Mutaz Amin

Transmission of Plasmodium vivax in Duffy-negative individuals in central Sudan.

BACKGROUND Due to the recently observed rise in Plasmodium vivax incidence in Sudan and reported transmission in Duffy-negative individuals; we aimed to assess the possibility of P. vivax transmission in Duffy-negative individuals in Gezira state, central Sudan. METHOD A total of 126 suspected malaria patients were diagnosed with P. vivax infection using microscopy, RDT and PCR. PCR-RFLP was used to genotype participants Duffy status. RESULTS Forty eight (38%) were positive for P. vivax infection by PCR. Four patients (8.3%) were homozygous Duffy-negative. CONCLUSION These results confirm that P. vivax can infect Duffy-negative individuals, suggesting alternative mechanisms to bind and invade erythrocytes.

In Silico Analysis of SNPs in PARK2 and PINK1 Genes That Potentially Cause Autosomal Recessive Parkinson Disease

Introduction. Parkinsons disease (PD) is a common neurodegenerative disorder. Mutations in PINK1 are the second most common agents causing autosomal recessive, early onset PD. We aimed to identify the pathogenic SNPs in PARK2 and PINK1 using in silico prediction software and their effect on the structure, function, and regulation of the proteins. Materials and Methods. We carried out in silico prediction of structural effect of each SNP using different bioinformatics tools to predict substitution influence on protein structure and function. Result. Twenty-one SNPs in PARK2 gene were found to affect transcription factor binding activity. 185 SNPs were found to affect splicing. Ten SNPs were found to affect the miRNA binding site. Two SNPs rs55961220 and rs56092260 affected the structure, function, and stability of Parkin protein. In PINK1 gene only one SNP (rs7349186) was found to affect the structure, function, and stability of the PINK1 protein. Ten SNPs were found to affect the microRNA binding site. Conclusion. Better understanding of Parkinsons disease caused by mutations in PARK2 and PINK1 genes was achieved using in silico prediction. Further studies should be conducted with a special consideration of the ethnic diversity of the different populations.

MALARIA and BURKITT'S LYMPHOMA An IN SILICO ANALYSIS of GENE EXPRESSION LINKS BETWEEN MALARIA and BURKITT'S LYMPHOMA and POTENTIAL ANTICANCER ACTIVITY of ARTEMISININ DERIVATIVES

Background Burkitt’s lymphoma (BL) is an aggressive form of B-cell non-Hodgkin lymphoma. Endemic subtype of the disease showed a remarkable statistical and epidemiological association with malaria infection. Despite the numerous studies performed to explain this association; molecular mechanisms underlie such coincidence still remain unclear. Dissecting molecular mechanisms which link Malaria infection and Burkitt’s lymphoma can provide insights about reported anticancer action of certain antimalarial drugs, namely artemisinin derivatives. Methods Here we applied an integrative approach to investigate for potential links between malaria infection and endemic Burkitt’s lymphoma regarding their gene expression, and further explore common molecular mechanisms through which artemisinin compounds might act in endemic Burkitt’s lymphoma. Using gene expression data of malaria (Plasmodium falciparum infected erythroblasts) and endemic Burkitt’s lymphoma from Gene Expression Omnibus database, expression patterns in the two conditions were examined through clustering analysis using Self Organizing Maps, and then by significance testing of differentially expressed genes in each condition followed by Functional annotation using Gene Ontology clustering and Pathways analysis. Results Clustering analysis identified a significant overlap between the expression patterns in endemic Burkitt’s lymphoma and Plasmodium falciparum infected cells. Four out of the 12 identified clusters contained genes with similar expression patterns in both conditions. Differential expression analysis identified 1689 genes as significantly differentially expressed in endemic Burkitt’s lymphoma and 405 in malaria. Those genes were found to be related to important Gene Ontology terms and pathways. Interestingly 65% of the identified pathways in Malaria were overlapped with those identified in endemic Burkitt’s lymphoma. Several of these pathways reported to be related to actions of artemisinin derivatives. Conclusion Our In-silico analysis showed a significant molecular convergence between endemic Burkitt’s lymphoma and malaria. A number of 43pathways which demonstrated enrichment in tumour were shared with Plasmodium falciparum infected erythrocytes. Such pathways represent potential targets for antimalarial drugs to exert therapeutic effects in such malignancy.

Genetic Susceptibility to Asthma and Genetic Interactions in the 5q31-q33 and 16p11 Regions in Sudanese Families

Background: Asthma is a complex disorder with heterogeneous phenotypes attributed to the interactions of many genes and the environment. Numerous genetic studies have mapped asthma susceptibility genes to a region on chromosome 5q31-q33. This study aimed to determine the association of 10 candidate polymorphisms in IL-4, IL-5, IL-9, IL-13 and IL-4R genes in 5q31-q33 region with susceptibility to asthma in Sudanese families.Method: Fifty two multi cases families consisting of 141 known cases of asthma and 129 healthy individuals from Khartoum state were genotyped for seven SNPs on 5q31-33 region located in four candidate genes; IL4, IL5 IL13, IL9 and three SNPs in IL4Rα on chromosome 16p using multiplex PCR with Mass ARRAY system. Multiple logistic regression was used to test for association of asthma. P-value needed to achieve statistical significance taking multiple testing into account is P=0.005 (=0.05/10 (number of SNPs genotyped)). However, since SNPs within genes showed some degree of linkage disequilibrium and SNPs were selected as major SNPs for association with Asthma in other populations. Therefore, P £ 0.01 (=0.05/5 genes) can used as the P-value required to achieve correction for multiple testing.Result: Genotype and allelic frequencies of all SNPs were similar in both asthmatics and healthy subjects. Stepwise logistic regression demonstrated that SNP IL-13 rs2069743 was markedly associated with Asthma (P=0.008) and same SNP added significant main effects to IL-4 rs2070874 or IL-9 rs31563, whereas the reverse was not true, indicating that the main effect for association with asthma in this population is most strongly tagged by SNP IL-13 rs2069743.Conclusion: There is strong genetic association of SNPs in 5q31-q33 and 16p11 region and asthma.

Clinical and genetic characteristics of leukodystrophies in Africa

Recent understanding of the genetic basis of neurological disorders in Africa has grown rapidly in the last two decades. Africa harbors the largest genetic repertoire in the world which gives unique opportunity to discover novel variant, genes, and molecular pathways associated with various neurological diseases. Despite that, large-scale genomic and exome studies are severely lacking especially for neglected diseases such as leukodystrophies. This review aims to shed light on the currently developed research in leukodystrophies in Africa. We reviewed all research articles related to “Leukodystrophy in Africa” published in Medline/PubMed and Google Scholar databases up to date. We found very few studies in leukodystrophy from Africa, especially from the Sub-Saharan regions. Metachromatic leukodystrophy was the most studied type of leukodystrophy. Published studies from North Africa (Tunisia, Morocco, and Egypt) were very limited in either sample size (case studies or single/few family studies) or molecular methods (targeted sequencing or polymerase chain reaction-restriction fragment length polymorphisms). More studies (GWAS or large family studies) with advanced techniques such as exome or whole genome sequencing are needed to unveil the genetic basis of leukodystrophy in Africa. Unmasking novel genes and molecular pathways of leukodystrophies invariably lead to better detection and treatment for both Africans and worldwide populations.

Frequency of c.35delG Mutation in GJB2 Gene (Connexin 26) in Syrian Patients with Nonsyndromic Hearing Impairment

Background Hearing impairments (HI) are the most common birth defect worldwide. Very large numbers of genes have been identified but the most profound is GJB2. The clinical interest regarding this gene is very pronounced due to its high carrier frequency (0.5–5.4%) across different ethnic groups. This study aimed to determine the prevalence of common GJB2 mutations in Syrian patients with profound sensorineural HI. Methods We carried out PCR, restriction enzyme based screening, and sequencing of 132 Syrian patients diagnosed clinically with hereditary deafness for different GJB2 mutations. Results The result revealed that, in GJB2 gene, c.35delG is the most prevalent among affected studied subjects (13.64%), followed by c.457G>A (2.4%). Conclusion The benefit of this study on the one hand is its first report of prelingual deafness causative gene mutations identified by sequencing technology in the Syrian families. It is obvious from the results that the deployment in biomedical research is highly effective and has a great impact on the ability to uncover the cause of genetic variation in different genetic diseases.

A bioinformatic panel to interrogate thousands of ExAC variants with minor reference allele that are missed by conventional variant calling

In variation sites with minor reference alleles, overlooking the detection of homozygous reference genotypes results in inadequate identification of potential disease variants. Current variant calling practices miss these clinically relevant alleles warranting new approaches. More than 26,000 Eome Aggregation Consortium (ExAC) variants have a minor reference allele including 44 variants with known ClinVar disease alleles. We demonstrated how the current variant calling standards miss homozygous reference disease variants in these sites. We developed a bioinformatic panel that can be used to screen these variants using commonly available variant callers. We provide here a simple strategy to screen potential disease-causing variants when present in homozygous reference state.