Human Alu insertion polymorphisms in North African populations

Several features make Alu insertions a powerful tool used in population genetic studies: the polymorphic nature of many Alu insertions, the stability of an Alu insertion event and, furthermore, the ancestral state of an Alu insertion is known to be the absence of the Alu element at a particular locus and the presence of an Alu insertion at the site that forward mutational change. This study analyses seven Alu insertion polymorphisms in a sample of 297 individuals from the autochthonous population of Tunisia (Thala, Smar, Zarzis and Bou Salem) and Libya with the aim of studying their genetic structure with respect to the populations of North Africa, Western, Eastern and Central Europe. The comparative analyses carried out using the MDS and AMOVA methods reveal the existence of spatial heterogeneity, and identify four population groups. Study populations (Libya, Smar, Zarzis and Bou Salem) are closest to North African populations whereas Thala is isolated and is closest to Western European populations. In conclusion, Results of the present study support the important role that migratory movements have played in the North African gene pool, at least since the Neolithic period

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 today's 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.This study was supported in parts by Spanish Government MCINN grant CGL2010-14944/BOS and Programa de Cooperación Interuniversitaria e Investigación Científica, Spanish Ministry of Foreign Affairs and Cooperation grants A75180/06, A/8394/07, B/018514/08, A1/040218/11.Peer Reviewe

A Distinctive Pattern of Diversity for the TAS2R38 Gene in North Africa

The TAS2R38 gene is involved in bitter taste perception. This study documents the distinctive diversity patterns in Northern Africa of functional SNPs rs713598 and rs1726866 at the TAS2R38 locus and places those patterns in the context of global TAS2R38 diversity. We analyzed data previously genotyped with Taqman Applied Biosystem for rs713598 and rs1726866 for 375 unrelated subjects (305 Tunisians from seven locations: Mahdia, Sousse, Kesra, Nebeur, Kairouan, Smar and Kerkennah plus 70 Libyans). Data were analyzed to present haplotypes and genotypes and were compared to the data from worldwide populations. We provide information about TAS2R38 diversity in a part of the world that is relatively under-studied. Considering respectively the two SNPs rs713598 and rs1726866, the (C-A) nucleotide haplotype leading to PV amino acid haplotype is extremely rare almost everywhere, but it is relatively frequent (between 6% and 10%) in Northern Africa where it does coexist with the globally common haplotypes (PA, AA and AV). Given its higher frequency in Northern Africa, we propose the (C-A) haplotype as a biogeographic marker for forensic purposes

The effect of tobacco, XPC, ERCC2 and ERCC5 genetic variants in bladder cancer development

<p>Abstract</p> <p>Background</p> <p>In this work, we have conducted a case-control study in order to assess the effect of tobacco and three genetic polymorphisms in <it>XPC, ERCC2 and ERCC5 </it>genes (rs2228001, rs13181 and rs17655) in bladder cancer development in Tunisia. We have also tried to evaluate whether these variants affect the bladder tumor stage and grade.</p> <p>Methods</p> <p>The patients group was constituted of 193 newly diagnosed cases of bladder tumors. The controls group was constituted of non-related healthy subjects. The rs2228001, rs13181 and rs17655 polymorphisms were genotyped using a polymerase chain reaction-restriction fragment length polymorphism technique.</p> <p>Results</p> <p>Our data have reported that non smoker and light smoker patients (1-19PY) are protected against bladder cancer development. Moreover, light smokers have less risk for developing advanced tumors stage. When we investigated the effect of genetic polymorphisms in bladder cancer development we have found that ERCC2 and ERCC5 variants were not implicated in the bladder cancer occurrence. However, the mutated homozygous genotype for XPC gene was associated with 2.09-fold increased risk of developing bladder cancer compared to the control carrying the wild genotype (p = 0.03, OR = 2.09, CI 95% 1.09-3.99). Finally, we have found that the XPC, ERCC2 and ERCC5 variants don't affect the tumors stage and grade.</p> <p>Conclusion</p> <p>These results suggest that the mutated homozygous genotype for XPC gene was associated with increased risk of developing bladder. However we have found no association between rs2228001, rs13181 and rs17655 polymorphisms and tumors stage and grade.</p

Etude de l Implication de la voie de signalisation Notch, dans les modifications phénotypiques et histopathologiques du cartilage articulaire, au cours de l arthrose

Notch joue un rôle important dans les phénomènes de différenciation, prolifération et apoptose des cellules. Vu l implication de ces processus dans la pathogénie de l arthrose, nous sommes intéressés à étudier le rôle de Notch dans cette pathologie.D une part, nous avons étudié le profil d expression Notch, dans le cartilage du genou sain versus arthrosique. Nous montrons, par immunohistochimie que la voie Notch est activée, au cours de l arthrose. D autre part, nous avons analysé le rôle de la cascade Notch dans la dédifférenciation des chondrocytes articulaires murins, induite, par passages successifs, in vitro. Nous révélons qu elle serait impliquée dans la dégradation du collagène II, probablement à travers une régulation positive de l expression de MMP13.Ce travail permet de mieux comprendre les mécanismes à l origine de l activation Notch au cours de l arthrose.PARIS-BIUP (751062107) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceTunisiaFRT

Ancient Local Evolution of African mtDNA Haplogroups in Tunisian Berber Populations

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. Pay-Per-View Download To access this article as a PDF pay-per-view download via BioOne, please click here

OntoContext, a new python package for gene contextualization based on the annotation of biomedical texts

Motivation : The automatic mining for bibliography exploitation in given contexts is a challenge according to the increasing number of scientific publications and new concepts. Several indexing systems were developed for biomedical literature. However, such systems have failed to produce contextualised research of genes and proteins and automatically group texts according to shared concepts. In this paper, we present OntoContext, a contextualization system crossing the use of biomedical ontologies to annotate texts containing terms related to cell populations, anatomical locations and diseases and to extract gene, RNA or protein names in these contexts. Results : OntoContext, a new python package contains two modules. The “annot” module for “annotation” function, is based on combination of morphosyntactic labelling and exact matching and on dictionaries derived from the Cell Ontology, the UBERON Ontology (anatomical context), the Human Disease Ontology and geniatagger, (which contains particular tags for gene-related names). The “annot” output is used as input for the second module “crisscross” generating lists of gene-related names obtained by crossing annotations from the three mentioned ontologies. OntoContext showed better performances than NCBO Annotator after evaluation on two text corpuses. OntoContext is freely available in the pypi

Targeting Tumor Metabolism: A New Challenge to Improve Immunotherapy

Currently, a marked number of clinical trials on cancer treatment have revealed the success of immunomodulatory therapies based on immune checkpoint inhibitors that activate tumor-specific T cells. However, the therapeutic efficacy of cancer immunotherapies is only restricted to a small fraction of patients. A deeper understanding of key mechanisms generating an immunosuppressive tumor microenvironment (TME) remains a major challenge for more effective antitumor immunity. There is a growing evidence that the TME supports inappropriate metabolic reprogramming that dampens T cell function, and therefore impacts the antitumor immune response and tumor progression. Notably, the immunosuppressive TME is characterized by a lack of crucial carbon sources critical for T cell function and increased inhibitory signals. Here, we summarize the basics of intrinsic and extrinsic metabolic remodeling and metabolic checkpoints underlying the competition between cancer and infiltrating immune cells for nutrients and metabolites. Intriguingly, the upregulation of tumor programmed death-L1 and cytotoxic T lymphocyte-associated antigen 4 alters the metabolic programme of T cells and drives their exhaustion. In this context, targeting both tumor and T cell metabolism can beneficially enhance or temper immunity in an inhospitable microenvironment and markedly improve the success of immunotherapies

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

Versión final disponible en www3.interscience.wiley.comHuman 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.Peer reviewe