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The strategic location of North Africa has led to cultural and demographic shifts, shaping its genetic structure. Historical migrations brought different genetic components that are evident in present-day North African genomes, along with autochthonous components. The Imazighen (plural of Amazigh) are believed to be the descendants of autochthonous North Africans and speak various Amazigh languages, which belong to the Afro-Asiatic language family. However, the arrival of different human groups, especially during the Arab conquest, caused cultural and linguistic changes in local populations, increasing their heterogeneity. We aim to characterize the genetic structure of the region, using the largest Amazigh dataset to date and other reference samples. Our findings indicate microgeographical genetic heterogeneity among Amazigh populations, modeled by various admixture waves and different effective population sizes. A first admixture wave is detected group-wide around the twelfth century, whereas a second wave appears in some Amazigh groups around the nineteenth century. These events involved populations with higher genetic ancestry from south of the Sahara compared to the current North Africans. A plausible explanation would be the historical trans-Saharan slave trade, which lasted from the Roman times to the nineteenth century. Furthermore, our investigation shows that assortative mating in North Africa has been rare., (© 2024. The Author(s).)

Hepatocellular carcinoma (HCC) is a multifactorial disease with both genetic and environmental factors contributing to its pathogenesis. ACYP2 is a gene that is related to cell differentiation, apoptosis and prevention of malignant tumors. The ACYP2 gene also affects telomere length. The aim of this study was to evaluate the association between ACYP2 single nucleotide polymorphisms (SNPs) (rs843711), and (rs843706) and incidence of HCC in Egyptian HCC patients. The study included 30 patients with HCC and 30 normal controls. Detection of ACYP2 gene SNPs rs843711, and rs843706 in all study participants was done using real time polymerase chain reaction (RT-PCR). The results showed that all participants including HCC patients and controls carried the heterozygous CA (100%) of the rs843706 SNP (p> 0.05). As for the rs843711, 3.3% of HCC patients had the homozygous TT genotype, 46.7% had the heterozygous CT genotype and 50% had the wild CC genotype, while in the control group, 60% had the heterozygous CT genotype and 40% had the wild CC genotype with no significant difference between both groups (p>0.05). We concluded that there was no association between SNPs ACYP2 rs843706 and rs843711 and occurrence of HCC., (Copyright© by the Egyptian Association of Immunologists.)

One of the most common neurological illnesses in the world is multiple sclerosis (MS), a chronic autoimmune demyelinating disease of the central nervous system (CNS). MS has both a genetic and an environmental origin. In terms of environmental factors, vitamin D deficiency is one of the most important risk factors and closely connected with gene polymorphisms involved in vitamin D metabolism, transport, or activity. Since vitamin D activity requires a receptor-mediated response, any changes to the vitamin D receptor (VDR) may have an effect on the pathophysiology of the disease. In this study, we aimed to identify the relationship between VDR gene polymorphisms, FokI A>G (rs2228570), ApaI A>C (rs7975232) and BsmI C>T (rs1544410) and MS. FokI, ApaI and BsmI genotypes were determined in 50 patients with relapsing remitting MS (RRMS) and in 50 control subjects. DNA was isolated from blood samples, and then FokI, ApaI and BsmI gene polymorphisms were identified using allelic discrimination real time polymerase chain reaction (PCR) assay. The distribution of FokI, ApaI and BsmI polymorphisms did not show any significant differences between MS patients and controls. Thus, we concluded that there is no association between the studied VDR gene polymorphisms and MS., (Copyright© by the Egyptian Association of Immunologists.)

Multiple sclerosis (MS) is a multifactorial polygenic disease; results from autoimmune and neurodegenerative processes which lead to multifocal lesions of the central nervous system. Axonal degeneration was found to be prominent in the inflammation period of MS and contribute to the progression of disability. Soluble N-ethylmaleimide sensitive factor attachment receptor (SNARE) complex plays a vital role in the release of neurotransmitter by synaptic vesicle fusion. Stx-1A protein (Stx-1A), a major component of the SNARE complex, is widely expressed in brain tissue. This study intended to evaluate the prevalence of the Stx-1A gene polymorphism (rs1569061) in the Egyptian population with MS and to investigate its association with various clinical factors. This study included 65 adult Egyptian MS patients and 35 age- and sex-matched normal control subjects. Diagnosis of MS was made by an experienced neurologist according to revised McDonald criteria. All Patients underwent full history taking, included Age of onset of MS, disease duration, disease course and degree of disability according to the Expanded Disability Status Scale (EDSS) and family history of neurological diseases. Stx-1A gene polymorphism (rs1569061) genotyping was performed by TaqMan assay based quantitative real time (qPCR) and verified by sanger sequencer. Genotype and allele frequencies of (rs1569061) did not differ significantly between case and control groups. No difference was detected when comparing the genotype frequency and the allele frequency to different disease parameters. Discrepancy of the minor allele frequency (MAF) of Stx-1A gene (rs1569061) between different populations was noted. In conclusion, our study in Stx-1A gene polymorphism (rs1569061) and MS showed that no difference between the patient and control as regards gene frequency and allele frequency. Predicting no association between the studied polymorphism and MS in the Egyptian population. However, discrepancy between different population was noted as regards the MAF for Stx-1A gene (rs1569061)., (Copyright© by the Egyptian Association of Immunologists.)

Breast cancer is the most malignant tumor among women in the world. Single nucleotide polymorphisms (SNPs) might better predict breast cancer prognosis. PvuII (T/C substitution), XbaI (A/G substitution), and aryl hydrocarbon (AhR) (G/A substitution) were evaluated as possible genetic prognostic factors for breast cancer. The aim of the current study was to assess the relation between PvuII (rs2234693), XbaI (rs9340799), and aryl hydrocarbon receptor gene polymorphisms AhR (rs2066853) in breast cancer prognosis. This was a case-control study that included 120 breast cancer patients classified into two groups. The first group included 60 patients with good prognostic factors, and the second group included 60 patients with poor prognostic factors. Blood samples were taken from all study participants to perform the genotyping assay. We found that positive genotypes of PvuII, XbaI, and AhR polymorphisms were strongly associated with better prognostic factors for breast cancer patients, while negative genotypes of PvuII and XbaI were more and significantly prevalent in poor prognostic breast cancer patients. We conclude that PvuII T/C, XbaI G/A, and AhR G/A alleles may be prognostic for breast cancer progression., (Copyright© by the Egyptian Association of Immunologists.)

This study aimed to identify BRCA1/2 mutational patterns in the tissue and blood of Egyptian colorectal cancer (CRC) patients and to study the possible correlation of this mutational pattern with Human papillomavirus (HPV) infection. Eighty-two colonoscopic biopsies and forty-six blood samples were collected from Egyptian CRC patients, as well as blood samples of age and sex-matched healthy controls (n = 43) were enrolled. The libraries were performed using Qiaseq Human BRCA1 and BRCA2 targeted DNA panel and sequenced via Ion proton sequencer. Also, the CRC tissues were subjected to conventional PCR targeting the HPV Late 1 (L1) region. Our analysis revealed that the BRCA-DNA damage pathway had been altered in more than 65% of the CRC patients. Comparing tissue and blood samples from CRC patients, 25 somatic mutations were found exclusively in tissue, while 41 germline mutations were found exclusively in blood. Additionally, we identified 23 shared BRCA1/2 pathogenic (PVs) mutations in both blood and tissue samples, with a significantly higher frequency in blood samples compared to tissue samples. The most affected exon in BRCA1 was exon 10, while the most affected exons in BRCA2 were 11, 14, 18, 24, and 27 exons. Notably, we revealed an ethnic-related cluster of polymorphism variants in our population closely related to South Asian and African ethnicities. Novel PVs were identified and submitted to the ClinVar database. HPV was found in 23.8% of the CRC tissues, and 54% of HPV-positive cases had somatic BRCA1/2 PVs. The results of this research point to a possible connection between infection with HPV and BRCA1/2 mutations in the occurrence of colorectal cancer in the Egyptian population, which has a mixed ethnic background. Our data also indicate that liquid biopsy (blood samples) may be more representative than tissue samples for detecting BRCA1/2 mutations. These findings may have implications for cancer screening and the development of personalized, targeted therapies, such as PARP inhibitors, which can effectively target BRCA1/2 mutations., (© 2023. The Author(s).)

Introduction: Mitochondria are maternally inherited cell organelles with their own genome, and perform various functions in eukaryotic cells such as energy production and cellular homeostasis. Due to their inheritance and manifold biological roles in health and disease, mitochondrial genetics serves a dual purpose of tracing the history as well as disease susceptibility of human populations across the globe. This work requires a comprehensive catalogue of commonly observed genetic variations in the mitochondrial DNAs for all regions throughout the world. So far, however, certain regions, such as North and East Africa have been understudied., Objectives: To address this shortcoming, we have created the most comprehensive quality-controlled North and East African mitochondrial data set to date and use it for characterizing mitochondrial genetic variation in this region., Methods: We compiled 11 published cohorts with novel data for mitochondrial genomes from 159 Sudanese individuals. We combined these 641 mitochondrial sequences with sequences from the 1000 Genomes (n = 2504) and the Human Genome Diversity Project (n = 828) and used the tool haplocheck for extensive quality control and detection of in-sample contamination, as well as Nanopore long read sequencing for haplogroup validation of 18 samples., Results: Using a subset of high-coverage mitochondrial sequences, we predict 15 potentially novel haplogroups in North and East African subjects and observe likely phylogenetic deviations from the established PhyloTree reference for haplogroups L0a1 and L2a1., Conclusion: Our findings demonstrate common hitherto unexplored variants in mitochondrial genomes of North and East Africa that lead to novel phylogenetic relationships between haplogroups present in these regions. These observations call for further in-depth population genetic studies in that region to enable the prospective use of mitochondrial genetic variation for precision medicine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Production and hosting by Elsevier B.V.)

Consanguineous marriages in Middle Eastern and North African (MENA) countries are deeply-rooted tradition and highly prevalent resulting into increased prevalence of autosomal recessive diseases including Inborn Errors of Immunity (IEIs). Molecular genetic testing is an important diagnostic tool for IEIs since it provides a definite diagnosis, genotype-phenotype correlation, and guide therapy. In this review, we will discuss the current state and challenges of genomic and variome studies in MENA region populations, as well as the importance of funding advanced genome projects. In addition, we will review the MENA underlying molecular genetic defects of over 2457 patients published with the common IEIs, where autosomal recessive mode of inheritance accounts for 76% of cases with increased prevalence of combined immunodeficiency diseases (50%). The efforts made in the last three decades in terms of international collaboration and of in situ capacity building in MENA region countries led to the discovery of more than 150 novel genes involved in IEIs. Expanding sequencing studies within the MENA will undoubtedly be a unique asset for the IEI genetics which can advance research, and support precise genomic diagnostics and therapeutics., Competing Interests: Competing interests The authors declared that they have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)