Angiotensin Converting Enzyme 2 (ACE2) and COVID-19: An overview of its structure, physiologic role and its involvement in SARS-COV2 infection and therapy

Coronavirus disease of 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is of a great global and national public health concern. Structural studies suggested that the SARS-CoV2 binds through its spike-protein to target cells by interacting with the angiotensin-converting enzyme 2 (ACE2) receptor which is widely expressed in the heart, kidneys, lungs, gut and testes cells. This article reviews the structural and physiologic roles of the human ACE2 and its correlation with the SARS-CoV2 infection and therapy. Evidence has been provided that the amino acids 318-510 of the viral spike protein represent the receptor-binding domain (RBD) which binds to ACE2, especially by means of the critical amino acids at positions 479 and 487, then allowing virus tropism and propagation. ACE2 play a crucial role in the down regulation of the renin-angiotensin-aldosterone system (RAAS). The RAAS ACE-Angiotensin II-AT1R regulatory axis promotes detrimental effects on the host, such as vasoconstriction, generation of reactive oxygen species, inflammation and matrix remodeling. However, the ACE2-Ang 1-7-MasR axis counterbalances the activation of the classical RAS system which inhibits cell growth, inflammation and fibrosis. The ACE2 has a protective effect against organ damage, lung injury and underlying chronic diseases such as hypertension, diabetes, and cardiovascular diseases wich are linked with poor prognosis of healing in patients with COVID-19. On account of the protective effects of ACE2, the design and development of drugs enhancing its activity may become one of the most promising strategies for the therapy of COVID-19 in the future

Phylogeography of E1b1b1b-M81 Haplogroup and Analysis of its Subclades in Morocco

In this work, we have analyzed a total of 295 unrelated Berber-speaking men from the northern, center and southern of Morocco, in order to characterize frequency of E1b1b1b-M81 haplogroup and to refine the phylogeny of its subclades: E1b1b1b1-M107, E1b1b1b2-M183 and E1b1b1b2a-M165. For this purpose, we have typed four biallelic polymorphisms: M81, M107, M183 and M165. As results, a large majority of the Berber-speaking male lineages belong to the Y chromosomal E1b1b1b-M81 haplogroup. The frequency ranged from 79.1 to 98.5% in all localities sampled. Then, the E1b1b1b2-M183 was the most dominant subclade in our samples, which ranged from 65.1% to 83.1%. In contrast, the E1b1b1b1-M107 and E1b1b1b2a-M165 subclades weren’t found in our samples. Our results suggest a predominance of E1b1b1b-M81 haplogroup among Moroccan Berber-speaking male with a decreasing gradient from south to north. Then, the most prevalent subclade in this haplogroup was E1b1b1b2-M183 in which difference between these three groups was statistically significant between central and southern groups

The trans-Saharan slave trade - clues from interpolation analyses and high-resolution characterization of mitochondrial DNA lineages

<p>Abstract</p> <p>Background</p> <p>A proportion of 1/4 to 1/2 of North African female pool is made of typical sub-Saharan lineages, in higher frequencies as geographic proximity to sub-Saharan Africa increases. The Sahara was a strong geographical barrier against gene flow, at least since 5,000 years ago, when desertification affected a larger region, but the Arab trans-Saharan slave trade could have facilitate enormously this migration of lineages. Till now, the genetic consequences of these forced trans-Saharan movements of people have not been ascertained.</p> <p>Results</p> <p>The distribution of the main L haplogroups in North Africa clearly reflects the known trans-Saharan slave routes: West is dominated by L1b, L2b, L2c, L2d, L3b and L3d; the Center by L3e and some L3f and L3w; the East by L0a, L3h, L3i, L3x and, in common with the Center, L3f and L3w; while, L2a is almost everywhere. Ages for the haplogroups observed in both sides of the Saharan desert testify the recent origin (holocenic) of these haplogroups in sub-Saharan Africa, claiming a recent introduction in North Africa, further strengthened by the no detection of local expansions.</p> <p>Conclusions</p> <p>The interpolation analyses and complete sequencing of present mtDNA sub-Saharan lineages observed in North Africa support the genetic impact of recent trans-Saharan migrations, namely the slave trade initiated by the Arab conquest of North Africa in the seventh century. Sub-Saharan people did not leave traces in the North African maternal gene pool for the time of its settlement, some 40,000 years ago.</p

Molecular Variation in Endothelial Nitric Oxide Synthase Gene (eNOS) in Western Mediterranean Populations

Endothelial nitric oxide synthase (eNOS or NOS3) is the main responsible for nitric oxide (NO) production in vascular system and different polymorphisms have been identified in epidemiological studies. Trying to test the eNOS genetic variation in general populations we studied the 27-bp VNTR in intron 4 and G894T substitution in exon 7 markers in 6 Western Mediterranean populations (3 from Iberian Peninsula, 1 from North Africa, and 2 from Sardinia) and a sample from Ivory Coast. The VNTR frequencies in Western Mediterranean and Ivory Coast fit well into the ranges previously described for Europeans and Sub-Saharans respectively, and a typical African allele has been detected in polymorphic frequencies in the Berber sample. The G894T substitution presents the highest frequencies described for the T allele in the North Mediterranean populations. Linkage disequilibrium is present between both markers in all populations except in the Ivory Coast sample. The variation found for these polymorphisms indicates that they may be a useful tool for population studies even at microgeographical level

Reconciling evidence from ancient and contemporary genomes: a major source for the European Neolithic within Mediterranean Europe

Important gaps remain in our understanding of the spread of farming into Europe, due partly to apparent contradictions between studies of contemporary genetic variation and ancient DNA. It seems clear that farming was introduced into central, northern, and eastern Europe from the south by pioneer colonization. It is often argued that these dispersals originated in the Near East, where the potential source genetic pool resembles that of the early European farmers, but clear ancient DNA evidence from Mediterranean Europe is lacking, and there are suggestions that Mediterranean Europe may have resembled the Near East more than the rest of Europe in the Mesolithic. Here, we test this proposal by dating mitogenome founder lineages from the Near East in different regions of Europe. We find that whereas the lineages date mainly to the Neolithic in central Europe and Iberia, they largely date to the Late Glacial period in central/eastern Mediterranean Europe. This supports a scenario in which the genetic pool of Mediterranean Europe was partly a result of Late Glacial expansions from a Near Eastern refuge, and that this formed an important source pool for subsequent Neolithic expansions into the rest of Europ

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

ACKGROUND: 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

Phylogeography of E1b1b1b-M81 Haplogroup and Analysis of Its Subclades in Morocco

In this study we analyzed 295 unrelated Berber-speaking men from northern, central, and southern Morocco to characterize frequency of E1b1b1b-M81 haplogroup and to refine the phylogeny of its subclades: E1b1b1b1-M107, E1b1b1b2-M183 and E1b1b1b2a-M165. For this purpose, we typed four biallelic polymorphisms: M81, M107, M183, and M165. A large majority of the Berber-speaking male lineages belong to the Y-chromosomal E1b1b1b-M81 haplogroup. The frequency ranged from 79.1% to 98.5% in all localities sampled. E1b1b1b2-M183 was the most dominant subclade in our samples, ranging from 65.1% to 83.1%. In contrast, the E1b1b1b1-M107 and E1b1b1b2a-M165 subclades were not found in our samples. Our results suggest a predominance of E1b1b1b-M81 haplogroup among Moroccan Berber-speaking male with a decreasing gradient from south to north. The most prevalent subclade in this haplogroup was E1b1b1b2-M183, for which differences among these three groups were statistically significant between central and southern groups

Alu elements within the human major histocompatibility class I region in the Comoros Islands: genetic variation and population relationships

Background: Alu elements are attractive markers for population genetics, disease, forensics and paternity analyses, due to their particular characteristics. Five polymorphic Alu insertions within the MHC class I region have been little examined in human populations. Aim: The analysis of the genetic diversity of autochthonous Comorians from the three major islands of the archipelago by these polymorphic MHC Alus and to assess their relationships together and with other populations. Subjects and methods: Two hundred and fifty-seven unrelated participants from the Comoros archipelago, Grande Comore (86), Anjouan (93) and Moheli (78), were examined for five MHC Alu insertions. The data were analysed for intra- and inter-population genetic variation. Results: All MHC Alu were polymorphic in the three samples and only one significant differentiation was observed between Anjouan and Moheli. According to the MDS and AMOVA results, the populations included in the inter-population analyses were grouped in three major clusters according to their genetic ancestry. The haplotype diversity showed by the Comorians is higher than in previously studied African populations and occupies an intermediate position between African and Asian clusters. Conclusion: MHC Alu insertions are useful markers to study micro-geographical genetic variations. Using these polymorphisms, new insights have been obtained about the biological history and evolution of the Comoros

Genetic differences among North African Berber and Arab-speaking populations revealed by Y-STR diversity

Y-chromosome STR polymorphisms are inherited in a haploid state which makes them a powerful tool for easy tracing of paternal lineage and for use in human population evolutionary studies. North-African Y chromosomal diversity has traditionally been studied in order to find genetic and geographic associations as well as to test how natural and cultural barriers have affected the degree of genetic flow not only within North Africa but also in a wider Mediterranean context. The degree of Berber/Arab genetic differentiation in the Moroccan population has been tested for a complete set of forensic markers as sixteen Y-chromosomal short tandem repeats (STRs) (DYS19, DYS385, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 and GATA H4.1). The results suggest considerable population heterogeneity in North Africa.1.975 JCR (2011) Q2, 28/85 Biology, 61/158 Public, environmental & occupational healt

Usefulness of autosomal STR polymorphisms beyond forensic purposes: data on Arabic- and Berber-speaking populations from central Morocco

BACKGROUND: This work describes, for the first time, the profile of Middle Atlas Berbers and Arabic-speaking central Moroccans for 15 autosomal STR loci widely used in forensic sciences. AIM: The main objectives were to determine the degree of heterogeneity among different Moroccan samples to identify geographic or linguistic patterns and to evaluate the usefulness of forensic STRs in anthropological studies. SUBJECTS AND METHODS: Blood samples were collected from 71 Arabic-speakers and 75 Berbers from the regions of Doukkala (central-west coast) and Khenifra (Middle Atlas), respectively. The AmpFlSTR Identifier kit was used to genotype 15 autosomal STR in both samples. RESULTS: Middle Atlas Berbers showed slightly higher genetic variation values compared to Arabic-speakers, both in the number of alleles and heterozygosity. In order to assess population relationships, data from Morocco, Algeria, Tunisia, Libya, Egypt, Kuwait, Qatar, Palestine, Syria, South-Spain and Turkey were included in the analysis. Within Morocco, genetic distances followed a clear geographic pattern. In the Arabic-speaking sample the genetic proportion of 'Arabian' admixture was estimated in 13%. CONCLUSION: The low value of admixture suggests that the Arabization of Morocco had a reduced demographic impact, which should be taken with caution because it is based on autosomal STRs with low inter-population variation levels.1.484 JCR (2012) Q2 40/83 Biology; Q3, 86/158 Public, environmental & occupational healt