 in the Bakaka with respect to the Bamileke (0.44 versus 0.62 and 0.17 versus 0.03, respectively). The importance of these differences could not be evaluated because the Bakaka sample was too small. Nevertheless, because the Bamileke show a relatively low frequency of mtDNA type 1 (2.1.1.1.-) and high frequencies of mtDNA types 2 (3.1.1.1.3.-) and 7 (3.1.1.1.1.-), they can be placed with the other Negroids so far examined, but they are closer to the Senegalese than to the Bantu from South Africa. In comparing the Bamileke and the Bantu, mtDNA type 3 (3.1.1.2.2.-) appears particularly discriminative because it is present in all the Bantu subgroups examined but not in the Bamileke. mtDNA type 39 (2.1.4.1.1.-), which was observed only in the Bamileke, might be considered likewise discriminative, although to a lesser degree.

Population genetics of red cell and serum markers in the four Albanian communities of Molise, Italy.

In this paper phenotype and gene frequencies of ten genetic markers (AK, AP, EsD, 6-PGD, PGM1, PGM2, Hb, Alb, Cp and Hp) of the four Albanian communities (Campomarino, Montecilfone, Portocannone and Ururi) living in Molise are reported. The gene frequencies show a high variability. The heterogeneity analysis among these villages could demonstrate significant differences between Campomarino and Montecilfone and between Campomarino and Ururi. It is interesting to note that the demographic analysis has shown the highest rate of immigration and the lowest percentages of endogamy, Albanian surnames and Albanian-speaking individuals in Campomarino. Against that Montecilfone and Ururi are showing opposite values for the same parameters. The genetic data are also indicating some differences between these Albanian communities and the Italian population. A comparison with the present population of Albany is not possible because of the lack of data.

A bio-anthropological study on the Bakakas of Cameroon.

Bakakas are native Bantus belonging to the Mbo-Bakossi group, peopling the Cameroon's Littoral region. In the context of a wide bio-anthropological study project focused on the bio-historical processes involved in the areas, 278 adults of both sexes from the villages of Ebone and Bakwat (Bakaka Canton) were investigated for 14 erythrocyte and serum genetic polymorphisms (ACP1, ADA, EsD, GLO, Hb beta, GPX1, CAII, PGM1, SAHH, 6-PGD, Hp, Pi, Gc and Tf). With only a few exceptions (Hp and GLO systems), the genetic frequencies of the polymorphisms considered tend to fall within the range of variation known for the subsaharan populations. With reference to the malaria endemicity characterizing the Littoral environment, high frequencies for Hb beta*S allele and absence of the ACP1*R 'Negro allele' were recorded. The genetic distances among Bakakas and 14 other Central African populations were also calculated from six genetic loci.

Testing a biochemical model of human genetic resistance to falciparum malaria by the analysis of variation at protein and microsatellite loci.

We recently proposed a biochemical model of genetic resistance to falciparum malaria based on the role of oxidant stress (of parasitic origin) in inducing the irreversible oxidation of hemoglobin and its binding to the erythrocyte membrane (Destro-Bisol et al. 1996). To test the model, we analyzed the relationships between the polymorphisms at the hemoglobin beta chain (HBB) and red cell glutathione peroxidase (GPX1) loci in 18 populations that had been subjected to endemic malaria (Cameroon and Central African Republic). The erythrocytes of GPX1*2 heterozygotes should be more efficient in sheltering the cell membrane from irreversible oxidation and binding of hemoglobin caused by the oxidant stress exerted by Plasmodium falciparum. According to our model, the GPX1*2 allele has an epistatic effect on the HBB*A/*S genotype by lowering its protection against falciparum malaria. In turn, this should decrease the fitness of the HBB*A/*S-GPX1*2/*1 genotype. Our predictions were confirmed. In fact, we observed a clear trend toward a dissociation between the HBB*A/*S and GPX1*2/*1 genotypes in the overall data. To test alternative hypotheses, we also analyzed the genetic variation at 9 protein and 10 autosomal microsatellite loci at both the single- and the 2-locus level. We also discuss the possible relevance of an alternative biochemical pathway. The results further support the conclusions of our study because the dissociation between the GPX1*2/*1 and HBB*A/*S genotypes does not appear to be related either to a general decrease in heterozygosity or to an increased risk of sudden death in HBB*A/*S individuals.

Genetic variation at the ApoB 3'HVR, D2S44, and D7S21 loci in the Ewondo Ethnic Group of Cameroon.

A sample of the Ewondo population (a Bantu-speaking group of Southern Cameroon) was analyzed for the polymorphism at three tandem repeated DNA loci (ApoB 3' HVR, D2S44, and D7S21). We observed a greater number of ApoB 3' HVR alleles (17) and a significantly higher estimated heterozygosity (.879 +/- .011) than in previously surveyed populations, with the exception of U.S. Blacks. The higher genetic variability of Ewondo and U.S. Blacks was also shown by the ApoB 3' HVR allele-frequency spectra. A method for measuring population distances, based on cumulative fragment-size distribution, is described. Interpopulation comparisons for ApoB 3' HVR were carried out by this method and were compared with those obtained by a genetic distance measurement. The two sets of results showed a consistent pattern of population differentiation: the Ewondos and the U.S. Blacks clustered together and were well apart from both a Caucasian cluster (Swedes, U.S. Whites, Italians, and Germans) and other well-defined populations (Sikhs of India and Pehuence Indians of Chile). Profile distances were then computed from D2S44 and D7S21 bined data. This analysis indicated a genetic affinity between Ewondos, U.S. Blacks, and Afro-Caribbean Blacks and outlined the genetic diversity between Ewondos, Caucasians, and Asian Indians.

Microsatellite variation in Central Africa: an analysis of intrapopulational and interpopulational genetic diversity.

As a part of a research project on molecular variation in Central Africa, we have analyzed 10 microsatellites (CD4, CSFO, D3S1358, D18S51, D21S11, F13A1, FES, TH01, TPOX, and VWA) in the Bamileke and Ewondo from Cameroon and the Sanga and Mbenzele Pygmies from the Central African Republic (a total of 390 chromosomes). A statistically significant trend towards heterozygote deficiency was detected in the Mbenzele Pygmies. This was established through the use of powerful exact tests for the Hardy-Weinberg equilibrium. A certain degree of isolation and a small effective size may explain this finding. However, the lack of any substantial reduction in allelic diversity in the Mbenzele does not support the possibility that this group has a smaller effective size in evolutionary terms. A possible explanation based on ethnographic studies suggests that the gene flow from non-Pygmies to Pygmies could have been interrupted only in relatively recent times. The analysis of association between genotypes at pairs of independent loci indicates that the level of subheterogeneity is markedly lower in the Bamileke than in other sampled populations. This may be explained by the combined effect of larger population size, more rigid respect of clanic exogamy, and higher matrimonial mobility of the Bamileke. Finally, we have analyzed interpopulational relationships among our sampled populations and other Central African populations. The results are consistent with a previous study of protein loci (Spedini et al. 1999), which suggests the recent history of the Bamileke and Ewondo has led them to aquire a substantial genetic similarity. Furthermore, the Mbenzele Pygmies diverge from Biaka Pygmies, despite their common origin and geographical proximity. This is probably due to the differentiating effect of genetic drift, which is enhanced by the small effective size of Pygmy populations.