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

Comparison of SARS-cov-2 RdRp protein with SARS-cov RdRp protein

The World Health Organization (WHO) declared, on January 30, 2020, a public health emergency of international scope because of the emergence of a new virus called SARS-cov-2. This new virus belongs to the coronavirus family and has a protein called RNA-dependent RNA polymerase (RdRp) which is responsible for the replication of viral RNA. RdRp protein is one of the most primary targets for antiviral drug discoveries. The aim of this paper was to compare the amino acid sequence of the RdRp of SARS-cov-2 with that of SARS-cov. Thus, we found that there is a 96% sequence similarity between them. Indeed, there is only a difference at the level of 32 amino acids. Interestingly, only one residue at C Motif and two residues at D Motif are different. However, all the residues of the motifs A, B, E, F and G are 100% identical with those of SARS-cov-RdRp

How is the SARS-cov-2 virus transmitted ?

Since December 2019, the recent outbreak of coronavirus disease (COVID-19) has continued to spread drastically around the world. To date, no approved drug or vaccine is available to treat or prevent this new coronavirus (SARS-CoV-2) infection.Unprecedented global effort has been made by researchers to understand the various routes of SARS-CoV-2 virus transmission in order to effectively preventthe contamination. In this review, we discuss the updated literature regarding the different modes of SARS-CoV-2 transmission

Cytogenetic analysis and SRY gene detection in four moroccan brothers with Disorder of sex development

The objective of this study is to determine the genetic cause of the disorder of sex development on Moroccan family. Indeed, the genomics and human genetics laboratory at the Pasteur Institute of Morocco recruited four brothers with ambiguous genitalia. Cytogenetic analysis of the first brother revealed the presence of a chimeric karyotype 46, XX/46, XY with the presence of the SRY gene. The other three brothers present a normal female karyotype 46, XX with the presence of the SRY gene

Y chromosome microdeletions in infertile Moroccan males: 10 years laboratory experience in AZF deletions

Genetic causes of male infertility are abnormalities in chromosome numbers and/or structures, Y-chromosome deletions and gene mutations. Genetic screening of male infertility is rarely done in our country. The purpose of the study was to investigate the frequencies and types of Y chromosome microdeletions in infertile men, based on studies done in the Human Genetics Laboratory of the Pasteur Institute in Morocco.A total of 543 infertile men were screened for Y chromosome microdeletions.The prevalence of AZF Y-chromosome microdeletions among infertile men range from 3% to 10% depending on patients selected. The most frequent microdeletions were detected in the AZFc region, followed by AZFbc, AZFb, AZFa, AZFab.These results indicate the need for Y chromosome microdeletion screening for better management of infertile patients.We hope to encourage use of genetic diagnosis and also research in this field to initiate collaboration for clinical management and appropriate genetic diagnosis and counselling for male infertility

A new least squares method for estimation and prediction based on the cumulative Hazard function

In this paper, the cumulative hazard function is used to solve estimation and prediction problems for generalized ordered statistics (defined in a general setup) based on any continuous distribution. The suggested method makes use of Rényi representation. The method can be used with type Ⅱ right-censored data as well as complete data. Extensive simulation experiments are implemented to assess the efficiency of the proposed procedures. Some comparisons with the maximum likelihood (ML) and ordinary weighted least squares (WLS) methods are performed. The comparisons are based on both the root mean squared error (RMSE) and Pitman's measure of closeness (PMC). Finally, two real data sets are considered to investigate the applicability of the presented methods

Genetic study of sex inversion in humans

Sex reversal is considered to be a form of disorders of sex development or DSD (disorders/Differences of sex development). This is an inconsistency between gonadal, phenotypic and chromosomal sex. Sexual development, including the development of gonads and organs reproduction and the acquisition of secondary sexual characteristics, is under genetic control. Indeed, following the bibliographic study carried out in this report, we were able to better understand the pathophysiology of sex reversal, enumerate the associated genetic mutations and identify the signaling pathways affected. In addition, a retrospective study was performed to determine the frequency of sex reversal compared to other categories of DSD. This work focused on a sample of 981 patients with clinical signs indicating the presence of DSD. These patients presented to the Cytogenetics laboratory of the Institut Pasteur in Morocco between the years 2011 and 2021. The karyotype was performed on a heparinized tube according to the standard method. Based on the karyotype results, we found 74 cases of sex inversion corresponding to 7.54%. Abnormal karyotypes accounted for 37.31% with a predominance of Turner syndrome (41.53%), 26.23% of Klinefelter syndrome, 12.3% of patients presented with XY female type sex inversion, 7.92% with sex reversal type XX men and 7.65% had mixed gonadal dysgenesis. Finally, to guide the diagnosis, we established a course of action indicating the genes which are the most incriminated in the two types of sex inversion

Mutational analysis of the RB1 gene in Moroccan patients with retinoblastoma

PURPOSE: Retinoblastoma (RB), the most common intraocular tumor occurring in infancy and early childhood, is most often related to mutations in the RB1 gene. In this study, we screened the RB1 germline mutations in 41 unrelated Moroccan patients with retinoblastoma, 25 heritable cases, and 16 sporadic unilateral cases. METHODS: After complete ophthalmic examinations were performed and consent obtained, DNA was extracted from peripheral blood, and screening of RB1 mutations was performed with PCR direct sequencing of the promoter and the 27 coding exons of the RB1 gene. RESULTS: We identified ten germline mutations in 10/41 (24.39%) unrelated patients, among which three had not been previously reported. The mutation detection rate was 40% (10/25) in the heritable cases and 0% (0/16) in the sporadic unilateral cases. Of these mutations, six were nonsense, and three were frameshifts, all associated with severe phenotypes resulting in bilateral and multifocal tumors. One splice site mutation was found in a familial case associated with a low expressivity phenotype resulting in unilateral and unifocal tumors. Moreover, eight intronic variants were identified, three of which were novel. CONCLUSIONS: This first report of RB1 gene screening in Moroccan patients with retinoblastoma shows a comparable mutational spectrum to those reported previously, which has evident importance for managing patients with retinoblastoma and their families

Dominant ACO2 mutations are a frequent cause of isolated optic atrophy.

Biallelic mutations in ACO2, encoding the mitochondrial aconitase 2, have been identified in individuals with neurodegenerative syndromes, including infantile cerebellar retinal degeneration and recessive optic neuropathies (locus OPA9). By screening European cohorts of individuals with genetically unsolved inherited optic neuropathies, we identified 61 cases harbouring variants in ACO2, among whom 50 carried dominant mutations, emphasizing for the first time the important contribution of ACO2 monoallelic pathogenic variants to dominant optic atrophy. Analysis of the ophthalmological and clinical data revealed that recessive cases are affected more severely than dominant cases, while not significantly earlier. In addition, 27% of the recessive cases and 11% of the dominant cases manifested with extraocular features in addition to optic atrophy. In silico analyses of ACO2 variants predicted their deleterious impacts on ACO2 biophysical properties. Skin derived fibroblasts from patients harbouring dominant and recessive ACO2 mutations revealed a reduction of ACO2 abundance and enzymatic activity, and the impairment of the mitochondrial respiration using citrate and pyruvate as substrates, while the addition of other Krebs cycle intermediates restored a normal respiration, suggesting a possible short-cut adaptation of the tricarboxylic citric acid cycle. Analysis of the mitochondrial genome abundance disclosed a significant reduction of the mitochondrial DNA amount in all ACO2 fibroblasts. Overall, our data position ACO2 as the third most frequently mutated gene in autosomal inherited optic neuropathies, after OPA1 and WFS1, and emphasize the crucial involvement of the first steps of the Krebs cycle in the maintenance and survival of retinal ganglion cells