Hassen Chaabani

Mixed origin of the current Tunisian population from the analysis of Alu and Alu /STR compound systems

During successive historical periods, Tunisia has been a crossroads of multiple civilizations and their corresponding key population movements. The aim of this study was to provide genetic information relating to the mixed origin of the Tunisian population, and to analyze its genetic relationship with other North African and Mediterranean populations. A set of 16 Alu and 3 Alu/STR compound systems has been analyzed in 268 autochthonous Tunisians from the north-center and the south of the country. Our two sampled populations showed no significant differentiation from one another in any of the three Alu/STR compound systems, whereas the analysis of the 16 Alu markers revealed a significant genetic differentiation between them. A sub-Saharan component shown by the three Alu/STR combinations is more noticeable in our north-center sample than in that of the south. The presence of two Alu/STR combinations specific to North African ancestral populations also suggests that the ancient Berber component is relatively more substantial in the north and center regions than in the south. Our Tunisian samples cluster together with other Berber samples from Morocco and Algeria, underpinning the genetic similarity among North Africans regardless of their current linguistic status (Berber or Arabic).

New insights into the genetic history of Tunisians: data from Alu insertion and apolipoprotein E gene polymorphisms.

Background: Among polymorphisms of non-transcribed DNA sequences and functional genes, those of Alu insertions and that of the APOE gene have been widely used to clarify the degree of genetic relationships between human populations. Aim: APOE gene and eight Alu insertion polymorphisms were investigated in Tunisians and compared with data from neighbour populations in order to gain new insights into the genetic position of Tunisia in the Mediterranean region. Subjects and methods: A total of 121 individuals from the North and Centre-South regions were sampled. Results: No significant genetic differences were found between Tunisians and North Africans when samples representative of wide areas were considered. APOE gene variation seemed slightly less powerful than the Alu polymorphisms in detecting North–South Mediterranean differences. Conclusion: North African populations show a substantial degree of genetic homogeneity, which may reflect the similarity of their origins, mainly when samples from large geographical areas are compared. The relative genetic homogeneity of the whole Mediterranean region probably reflects a common origin and/or remarkable levels of gene flow. However, this gene flow has not yet erased the differentiation between the two Mediterranean shores, as revealed by Alu insertion polymorphisms.

The X chromosome Alu insertions as a tool for human population genetics: data from European and African human groups.

Alu elements are the most abundant mobile elements in the human genome (∼1 100 000 copies). Polymorphic Alu elements have been proved to be useful in studies of human origins and relationships owing to two important advantages: identity by descent and absence of the Alu element known to be the ancestral state. Alu variation in the X chromosome has been described previously in human populations but, as far as we know, these elements have not been used in population relationship studies. Here, we describe the allele frequencies of 13 ‘young’ Alu elements of the X chromosome (Ya5DP62, Ya5DP57, Yb8DP49, Ya5a2DP1, Yb8DP2, Ya5DP3, Ya5NBC37, Yd3JX437, Ya5DP77, Ya5NBC491, Yb8NBC578, Ya5DP4 and Ya5DP13) in six human populations from sub-Saharan Africa (the Ivory Coast), North Africa (Moroccan High Atlas, Siwa oasis in Egypt, Tunisia), Greece (Crete Island) and Spain (Basque Country). Eight out of 13 Alu elements have shown remarkably high gene diversity values in all groups (average heterozygosities: 0.342 in the Ivory Coast, 0.250 in North Africa, 0.209 in Europe). Genetic relationships agree with a geographical pattern of differentiation among populations, with some peculiar features observed in North Africans. Crete Island and the Basque Country show the lowest genetic distance (0.0163) meanwhile Tunisia, in spite of its geographical location, lies far from the other two North African samples. The results of our work demonstrate that X chromosome Alu elements comprise a reliable set of genetic markers useful to describe human population relationships for fine-scale geographical studies.

Apolipoprotein gene polymorphisms and plasma levels in healthy Tunisians and patients with coronary artery disease

AimTo analyze apolipoprotein gene polymorphisms in the Tunisian population and to check the relation of these polymorphisms and homocysteine, lipid and apolipoprotein levels to the coronary artery disease (CAD).MethodsIn healthy blood donors and in patients with CAD complicated by myocardial infarction (MI) four apolipoprotein gene polymorphisms [APO (a) PNR, APO E, APO CI and APO CII] were determined and plasma levels of total homocysteine, total cholesterol (TC), triglycerides (TG), HDL-cholesterol (HLD-C) and apolipoproteins (apo A-I, Apo B, Apo E) were measured.ResultsAnalysis of the four apolipoprotein gene polymorphisms shows a relative genetic homogeneity between Tunisian population and those on the other side of Mediterranean basin. Compared to controls, CAD patients have significantly higher main concentrations of TC, TG, LDL-C, apo B and homocysteine, and significantly lower ones of HDL-C, apo A-I and apo E. The four apolipoprotein gene polymorphisms have not showed any significant differences between patients and controls. However, the APO E4 allele appears to be associated to the severity of CAD and to high levels of atherogenic parameters and low level of apo E, which has very likely an anti-atherogenic role.ConclusionAlthough APO (a) PNR, APO CI and APO CII genes are analyzed in only few populations, they show a frequency distribution, which is not at variance with that of APO E gene and other widely studied genetic markers. In the Tunisian population the APO E 4 appears to be only indirectly involved in the severity of CAD. In the routine practice, in addition of classic parameters, it will be useful to measure the concentration of apo E and that of Homocysteine and if possible to determine the APO E gene polymorphism.

Ethnic composition and genetic differentiation of the Libyan population: insights on Alu polymorphisms

Abstract Background: It is thought that the ancient population of Libya was mainly composed of Saharan Berbers. Socio-geographic conditions and historical events have exerted some changes on the composition of the present-day Libyan population. Aim: To screen a set of autosomal Alu markers in a representative sample of the general Libyan population in order to study its ethnic and genetic structure and to re-examine its genetic relationships with Mediterranean and Middle Eastern groups. Subjects and methods: A sample of 190 Libyans was analysed for 17 Alu insertions. The sample was divided according to the Arabic or Berber origin of individuals’ surnames. Results: The current general Libyan population is homogeneous and shows considerable genetic diversity compared with other North Mediterranean and North African populations. It shows intermediate genetic distances between Moroccans, Algerians and Tunisians on one side and Egyptian Siwa Berbers on the other. No particular affinities with Middle Eastern groups were detected. Conclusion: Alu insertions are useful markers to contribute to the reconstruction of human population history at a microgeographic scale, in particular when the analyses include anthropologically well sampled populations. The present results provide new information to improve understanding some aspects of the complex peopling of North Africa.

Different Evolutionary Histories of the Coagulation Factor VII Gene in Human Populations

Immoderate blood clotting constitutes a risk factor for cardiovascular disease in modern industrialised societies, but is believed to have conferred a survival advantage, i.e. faster recovery from bleeding, on our ancestors. Here, we investigate the evolutionary history of the Coagulation Factor VII gene (F7) by analysing five cardiovascular‐risk‐associated mutations from the F7 promoter and nine neutral polymorphisms (six SNPs and three microsatellites) from the flanking region in 16 populations from the broader Mediterranean region, South Saharan Africa and Bolivia (687 individuals in total). Population differentiation and selection tests were performed and linkage disequilibrium patterns were investigated. In all samples, no linkage disequilibrium between adjacent F7 promoter mutations −402 and −401 was observed. No selection signals were detected in any of the samples from the broader Mediterranean region and South Saharan Africa, while some of the data suggested a potential signal of positive selection for the F7 promoter in the Native American samples from Bolivia. In conclusion, our data suggest, although do not prove, different evolutionary histories in the F7 promoter region between Mediterraneans and Amerindians.

Genetic position of Bahrain natives among wider Middle East populations according to Alu insertion polymorphisms

Background: The genetic differentiation of Bahrain natives is unclear because of the absence of adequate genetic studies. Aim: Eight Alu insertion polymorphisms have been analysed in Bahrainis and southern Iranians to examine the origins of Bahrainis and to determine their genetic position among wider Middle East populations. Subjects and methods: Two representative samples of 97 Bahrainis and 65 southern Iranians have been determined. Genetic relationships among populations have been estimated by a principal component plot based on the R-matrix software. Mantel tests have been used to check the statistical significance of correlation between genetic and geographic distances. Results: The results show that Bahrainis are in an intermediate genetic position between Emirians and Southern Iranians. Although a general significant correlation between genetic and geographic distances was found between the 16 populations included in the analysis, a lack of this correlation may occur in some particular situations such as the case of populations from southern Iran, United Arab Emirates (UAE) and Bahrain, separated by the Persian Gulf. Conclusion: The results support the idea that Bahrainis ancestors were mainly emigrants from Arabia and Iran. In addition the results show that the Iranian component may reach 69.2% of the current genetic pool of Bahrainis.

Analysis of Genomic Regions Associated With Coronary Artery Disease Reveals Continent-Specific Single Nucleotide Polymorphisms in North African Populations

Background In recent years, several genomic regions have been robustly associated with coronary artery disease (CAD) in different genome-wide association studies (GWASs) conducted mainly in people of European descent. These kinds of data are lacking in African populations, even though heart diseases are a major cause of premature death and disability. Methods Here, 384 single nucleotide polymorphisms (SNPs) in the top four CAD risk regions (1p13, 1q41, 9p21, and 10q11) were genotyped in 274 case-control samples from Morocco and Tunisia, with the aim of analyzing for the first time if the associations found in European populations were transferable to North Africans. Results The results indicate that, as in Europe, these four genetic regions are also important for CAD risk in North Africa. However, the individual SNPs associated with CAD in Africa are different from those identified in Europe in most cases (1p13, 1q41, and 9p21). Moreover, the seven risk variants identified in North Africans are efficient in discriminating between cases and controls in North African populations, but not in European populations. Conclusions This study indicates a disparity in markers associated to CAD susceptibility between North Africans and Europeans that may be related to population differences in the chromosomal architecture of these risk regions.

Geographical and social influences on genetic diversity within the Egyptian population: analyses of Alu insertion polymorphisms

Abstract Background: The geographical location of Egypt at the crossroads of several major cultural areas between North Africa and the Middle East has contributed to its population history. Aim: To analyse the genetic structure of the population living in two geographical parts of Egypt. Subjects and methods: A sample of 112 Egyptians from the North African part of Egypt (Ismailia sample) and a sample of 52 Egyptians from the Asian part Sinai, have been analysed using 10 Alu insertion polymorphisms. Results: The results of the present study showed a significant genetic difference between the Sinai and Ismailia samples. The latter showed an evident genetic affinity with North African populations; whereas the Sinai sample was found to be genetically closer to the Middle East populations. The Sinai sample showed a low average heterozygosity, unlike that found in the Ismailia sample. Conclusion: This study provides new insights into the genetic structure of the Egyptian population living in a land bridge between Africa and Asia. Results suggest a genetic discontinuity between the Sinai population and that of the North African part of Egypt. This discontinuity would have been maintained thanks to geo-climatic and social factors.

Research of the origin of a particular Tunisian group using a physical marker and Alu insertion polymorphisms

The aim of this study was to show how, in some particular circumstances, a physical marker can be used along with molecular markers in the research of an ancient people movement. A set of five Alu insertions was analysed in 42 subjects from a particular Tunisian group (El Hamma) that has, unlike most of the Tunisian population, a very dark skin, similar to that of sub-Saharans, and in 114 Tunisian subjects (Gabes sample) from the same governorate, but outside the group. Our results showed that the El Hamma group is genetically midway between sub-Saharan populations and North Africans, whereas the Gabes sample is clustered among North Africans. In addition, The A25 Alu insertion, considered characteristic to sub-Saharan Africans, was present in the El Hamma group at a relatively high frequency. This frequency was similar to that found in sub-Saharans from Nigeria, but significantly different from those found in the Gabes sample and in other North African populations. Our molecular results, consistent with the skin color status, suggest a sub-Saharan origin of this particular Tunisian group.