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BackgroundBurkitt’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.MethodsHere 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.ResultsClustering 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.ConclusionOur 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.

Background The conventional variant calling of pathogenic alleles in exome and genome sequencing requires the presence of the non-pathogenic alleles as genome references. This hinders the correct identification of variants with minor and/or pathogenic reference alleles warranting additional approaches for variant calling. Results More than 26,000 Exome Aggregation Consortium (ExAC) variants have a minor reference allele including variants with known ClinVar disease alleles. For instance, in a number of variants related to clotting disorders, the phenotype-associated allele is a human genome reference allele (rs6025, rs6003, rs1799983, and rs2227564 using the assembly hg19). We highlighted how the current variant calling standards miss homozygous reference disease variants in these sites and provided a bioinformatic panel that can be used to screen these variants using commonly available variant callers. We present exome sequencing results from an individual with venous thrombosis to emphasize how pathogenic alleles in clinically relevant variants escape variant calling while non-pathogenic alleles are detected. Conclusions This article highlights the importance of specialized variant calling strategies in clinical variants with minor reference alleles especially in the context of personal genomes and exomes. We provide here a simple strategy to screen potential disease-causing variants when present in homozygous reference state. Electronic supplementary material The online version of this article (10.1186/s12864-018-4433-3) contains supplementary material, which is available to authorized users.

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.

Vitamin C is a water-soluble compound with anti-oxidant properties that is essential for collagen synthesis and protection of living organisms against oxidative stress. These important roles, and the relatively large amounts of vitamin C required daily, likely explain why most vertebrate species are able to synthesize it but surprisingly; many species of anthropoid primates, guinea pigs, as well as some bats have lost the capacity to synthesize it. We hypothesized that the loss of vitamin C synthesis in early primate ancestors contributed to their relatively long life spans through up-regulation of hypoxia induced factor 1α (HIF1α), a transcription factor that plays an essential role in cellular response to oxidative stress.

A group of SNPs in 5q31, genotyped from Hausa tribe of Koka village in eastern Sudan; an area endemic with malaria and visceral leishmaniasis, were analyzed by The Leishmaniasis research group and found to have significant excess of heterozygosis level and departure from HWE and assumed to be due to natural selection resulting from notorious deadly outbreaks since various ethnic groups from western Sudan settled the area although sequence information in the 5q31 region did not detect functional SNPs that could be associated with such drastic phenotypes. Malaria was thought to inflict inferior selective pressure due to the mild clinical phenotype observed. Taking advantage of follow up phenotype data sets available from the Malaria Gen study we re-analyzed these genotypes using different bioinformatics software to determine their effect on the regulation, function and expression of interleukins, miRNA binding and splicing mechanism. The SNPs were found to potentially affect the binding of many transcription factors that regulate the expression of IL-4 and IL-13 and stability of IL-5 mRNA. Association of haplotypes susceptibility revealed that the haplotype of low cytokine TH2 profile is associated with higher risk of malaria infection (P-value = 0.02). Through modulating TH2 cytokine response; the excess heterozygosity in 5q31 is explained with the phenomenon of overdominance between malaria and visceral leishmaniasis, acted by natural selection and driving the locus towards optimum response.

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.

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.

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.

Plasmodium falciparumis a predominant malaria species that infects humans in the African continent. A recent WHO report estimated 95% and 5% ofP. falciparumandP. vivaxmalaria cases, respectively, in Sudan. However many laboratory reports from different areas in Sudan indicated otherwise. In order to verify, we selected four hundred suspected malaria cases from Aljabalain area located in the White Nile state, central Sudan, and diagnosed them with quality insured microscopy and species-specific nested PCR. Our results indicated that the proportion ofP. vivaxinfections among suspected malaria cases was high. We found that on average 20% and 36.5% of malaria infections in both study areas were caused byP. vivaxusing both microscopy and PCR, respectively. This change in pattern is likely due to the recent demographic changes and high rate of immigration from neighbouring countries in the recent years. This is the first extensive clinical study of its kind that shows rising trend inP. vivaxmalaria cases in White Nile area, Sudan.

Introduction. Parkinson’s 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 Parkinson’s 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.

Background: Malaria is a major health problem, with over one third of worldwide populations currently at risk. Determining the genetic diversity of plasmodium parasites is essential for assessing the efficacy of antimalarial drugs and for future vaccine development. This study investigated the genetic diversity of P. falciparum merozoite surface protein 2 (MSP2), and multiplicity of infection (MOI) in different geographic regions in Sudan. Methods: A total of 271 patients with uncomplicated malaria were recruited from four ecological sites during malaria transmission season, 2011-2013. P. falciparum was confirmed using species specific primers targeting the rDNA gene. All P. falciparum positive samples were genotyped for the major MSP2 allelic families (IC1/3D7 and FC27 MSP2 allele) using nested PCR. Multiplicity of infection and allele frequencies were determined. Results: A total of 241 samples (88.9%) were confirmed positive for P. falciparum. The number of different MSP2 alleles were 14, 15, 13 and 12 in Khartoum, Gezira, River Nile and Red Sea states, respectively. The 3D7 allelic family was more prevalent in the states of Khartoum, Gezira, River Nile and Red Sea compared to the FC27 allelic family. Multiclonal infections were observed in 25.8% of patients, with a mean multiplicity of infection (MOI) of 1.45. MOIs were highest in the age group over 40, with an average of 2 and 1.68 in Khartoum and Gezira states, respectively, however MOIs in River Nile and Red Sea states were higher in age groups below 18, with an average of 1.37 and 1.33, respectively. Conclusions: MSP2 allelic genotyping revealed MOI and diversity of the Sudanese P. falciparum isolates. The results of our study are expected to influence current and future malaria control strategies, since the MOI predicts development of clinical malaria and subsequent efficacy of antimalarial treatment.

Background Multiplicity and genetic diversity of Plasmodium falciparum infection might play a role in determining the clinical outcome of malaria infection and could be a fair reflection of the disease transmission rate. This study investigated the genetic diversity of P. falciparum and multiplicity of infection in relation to the severity of malaria and age of patients in Gezira State, Sudan. Methods A cross-sectional health facilities-based survey was conducted in Gezira State, Sudan in January 2012. A total of 140 P. falciparum malaria patients diagnosed with microscopy and confirmed using nested PCR were recruited and classified into uncomplicated malaria and severe malaria states according to the standard WHO criteria. DNA was extracted and MSP1 and MSP2 allelic families were determined using nested PCR. Results The overall multiplicity of infection (MOI) was 2.25 and 2.30 and 2.15 for uncomplicated and severe malaria respectively. There were no statistically significant differences between uncomplicated and severe malaria (SM) patient groups in MOI with regard to MSP1, MSP2 and overall MOI (Mann-Whitney U-test; all P