Bio-demographic characteristics of children with Down syndrome, their siblings, and their parents in Moroccan population.

OBJECTIVE: In this study, we present the results of bio-demographic characteristics of households and associated factors with Down syndrome (DS) birth in Morocco. METHODS: We conducted a retrospective survey between 2014 and 2017 addressed to 277 families with 925 siblings and at least one child with DS (279 with DS). The data are collected using a standardized questionnaire in Marrakech-Safi region. Data were entered and analyzed using the statistical program SPSS statistics software for Windows (version 20.0). Chi-square (χ2) and student t tests were used for testing statistical significance. Differences were considered significant when the p-value <0.05. RESULTS: The binary logistic regression analysis between DS and non-DS children in their bio-demographic characteristics studied (sex, breastfeeding, duration of exclusive breastfeeding, birth weight, maternal age at birth, paternal age at birth, oral contraceptive use, duration of oral contraceptive use before pregnancy, child age and rank of birth) showed that only maternal age and paternal age at birth, duration of exclusive breastfeeding, birth weight and child age (OR= 1.08; 95%Cl: 1.04-1.13, OR= 1.04; 95%Cl: 1.00-1.08, OR= 0.95; 95%Cl: 0.92-0.98, OR= 0.31; 95%Cl: 0.22-0.44 and OR= 0.90; 95%Cl: 0.87-0.93, respectively). In the other hand, the comparison between some of socio and bio-demographic characteristics of households studied with data from National Population Survey and Family health (2018) showed a higher level of education in women and men in our sample. Similar results were shown in proportion of men and women in paid employment, the proportion of smoking and alcohol consumption among men and the rate of oral contraceptive use before pregnancy among women. CONCLUSION: Highlighting the bio-demographic characteristics of people with DS will help families to take good care of this group. .

Parents' perceptions of morbidities and some functional abilities in people with down syndrome in Morocco.

Objective: This study aimed to assess parental perceptions of morbidity and certain functional abilities in people with Down syndrome (DS) and their variability according to age and sex in Morocco. Material and Methods: A retrospective and analytical survey was conducted between May 2014 and November 2017, and addressed to the parents of 279 individuals with DS, including 161 boys (57.7%) aged 1-40 years. The sample was subdivised to tree age groups, children under 10 years old, adolescents aged 10-18 years and adults aged ≥ 18 years. Information about the identity of parents, age and sex of people with DS, their morbidity during the two years preceding the survey, and some functional abilities was collected. Data were entered and analyzed using the statistical program SPSS statistics software for Windows (version 20.0). Chi-square (χ2) test was used for testing statistical significance. Differences were considered significant when the p-value < 0.05. The multivariate analysis were used to identify the causes of morbidies independently associated with age and sex of child. Associations were measured in Odds ratio (OR) with 95% confidence intervals (95% Cl). Results: The most common factors of morbidity registered in the study sample with DS, included respiratory infections, visual disturbances, oral pathologies, and cardiac problems (75.4%, 72.1%, 59.3%, and 44.9%, respectively). The hearing deficit, cardiac problems, respiratory infections, and oral pathologies showed statistically significant differences among the three age groups. According to the participants parents' perceptions, half of them (50%) were able to walk at 30 months, talk at 72 months, sit at 16 months, crawl at 16 months and eat alone at 48 months old. Conclusion: People with DS at different ages present a set of potentially treatable diseases that require multidisciplinary medical monitoring. They also need early paramedical care to improve their functional abilities.

Allelic and haplotypic data of MHC class II Alu insertions in Ngazidja (Comoros archipelago) and insight on its historical biology.

This study aimed to analyse, for the first time, five MHC class II polymorphic Alu insertions in a population with a strong Sub-Saharan African genetic background: the Ngazidja islanders and compare its allelic and haplotypic data with Worldwide populations. The genotyping was performed in 80 individuals, using simple PCR and agarose gel electrophoresis methods. Allele and haplotype frequencies, genetic diversity, Hardy-Weinberg equilibrium deviations, normalized deviate of homozygotes and pairwise linkage disequilibrium were estimated. The phylogenetic analyses included the available population data. In Ngazidja, the MHC class II Alu insertion frequencies ranged from 0.119 for AluORF10 to 0.588 for AluDPB2. Concerning haplotypes, the most predominant were the ones with only the AluDPB2 insertion allele (AluDPB2*2-AluDQA2*1-AluDQA1*1-AluDRB1*1-AluORF10*1), followed by the theoretical ancestral haplotype with no Alu insertions (AluDPB2*1-AluDQA2*1-AluDQA1*1-AluDRB1*1-AluORF10*1) and finally the haplotype with the AluDPB2 and AluDQA1 Alu insertions (AluDPB2*2-AluDQA2*1-AluDQA1*2-AluDRB1*1-AluORF10*1) with frequencies of 19.2%, 15% and 12.9%, respectively. In the phylogenetic analyses, our results indicate that the Ngazidja people are genetically differentiated from the other populations of the analysis; we found also a new haplotype that can be probably characteristic of Sub-Saharans and finally confirm the usefulness of these markers as genetic and evolutionary tools for studying genetic variations among populations of different origins.

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.

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 Europe.

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.

The Arabian cradle: mitochondrial relicts of the first steps along the southern route out of Africa.

A major unanswered question regarding the dispersal of modern humans around the world concerns the geographical site of the first human steps outside of Africa. The "southern coastal route" model predicts that the early stages of the dispersal took place when people crossed the Red Sea to southern Arabia, but genetic evidence has hitherto been tenuous. We have addressed this question by analyzing the three minor west-Eurasian haplogroups, N1, N2, and X. These lineages branch directly from the first non-African founder node, the root of haplogroup N, and coalesce to the time of the first successful movement of modern humans out of Africa, ∼60 thousand years (ka) ago. We sequenced complete mtDNA genomes from 85 Southwest Asian samples carrying these haplogroups and compared them with a database of 300 European examples. The results show that these minor haplogroups have a relict distribution that suggests an ancient ancestry within the Arabian Peninsula, and they most likely spread from the Gulf Oasis region toward the Near East and Europe during the pluvial period 55-24 ka ago. This pattern suggests that Arabia was indeed the first staging post in the spread of modern humans around the world.

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 the 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 belonged 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 the E1b1b1b-M81 haplogroup among Moroccan Berber-speaking males with a decreasing gradient from south to north. The most prevalent subclade in this haplogroup was E1b1b1b2-M183, for which diffferences among these three groups were statistically significant between central and southern groups.

Internal diversification of mitochondrial haplogroup R0a reveals post-last glacial maximum demographic expansions in South Arabia.

Widespread interest in the first successful Out of Africa dispersal of modern humans ∼60-80 thousand years ago via a southern migration route has overshadowed the study of later periods of South Arabian prehistory. In this work, we show that the post-Last Glacial Maximum period of the past 20,000 years, during which climatic conditions were becoming more hospitable, has been a significant time in the formation of the extant genetic composition and population structure of this region. This conclusion is supported by the internal diversification displayed in the highly resolved phylogenetic tree of 89 whole mitochondrial genomes (71 being newly presented here) for haplogroup R0a-the most frequent and widespread haplogroup in Arabia. Additionally, two geographically specific clades (R0a1a1a and R0a2f1) have been identified in non-Arabic speaking peoples such as the Soqotri and Mahri living in the southern part of the Arabian Peninsula where a past refugium was identified by independent archaeological studies. Estimates of time to the most recent common ancestor of these lineages match the earliest archaeological evidence for seafaring activity in the peninsula in the sixth millennium BC.

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.

Polymorphisms influencing muscle phenotypes in North-African and Spanish populations.

AIM: The purpose of this study was to determine the allelic and genotypic frequency distribution of the C34T mutation in the muscle isoform of the adenosine monophosphate deaminase 1 (AMPD1) gene and of the missense substitution K153R in the myostatin (GDF8) gene in one Spanish and two North African populations. METHOD: One sample of 98 individuals was genotyped from the South of Spain (Alpujarra) and two samples from Morocco (77 Berbers and 78 Arabs). RESULTS: The frequency of the AMPD1 C34T mutation was lower in Berbers (0.071) compared with the Alpujarra cohort (0.153, p = 0.018). The GDF8 K153R substitution showed little variability among the three cohorts. CONCLUSIONS: Studies with larger cohorts and other ethnic groups are needed to corroborate that there does not exist any major variability in the genotype distribution of genes associated with muscle phenotypes in the South-Eastern Mediterranean area.

Population history of the Red Sea--genetic exchanges between the Arabian Peninsula and East Africa signaled in the mitochondrial DNA HV1 haplogroup.

Archaeological studies have revealed cultural connections between the two sides of the Red Sea dating to prehistory. The issue has still not been properly addressed, however, by archaeogenetics. We focus our attention here on the mitochondrial haplogroup HV1 that is present in both the Arabian Peninsula and East Africa. The internal variation of 38 complete mitochondrial DNA sequences (20 of them presented here for the first time) affiliated into this haplogroup testify to its emergence during the late glacial maximum, most probably in the Near East, with subsequent dispersion via population expansions when climatic conditions improved. Detailed phylogeography of HV1 sequences shows that more recent demographic upheavals likely contributed to their spread from West Arabia to East Africa, a finding concordant with archaeological records suggesting intensive maritime trade in the Red Sea from the sixth millennium BC onwards. Closer genetic exchanges are apparent between the Horn of Africa and Yemen, while Egyptian HV1 haplotypes seem to be more similar to the Near Eastern ones.

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.

COVID-19 pandemic: Effects of national lockdown on the state of health of patients with type 2 diabetes mellitus in a Moroccan population.

BACKGROUND: The complete lockdown caused by the COVID-19 pandemic had imposed a new behavior and lifestyle especially in terms of diet, physical activity, and the management of patients with chronic diseases. AIM: The present study aimed to analyze the impact of lockdown on the monitoring and care of type 2 diabetes mellitus (T2DM) patients in a Moroccan population from the Doukkala region. SUBJECTS AND METHODS: We conducted a retrospective observational study including 121 T2DM patients recruited from the Diabetes Diagnosis and Treatment Center of El Jadida city. Demographic, anthropometric, and biochemical data of our T2DM patients were recorded before and after lockdown that lasted 82 days. All patients have signed an informed consent after being informed about the purely scientific aims of the study. RESULTS: Our sample involved 84 women and 37 men with an age average of 57.31 ± 0.91 years. The effects of lockdown were more marked in women than in men: women showed a significant tendency to gain weight (from 78.13 ± 1.36 kg to 81.80 ± 1.45 kg; p-value < 0.000), that impacted the body mass index (p-value < 0.000); they also showed significant increases in HbA1c values (p-value = 0.001), significant decrease in systolic blood pressure (p-value = 0.0302) and a surprising increase in high-density lipoprotein cholesterol (p-value = 0.0132). The prevalence of metabolic syndrome in the women sample increased from 46.4% to 54.8% after the lockdown. In men, the negative effect of lockdown was observed only in HbA1c that values increased significantly from 8.66 ± 0.21% to 9.51 ± 0.25% (p-value = 0.0127). CONCLUSION: Our results reveal that lockdown had impacted negatively the health status of T2DM patients, especially women. We suggest an urgent development of programs aiming to improve the hygiene of life and to reduce the impact of future crises on patients suffering chronic diseases such as T2DM.

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

BACKGROUND: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

Population relationships in the Mediterranean revealed by autosomal genetic data (Alu and Alu/STR compound systems).

The variation of 18 Alu polymorphisms and 3 linked STRs was determined in 1,831 individuals from 15 Mediterranean populations to analyze the relationships between human groups in this geographical region and provide a complementary perspective to information from studies based on uniparental markers. Patterns of population diversity revealed by the two kinds of markers examined were different from one another, likely in relation to their different mutation rates. Therefore, while the Alu biallelic variation underlies general heterogeneity throughout the whole Mediterranean region, the combined use of Alu and STR points to a considerable genetic differentiation between the two Mediterranean shores, presumably strengthened by a considerable sub-Saharan African genetic contribution in North Africa (around 13% calculated from Alu markers). Gene flow analysis confirms the permeability of the Sahara to human passage along with the existence of trans-Mediterranean interchanges. Two specific Alu/STR combinations-CD4 110(-) and DM 107(-)-detected in all North African samples, the Iberian Peninsula, Greece, Turkey, and some Mediterranean islands suggest an ancient genetic background of current Mediterranean peoples.

Population genetics-informed meta-analysis in seven genes associated with risk to dengue fever disease.

Population genetics theory predicted that rare frequent markers would be the main contributors for heritability of complex diseases, but meta-analyses of genome-wide association studies are revealing otherwise common markers, present in all population groups, as the identified candidate genes. In this work, we applied a population-genetics informed meta-analysis to 10 markers located in seven genes said to be associated with dengue fever disease. Seven markers (in PLCE1, CD32, CD209, OAS1 and OAS3 genes) have high-frequency and the other three (in MICB and TNFA genes) have intermediate frequency. Most of these markers have high discriminatory power between population groups, but their frequencies follow the rules of genetic drift, and seem to have not been under strong selective pressure. There was a good agreement in directional consistency across trans-ethnic association signals, in East Asian and Latin American cohorts, with heterogeneity generated by randomness between studies and especially by low sample sizes. This led to confirm the following significant associations: with DF, odds ratio of 0.67 for TNFA-rs1800629-A; with DHF, 0.82 for CD32-rs1801274-G; with DSS, 0.55 for OAS3-rs2285933-G, 0.80 for PLCE1-rs2274223-G and 1.32 for MICB-rs3132468-C. The overall genetic risks confirmed sub-Saharan African populations and descendants as the best protected against the severer forms of the disease, while Southeast and Northeast Asians are the least protected ones. European and close neighbours are the best protected against dengue fever, while, again, Southeast and Northeast Asians are the least protected ones. These risk scores provide important predictive information for the largely naïve European and North American regions, as well as for Africa where misdiagnosis with other hemorrhagic diseases is of concern.

Cytochrome and sulfotransferase gene variation in north African populations.

AIM: To describe the diversity of four cytochrome and four sulfotransferase polymorphisms in six north African samples. Scarce data have been compiled for these samples despite the rich genetic background of north African populations. MATERIALS & METHODS: CYP3A4*1B, CYP3A4*17, CYP3A4*3, CYP3A5*3, SULT1A1*2, SULT1A2*2, SULT1A2*3 and SULT1E1*2 polymorphisms were explored in 556 individuals from Morocco, Algeria, Tunisia and Libya. RESULTS: Allele frequencies in our samples largely exceeded the variation ranges described for European populations, especially for CYP3A4*1B, SULT1A1*2 and SULT1A2*3. CONCLUSION: North African populations are heterogeneous, genetically diverse and show a considerable sub-Saharan African contribution for markers associated with increased risk of prostate cancer and with differential drug metabolism.

Genetic diversity of CYP3A4 and CYP3A5 polymorphisms in North African populations from Morocco and Tunisia.

The genes CYP3A4 and CYP3A5 form part of a cluster of cytochrome P450 genes involved in drug metabolism reactions. The allelic variants of these genes CYP3A4*1B, CYP3A4*3, CYP3A4*17 and CYP3A5*3 have been linked both to the reduced catalytic activity of cytochromes and to prostate cancer risk in whites, though scarce data exist for North African populations. The main objective of this study was to describe CYP3A4*3, CYP3A4*17, CYP3A4*1B and CYP3A5*3 allele frequencies and haplotype variation in Moroccan Berbers and the general Tunisian population. The data obtained for the Tunisian participants were consistent with the European allele frequency ranges described, while Moroccan Berbers showed high frequencies of CYP3A4*17 (1.8%), CYP3A4*3 (8.5%) and the CYP3A4*1B/CYP3A5*3 haplotype (18.4%). This haplotype, linked to an increased risk of prostate cancer, was detected at a much higher frequency compared with the present Tunisian population (8.4%) or with reported frequencies for populations such as whites (0.6%) or African Americans (5.3%).