Karima Fadhlaoui-Zid

Genomic Ancestry of North Africans Supports Back-to-Africa Migrations

North African populations are distinct from sub-Saharan Africans based on cultural, linguistic, and phenotypic attributes; however, the time and the extent of genetic divergence between populations north and south of the Sahara remain poorly understood. Here, we interrogate the multilayered history of North Africa by characterizing the effect of hypothesized migrations from the Near East, Europe, and sub-Saharan Africa on current genetic diversity. We present dense, genome-wide SNP genotyping array data (730,000 sites) from seven North African populations, spanning from Egypt to Morocco, and one Spanish population. We identify a gradient of likely autochthonous Maghrebi ancestry that increases from east to west across northern Africa; this ancestry is likely derived from “back-to-Africa” gene flow more than 12,000 years ago (ya), prior to the Holocene. The indigenous North African ancestry is more frequent in populations with historical Berber ethnicity. In most North African populations we also see substantial shared ancestry with the Near East, and to a lesser extent sub-Saharan Africa and Europe. To estimate the time of migration from sub-Saharan populations into North Africa, we implement a maximum likelihood dating method based on the distribution of migrant tracts. In order to first identify migrant tracts, we assign local ancestry to haplotypes using a novel, principal component-based analysis of three ancestral populations. We estimate that a migration of western African origin into Morocco began about 40 generations ago (approximately 1,200 ya); a migration of individuals with Nilotic ancestry into Egypt occurred about 25 generations ago (approximately 750 ya). Our genomic data reveal an extraordinarily complex history of migrations, involving at least five ancestral populations, into North Africa.

Mitochondrial DNA heterogeneity in Tunisian Berbers.

Berbers live in groups scattered across North Africa whose origins and genetic relationships with their neighbours are not well established. The first hypervariable segment of the mitochondrial DNA (mtDNA) control region was sequenced in a total of 155 individuals from three Tunisian Berber groups and compared to other North Africans. The mtDNA lineages found belong to a common set of mtDNA haplogroups already described in North Africa. Besides the autochthonous North African U6 haplogroup, a group of L3 lineages characterized by the transition at position 16041 seems to be restricted to North Africans, suggesting that an expansion of this group of lineages took place around 10500 years ago in North Africa, and spread to neighbouring populations. Principal components and the coordinate analyses show that some Berber groups (the Tuareg, the Mozabite, and the Chenini‐Douiret) are outliers within the North African genetic landscape. This outlier position is consistent with an isolation process followed by genetic drift in haplotype frequencies, and with the high heterogeneity displayed by Berbers compared to Arab samples as shown in the AMOVA. Despite this Berber heterogeneity, no significant differences were found between Berber and Arab samples, suggesting that the Arabization was mainly a cultural process rather than a demographic replacement.

Analysis of the HLA population data (AHPD) submitted to the 15th International Histocompatibility/Immunogenetics Workshop by using the Gene[rate] computer tools accommodating ambiguous data (AHPD project report)

During the 15th International Histocompatibility and Immunogenetics Workshop (IHIWS), 14 human leukocyte antigen (HLA) laboratories participated in the Analysis of HLA Population Data (AHPD) project where 18 new population samples were analyzed statistically and compared with data available from previous workshops. To that aim, an original methodology was developed and used (i) to estimate frequencies by taking into account ambiguous genotypic data, (ii) to test for Hardy-Weinberg equilibrium (HWE) by using a nested likelihood ratio test involving a parameter accounting for HWE deviations, (iii) to test for selective neutrality by using a resampling algorithm, and (iv) to provide explicit graphical representations including allele frequencies and basic statistics for each series of data. A total of 66 data series (1-7 loci per population) were analyzed with this standard approach. Frequency estimates were compliant with HWE in all but one population of mixed stem cell donors. Neutrality testing confirmed the observation of heterozygote excess at all HLA loci, although a significant deviation was established in only a few cases. Population comparisons showed that HLA genetic patterns were mostly shaped by geographic and/or linguistic differentiations in Africa and Europe, but not in America where both genetic drift in isolated populations and gene flow in admixed populations led to a more complex genetic structure. Overall, a fruitful collaboration between HLA typing laboratories and population geneticists allowed finding useful solutions to the problem of estimating gene frequencies and testing basic population diversity statistics on highly complex HLA data (high numbers of alleles and ambiguities), with promising applications in either anthropological, epidemiological, or transplantation studies.

Mitochondrial DNA structure in North Africa reveals a genetic discontinuity in the Nile Valley

Human population movements in North Africa have been mostly restricted to an east-west direction due to the geographical barriers imposed by the Sahara Desert and the Mediterranean Sea. Although these barriers have not completely impeded human migrations, genetic studies have shown that an east-west genetic gradient exists. However, the lack of genetic information of certain geographical areas and the focus of some studies in parts of the North African landscape have limited the global view of the genetic pool of North African populations. To provide a global view of the North African genetic landscape and population structure, we have analyzed ∼2,300 North African mitochondrial DNA lineages (including 269 new sequences from Libya, in the first mtDNA study of the general Libyan population). Our results show a clinal distribution of certain haplogroups, some of them more frequent in Western (H, HV0, L1b, L3b, U6) or Eastern populations (L0a, R0a, N1b, I, J) that might be the result of human migrations from the Middle East, sub-Saharan Africa, and Europe. Despite this clinal pattern, a genetic discontinuity is found in the Libyan/Egyptian border, suggesting a differential gene flow in the Nile River Valley. Finally, frequency of the post-LGM subclades H1 and H3 is predominant in Libya within the H sequences, highlighting the magnitude of the LGM expansion in North Africa.

Genome-Wide and Paternal Diversity Reveal a Recent Origin of Human Populations in North Africa

The geostrategic location of North Africa as a crossroad between three continents and as a stepping-stone outside Africa has evoked anthropological and genetic interest in this region. Numerous studies have described the genetic landscape of the human population in North Africa employing paternal, maternal, and biparental molecular markers. However, information from these markers which have different inheritance patterns has been mostly assessed independently, resulting in an incomplete description of the region. In this study, we analyze uniparental and genome-wide markers examining similarities or contrasts in the results and consequently provide a comprehensive description of the evolutionary history of North Africa populations. Our results show that both males and females in North Africa underwent a similar admixture history with slight differences in the proportions of admixture components. Consequently, genome-wide diversity show similar patterns with admixture tests suggesting North Africans are a mixture of ancestral populations related to current Africans and Eurasians with more affinity towards the out-of-Africa populations than to sub-Saharan Africans. We estimate from the paternal lineages that most North Africans emerged ∼15,000 years ago during the last glacial warming and that population splits started after the desiccation of the Sahara. Although most North Africans share a common admixture history, the Tunisian Berbers show long periods of genetic isolation and appear to have diverged from surrounding populations without subsequent mixture. On the other hand, continuous gene flow from the Middle East made Egyptians genetically closer to Eurasians than to other North Africans. We show that genetic diversity of todays North Africans mostly captures patterns from migrations post Last Glacial Maximum and therefore may be insufficient to inform on the initial population of the region during the Middle Paleolithic period.

Ancient Local Evolution of African mtDNA Haplogroups in Tunisian Berber Populations

Abstract Our objective is to highlight the age of sub-Saharan gene flows in North Africa and particularly in Tunisia. Therefore we analyzed in a broad phylogeographic context sub-Saharan mtDNA haplogroups of Tunisian Berber populations considered representative of ancient settlement. More than 2,000 sequences were collected from the literature, and networks were constructed. The results show that the most ancient haplogroup is L3*, which would have been introduced to North Africa from eastern sub-Saharan populations around 20,000 years ago. Our results also point to a less ancient western sub-Saharan gene flow to Tunisia, including haplogroups L2a and L3b. This conclusion points to an ancient African gene flow to Tunisia before 20,000 BP. These findings parallel the more recent findings of both archaeology and linguistics on the prehistory of Africa. The present work suggests that sub-Saharan contributions to North Africa have experienced several complex population processes after the occupation of the region by anatomically modern humans. Our results reveal that Berber speakers have a foundational biogeographic root in Africa and that deep African lineages have continued to evolve in supra-Saharan Africa.

Recent Historical Migrations Have Shaped the Gene Pool of Arabs and Berbers in North Africa

North Africa is characterized by its diverse cultural and linguistic groups and its genetic heterogeneity. Genomic data has shown an amalgam of components mixed since pre-Holocean times. Though no differences have been found in uniparental and classical markers between Berbers and Arabs, the two main ethnic groups in the region, the scanty genomic data available have highlighted the singularity of Berbers. We characterize the genetic heterogeneity of North African groups, focusing on the putative differences of Berbers and Arabs, and estimate migration dates. We analyze genome-wide autosomal data in five Berber and six Arab groups, and compare them to Middle Easterns, sub-Saharans, and Europeans. Haplotype-based methods show a lack of correlation between geographical and genetic populations, and a high degree of genetic heterogeneity, without strong differences between Berbers and Arabs. Berbers enclose genetically diverse groups, from isolated endogamous groups with high autochthonous component frequencies, large homozygosity runs and low effective population sizes, to admixed groups with high frequencies of sub-Saharan and Middle Eastern components. Admixture time estimates show a complex pattern of recent historical migrations, with a peak around the 7th century C.E. coincident with the Arabization of the region; sub-Saharan migrations since the 1st century B.C. in agreement with Roman slave trade; and a strong migration in the 17th century C.E., coincident with a huge impact of the trans-Atlantic and trans-Saharan trade of sub-Saharan slaves in the Modern Era. The genetic complexity found should be taken into account when selecting reference groups in population genetics and biomedical studies.

Genetic Diversity in Tunisia: A Study Based on the GM Polymorphism of Human Immunoglobulins

The GM polymorphism of human immunoglobulins is analyzed in three Berber populations of southern Tunisia and compared to other GM data. Genetic diversity among Tunisian populations is higher than that among Europeans but does not exhibit any significant geographic or linguistic structure. This result suggests a complex pattern of genetic differentiation.

Allele frequencies for 15 autosomal STR markers in the Libyan population

Background: Until recently Libya remained the only state of the Maghreb without genetic evolution investigations of the genetic landscape of its population. Apart from some studies of Libyan Jews and Libyan Tuareg, only two recent investigations, based on autosomal ancestry informative SNP and mitochondrial DNA markers, have concerned the general Libyan population. Aim: The present work is the first to describe STR markers polymorphism in the general Libyan population in order to contribute to the analysis of its genetic diversity for forensic purposes. Subjects and Methods: Allele frequencies for 15 STR loci (CSF1PO, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D21S11, FGA, TH01, TPOX, VWA, D2S1338, D19S433) included in the AmpFlSTR Identifiler kit were determined in a sample of 99 unrelated individuals originating from the general Libyan population. Results: No deviations from Hardy–Weinberg equilibrium were observed, with the exception of CSF1PO. Genetic parameters of forensic interest such as combined power of discrimination (PD) and combined probability of exclusion (PE) showed values higher than 0.999. Comparisons with data from other North African populations showed significant differences between Libyans and Tunisians, Moroccans and Egyptians. Conclusions: The high informativity observed for these 15 STRs in a Libyan population demonstrates their usefulness for forensic and parental purposes.

Identification of the CCR5-Δ32 HIV resistance allele and new mutations of the CCR5 gene in different Tunisian populations

Polymorphisms in some chemokine receptor genes are associated with susceptibility to and progression of human immunodeficiency virus-1 (HIV-1) infection. Most mutations detected in the CC-chemokine receptor 5 (CCR5) gene are specific to different populations. In this study, we focused on polymorphisms of the CCR5 coding region in three healthy populations from Tunisia, corresponding to a cosmopolitan population from Tunis, and two isolated Berber populations. In addition to the CCR5-Delta32 deletion, eleven single nucleotide polymorphisms were detected. Some of these point mutations were associated with the same genotype and even the same haplotype. The (L55Q-C101X), I124, V131F, T143N, A159V, I237, T239A and G301R alleles have not been described previously, whereas the CCR5-Delta32, L55Q, A335V and Y339F variants have already been reported in the literature. The distribution and frequency of these variants were different among the three groups studied, a result in agreement with the mosaic genetic structure of the Tunisian population. To determine whether these alleles affect HIV-1 transmission, we compared allele frequencies between healthy and HIV-1 infected individuals from Tunis. The frequency of the CCR5-Delta32 variant was significantly different between the two groups, leading us to conclude that this mutation might confer protection against HIV infection in Tunisian populations.