Hiba Mohamed - Academia.edu (original) (raw)

Papers by Hiba Mohamed

Research paper thumbnail of The Time of Young Scientists Response

Research paper thumbnail of Estrogen Receptor 1 Gene (ESR1) rs2234693 Polymorphism and Breast Cancer Risk in Saudi Women

Asian Pacific Journal of Cancer Prevention, 2020

Breast cancer (BC) is a serious health issue, causing changes within the body cells and out of co... more Breast cancer (BC) is a serious health issue, causing changes within the body cells and out of control cell grow (

Research paper thumbnail of Fibroblast growth factor receptor 2 gene (FGFR2) rs2981582T/C polymorphism and susceptibility to breast cancer in Saudi women

Saudi Journal of Biological Sciences, 2021

Fibroblast growth factor receptor 2 is a protein encoded by FGFR2 gene and plays an important rol... more Fibroblast growth factor receptor 2 is a protein encoded by FGFR2 gene and plays an important role in cellular growth. This study was conducted to investigate a potential association of FGFR2 rs2981582 with breast cancer. DNA was obtained from 137 Formalin-fixed, paraffin-embedded tumors and 98 normal breast tissue samples. Genotypes were carried out with PCR-RFLP. The odds ratio and 95% confidence interval (CI) were used to evaluate the power of the associations. A significant association between FGFR2 rs2981582 C allele and susceptibility to breast cancer was found (p-value < 0.0001, Odds Ratio = 2.3, %95 CI (1.5–3.0). No significant differences in FGFR2 rs2981582 genotypes and alleles distribution among breast patients with different hormonal receptor status (p > 0.05) were detected. However, a significant difference was found in genotypes and alleles distribution in ER+, PR- and HER2 between breast cancer cases and controls. This study showed an association of FGFR2 rs2981...

Research paper thumbnail of Allele Frequency and Genotype Distribution of 9 SNPs in the Kazakh Population

Journal of Pharmacogenomics & Pharmacoproteomics, 2014

The CYP2C9 gene has high genetic polymorphism. The structural gene polymorphisms CYP2C9-R144C (CY... more The CYP2C9 gene has high genetic polymorphism. The structural gene polymorphisms CYP2C9-R144C (CYP2C9*2) and I359L (CYP2C9*3) are the most well-studied. The allele CYP2C9*2 reduces the warfarin dose by 40% for heterozygotes and 68% by homozygotes, and the CYP2C9*3 allele by 40 and 85%, respectively. This polymorphic variant explained 14.5% of the interindividual variability in the dose of warfarin together with non-genetic predictors, such as age, body weight and height [2]. VKORC1 gene The VKORC1 gene on chromosome 16 is one of the major genes associated with effective doses of coumarin anticoagulants. Many mutations are associated with a deficiency in this enzyme. The allelic variant VKORC1 c.-1639G>A determines up to 30% of the variability in warfarin dosage [3-8].

Research paper thumbnail of Interleukin 10 Gene Polymorphisms and Development of Post Kala-Azar Dermal Leishmaniasis in a Selected Sudanese Population

Public Health Genomics, 2009

Background: Post kala-azar dermal leishmaniasis (PKDL) is a cutaneous form of disease that develo... more Background: Post kala-azar dermal leishmaniasis (PKDL) is a cutaneous form of disease that develops at variable times after individuals have received treatment for clinical visceral leishmaniasis (VL). The study aimed to investigate the possible role of interleukin 10 (IL-10) and development of PKDL. Methods: 77 families composed of 41 complete case-parent trios and 36 case-parent pairs from the Masalit ethnic group were genotyped for 3 IL10 promoter polymorphisms: -1082A/G, -819C/T and -592C/A. Results: Single point analysis using the transmission disequilibrium test showed no evidence of association between any of these IL10 promoter single nucleotide polymorphisms (SNPs) and development of PKDL. Haplotype analysis performed using TRANSMIT showed borderline significance between PKDL and the haplotype AA across -592C/A and -1082A/G (p = 0.053). Haplotypes GCC (0.33) and ATA (0.30) were the common haplotypes in this Sudanese population. Allele frequencies for the 3 SNPs differed sig...

Research paper thumbnail of Y Chromosome Lineage- and Village-Specific Genes on Chromosomes 1p22 and 6q27 Control Visceral Leishmaniasis in Sudan

PLoS Genetics, 2007

Familial clustering and ethnic differences suggest that visceral leishmaniasis caused by Leishman... more Familial clustering and ethnic differences suggest that visceral leishmaniasis caused by Leishmania donovani is under genetic control. A recent genome scan provided evidence for a major susceptibility gene on Chromosome 22q12 in the Aringa ethnic group in Sudan. We now report a genome-wide scan using 69 families with 173 affected relatives from two villages occupied by the related Masalit ethnic group. A primary ten-centimorgan scan followed by refined mapping provided evidence for major loci at 1p22 (LOD score 5.65; nominal p ¼ 1.72 3 10 À7 ; empirical p , 1 3 10 À5 ; k S ¼ 5.1) and 6q27 (LOD score 3.74; nominal p ¼ 1.68 3 10 À5 ; empirical p , 1 3 10 À4 ; k S ¼ 2.3) that were Y chromosomelineage and village-specific. Neither village supported a visceral leishmaniasis susceptibility gene on 22q12. The results suggest strong lineage-specific genes due to founder effect and consanguinity in these recently immigrant populations. These chance events in ethnically uniform African populations provide a powerful resource in the search for genes and mechanisms that regulate this complex disease.

Research paper thumbnail of SLC11A1 (formerly NRAMP1) and susceptibility to visceral leishmaniasis in The Sudan

European Journal of Human Genetics, 2003

Genetic susceptibility to visceral leishmaniasis (VL) is indicated by differences in incidence an... more Genetic susceptibility to visceral leishmaniasis (VL) is indicated by differences in incidence and clinical phenotypes between ethnic groups in Sudan. In mice, innate susceptibility to Leishmania donovani, the etiological agent of VL, is controlled by Slc11a1 (formerly Nramp1). We therefore examined polymorphisms at SLC11A1 in 59 multicase families of VL from the high-incidence Masalit tribe in Sudan. Multipoint nonparametric analysis in ALLEGRO shows a significant linkage across SLC11A1 (Z lr scores 2.38-2.55; 0.008pPp0.012; information content 0.88). The extended transmission disequilibrium test shows biased transmission of alleles at 5 0 polymorphisms in the promoter (P ¼ 0.0145), exon 3 (P ¼ 0.0037) and intron 4 (P ¼ 0.0049), and haplotypes formed by them (P ¼ 0.0089), but not for 3 0 polymorphisms at exon 15 or the 3 0 UTR. Stepwise logistic regression analysis using a case/pseudo-control data set derived from the 59 families was consistent with main effects contributed by the intron 4 469 þ 14G/C polymorphism. Although the two alleles for 469 þ 14G/C lie on haplotypes carrying different alleles for the functional promoter GT n polymorphism, the latter did not itself contribute separate main effects. Sequence analysis of 36 individuals failed to identify new putative functional polymorphisms in the coding region, intron 1, intron/exon boundaries, intron 4/exon 4a, or in the 3 0 UTR. One novel promoter polymorphism (-86G/A) was located within a putative nuclear factor kappa B binding site that could be functional. Further work will determine whether additional polymorphisms occur upstream in the promoter, which could be in linkage disequilibrium with the intron 4 polymorphism. These studies contribute to knowledge of the role of SLC11A1 in infectious disease.

Research paper thumbnail of Candidate gene analysis supports a role for polymorphisms at TCF7L2 as risk factors for type 2 diabetes in Sudan

Journal of Diabetes & Metabolic Disorders, 2015

Background: Genetic susceptibility to type 2 diabetes (T2D) is multifactorial. A growing number o... more Background: Genetic susceptibility to type 2 diabetes (T2D) is multifactorial. A growing number of genes have been identified as risk factors for T2D across multiple ethnicities in trans-ancestry meta-analysis of large-scale genome-wide association studies. Few studies have looked at these genes in Sub-Saharan African populations. This study was undertaken to look for associations between T2D and single nucleotide polymorphisms (SNPs) in a number of the top candidate genes in a selected Sudanese population. Methods: A total 240 T2D cases and 128 unrelated healthy control subjects were included in this study. Age, sex, weight and height were recorded, blood pressure and biochemical profiles of glucose and lipids were analysed. Single nucleotide polymorphism (SNP) genotyping was performed using the Sequenom MassARRAY® system. Fourteen SNPs were selected across 7 genes: CAPN10 (rs2975760 and rs5030952), PPARG (rs17036314 and rs1801282), IGF2BP2 (rs4402960 and rs1470579), CDKAL1 (rs9465871), HHEX (rs1111875), TCF7L2 (rs7903146, rs11196205 and rs12255372), and KCNJ11 (rs5215, rs1800467 and rs5219). Allelic and haplotype association analyses were performed under additive models in PLINK. P ≤ 0.007 (=0.05/7 genes) was the P-value required to achieve correction for multiple testing. Results: A significant genetic association between the SNPs rs7903146 (odds ratio 1.69, 95 % confidence interval 1.21-2.38, P = 0.002) and rs12255372 (odds ratio 1.70, 95 % confidence interval 1.20-2.41, P = 0.003) at TCF7L2 and T2D was found in Sudanese population. These associations were retained after adjusting for age, sex and BMI (e.g. rs7903146: odds ratio 1.70, P adj:age/sex/BMI = 0.005). The strongest haplotype association (odds ratio 2.24; P adj:age/sex/BMI = 0.0003) comprised the two point haplotype T_C across rs7903146 and rs11196205. Stepwise logistic regression demonstrated that SNP rs7903146 added significant main effects to rs11196205 or rs12255372, whereas the reverse was not true, indicating that the main effect for association with T2D in this population is most strongly tagged by SNP rs7903146. Adjusted analyses also provided support for protection from T2D associated with minor alleles at SNPs rs2975760 at CAPN10 (odds ratio 0.44, 95 % confidence interval 0.20-0.97, P adj:age/sex/BMI = 0.042) and rs1111876 at HHEX (odds ratio 0.60, 95 % confidence interval 0.39-0.93, P adj:age/sex/BMI = 0.022). Conclusions: Multiethnic associations between T2D and SNPs at TCF7L2, CAPN10 and HHEX extend to Sub-Saharan Africa, specifically Sudan.

Research paper thumbnail of IFNG and IFNGR1 gene polymorphisms and susceptibility to post-kala-azar dermal leishmaniasis in Sudan

Research paper thumbnail of The Tianjin Statement of Global Young Scientists at the Annual Meeting of New Champions of the World Economic Forum 2008

As young scientists from all five continents, we are passionate about science, and we are passion... more As young scientists from all five continents, we are passionate about science, and we are passionate about science contributing to a better world. We wish to enhance the contribution that we can make to science and that science can make to society. Science and technology play an important role in addressing the challenges we face today, from reducing hunger and poverty, finding a cure for diseases such as malaria, to protecting the environment. We believe that these are universal aspirations, shared by young scientists around the world and deserving global solutions. Actions are required at local, national and international levels by young scientists themselves, senior scientists, science policy makers, politicians, the private and civil society sectors and the general public.

Research paper thumbnail of Additional file 12: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Additional Table ST6: Results of linear regression analysis investigating the effect of age, gend... more Additional Table ST6: Results of linear regression analysis investigating the effect of age, gender and parasite density on logged antibody levels to AMA1, MSP1, MSP2, NANP and IgE. Results of linear regression analysis investigating the effect of age, gender and parasite density using combined data for each antibody measured in this study. This is an extension to that shown in the main text and is a reduced dataset as not all sites provided parasitaemia data.

Research paper thumbnail of EBV Associated Breast Cancer Whole Methylome Analysis Reveals Viral and Developmental Enriched Pathways

Frontiers in oncology, 2018

Breast cancer (BC) ranks among the most common cancers in Sudan and worldwide with hefty toll on ... more Breast cancer (BC) ranks among the most common cancers in Sudan and worldwide with hefty toll on female health and human resources. Recent studies have uncovered a common BC signature characterized by low frequency of oncogenic mutations and high frequency of epigenetic silencing of major BC tumor suppressor genes. Therefore, we conducted a pilot genome-wide methylome study to characterize aberrant DNA methylation in breast cancer. Differential methylation analysis between primary tumor samples and normal samples from healthy adjacent tissues yielded 20,188 differentially methylated positions (DMPs), which is further divided into 13,633 hypermethylated sites corresponding to 5339 genes and 6,555 hypomethylated sites corresponding to 2811 genes. Moreover, bioinformatics analysis revealed epigenetic dysregulation of major developmental pathways including hippo signaling pathway. We also uncovered many clues to a possible role for EBV infection in BC. Our results clearly show the utili...

Research paper thumbnail of The Association of High Prevalence of Trophozoites in Peripheral Blood with Lower Antibody Response toP. falciparumInfected Erythrocytes among Asymptomatic Children in Sudan

Mediators of Inflammation, 2016

Background. The most prominent variant surface antigens (VSAs) ofPlasmodium falciparumare the var... more Background. The most prominent variant surface antigens (VSAs) ofPlasmodium falciparumare the var gene-encodedPlasmodium falciparumerythrocyte membrane protein 1 (PfEMP1) family, which serves as a parasite-sequestering ligand to endothelial cells. In this study we have examined the antibody reactivity of autologous plasma from symptomatic and asymptomatic malaria infected children against the infected erythrocytes’ surface antigens using flow cytometry.Methods. Ethidium-bromide-labelled erythrocytic mature forms ofP. falciparumparasites obtained from symptomatic and asymptomatic children were sequentially incubated with autologous plasma and fluorescein isothiocyanate-conjugated (FITC) antihuman IgG. Plasma antibody reactivity was detected by flow cytometry.Results. Asymptomatic children had more prevalence of trophozoites in peripheral blood (66%) compared to symptomatic children (16%),p=0.002. The mean percentage of infected RBCs reacting with autologous sera was 89.78 among sympt...

Research paper thumbnail of Transmission ofPlasmodium vivaxin Duffy-negative individuals in central Sudan

Transactions of The Royal Society of Tropical Medicine and Hygiene, 2016

Due to the recently observed rise in Plasmodium vivax incidence in Sudan and reported transmissio... more 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. 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. Forty eight (38%) were positive for P. vivax infection by PCR. Four patients (8.3%) were homozygous Duffy-negative. These results confirm that P. vivax can infect Duffy-negative individuals, suggesting alternative mechanisms to bind and invade erythrocytes.

Research paper thumbnail of Methylome analysis reveals dysregulated developmental and viral pathways in breast cancer

Background Breast cancer (BC) ranks among the most common cancers in Sudan and worldwide with hef... more Background Breast cancer (BC) ranks among the most common cancers in Sudan and worldwide with hefty toll on female health and human resources. Recent studies have uncovered a common BC signature characterized by low frequency of oncogenic mutations and high frequency of epigenetic silencing of major BC tumor suppressor genes. Therefore, we conducted a genome-wide methylome study to characterize aberrant DNA methylation in breast cancer. Results Differential methylation analysis between primary tumor samples and normal samples from healthy adjacent tissues yielded 20188 differentially methylated positions (DMPs), which is further divided into 13633 hypermethylated sites corresponding to 5339 genes and 6555 hypomethylated sites corresponding to 2811 genes. Moreover, bioinformatics analysis revealed epigenetic dysregulation of major developmental pathways including hippo signaling pathway. We also uncovered many clues to a possible role for EBV infection in BC Conclusion Our results cl...

Research paper thumbnail of Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways

Frontiers in Genetics, 2015

Research paper thumbnail of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Malaria Journal, 2015

This file contains Additional Table ST6: Results of linear regression analysis investigating the ... more This file contains Additional Table ST6: Results of linear regression analysis investigating the effect of age, gender and parasite density* on logged antibody levels to AMA1, MSP1, MSP2, NANP and IgE. Results shown as betas, which indicate the direction of effect of the clinical covariate on antibody levels. Beta<0 indicate a decrease in antibody levels and beta>0 indicate an increase in antibody levels. 95% confidence intervals that do not span 0 indicate an effect that is significant at p=0.05. Data from Senegal, Kenya, Sudan and Sri Lanka are not included as parasite density was not recorded at these sites.

Research paper thumbnail of Binding to CSA receptor is associated with asymptomatic and mild malaria: a preliminary study using <i>P.falciparum</i> field isolates from Sudan

African Journal of Clinical and Experimental Microbiology, 2011

Malaria imposes great socioeconomic burden on humanity, and afflicts approximately 90 countries a... more Malaria imposes great socioeconomic burden on humanity, and afflicts approximately 90 countries and territories in the tropical and subtropical regions, almost one half of them are in Africa, South of Sahara. Sequestration of parasitized erythrocytes within the small vessels of vital organs is a key event in the pathogenesis of malaria and responsible of virulence of Plasmodium falciparum parasite. To find out whether the ability of infected red blood cells (IRBCs) to adhere to a specific receptor is a risk factor for developing severe clinical manifestation of the disease, in-vitro cytoadhesion and inhibition experiments were performed on field isolates obtained from five symptomatic and five asymptomatic patients inhabiting Gazira State, Central Sudan. The results showed significant lower levels (p<0.02) of cytoadhesion among asymptomatic compared to symptomatic patients. Percent inhibition by FA6-152, a monoclonal antibody for CD36, was comparable between the two study groups. However, the inhibition by CSA protein was less among symptomatic compared to asymptomatic patients. These results shed light on possible role of CSA receptors expressed on endothelial cells in ameliorating the events associated with the severe phenotype of the disease.

Research paper thumbnail of Loss of balancing selection in the betaS globin locus

BMC medical genetics, Jan 3, 2010

Probably the best example of the rise and maintenance of balancing selection as an evolutionary t... more Probably the best example of the rise and maintenance of balancing selection as an evolutionary trend is the role of S-haemoglobin (HbS - rs334) in protecting from malaria. Yet, the dynamics of such a process remains poorly understood, particularly in relation to different malaria transmission rates and the genetic background of the affected populations. We investigated the association of haemoglobin HbS in protection from clinical episodes of malaria in two populations/villages where malaria is endemic, but mostly presenting in mild clinical forms. Five-hundred and forty-six individuals comprising 65 and 82 families from the Hausa and Massalit villages respectively were genotyped for HbS. Allele and genotype frequencies as well as departure from Hardy-Weinberg Equilibrium were estimated from four-hundred and seventy independent genotypes across different age groups. Age-group frequencies were used to calculate the coefficient-of-fitness and to simulate the expected frequencies in f...

Research paper thumbnail of The Tianjin Statement of Global Young Scientists at the Annual Meeting of New Champions of the World Economic Forum 2008

A s young scientists from all five continents, we are passionate about science, and we are passio... more A s young scientists from all five continents, we are passionate about science, and we are passionate about science contributing to a better world. We wish to enhance the contribution that we can make to science and that science can make to society. Science and technology play an important role in addressing the challenges we face today, from reducing hunger and poverty, finding a cure for diseases such as malaria, to protecting the environment. We believe that these are universal aspirations, shared by young scientists around the world and deserving global solutions. Actions are required at local, national and international levels by young scientists themselves, senior scientists, science policy makers, politicians, the private and civil society sectors and the general public. F or science and young scientists to play the role required in the modern, technological and challenging world, public support is essential. For this support to be fostered, scientists -and especially young s...

Research paper thumbnail of The Time of Young Scientists Response

Research paper thumbnail of Estrogen Receptor 1 Gene (ESR1) rs2234693 Polymorphism and Breast Cancer Risk in Saudi Women

Asian Pacific Journal of Cancer Prevention, 2020

Breast cancer (BC) is a serious health issue, causing changes within the body cells and out of co... more Breast cancer (BC) is a serious health issue, causing changes within the body cells and out of control cell grow (

Research paper thumbnail of Fibroblast growth factor receptor 2 gene (FGFR2) rs2981582T/C polymorphism and susceptibility to breast cancer in Saudi women

Saudi Journal of Biological Sciences, 2021

Fibroblast growth factor receptor 2 is a protein encoded by FGFR2 gene and plays an important rol... more Fibroblast growth factor receptor 2 is a protein encoded by FGFR2 gene and plays an important role in cellular growth. This study was conducted to investigate a potential association of FGFR2 rs2981582 with breast cancer. DNA was obtained from 137 Formalin-fixed, paraffin-embedded tumors and 98 normal breast tissue samples. Genotypes were carried out with PCR-RFLP. The odds ratio and 95% confidence interval (CI) were used to evaluate the power of the associations. A significant association between FGFR2 rs2981582 C allele and susceptibility to breast cancer was found (p-value < 0.0001, Odds Ratio = 2.3, %95 CI (1.5–3.0). No significant differences in FGFR2 rs2981582 genotypes and alleles distribution among breast patients with different hormonal receptor status (p > 0.05) were detected. However, a significant difference was found in genotypes and alleles distribution in ER+, PR- and HER2 between breast cancer cases and controls. This study showed an association of FGFR2 rs2981...

Research paper thumbnail of Allele Frequency and Genotype Distribution of 9 SNPs in the Kazakh Population

Journal of Pharmacogenomics & Pharmacoproteomics, 2014

The CYP2C9 gene has high genetic polymorphism. The structural gene polymorphisms CYP2C9-R144C (CY... more The CYP2C9 gene has high genetic polymorphism. The structural gene polymorphisms CYP2C9-R144C (CYP2C9*2) and I359L (CYP2C9*3) are the most well-studied. The allele CYP2C9*2 reduces the warfarin dose by 40% for heterozygotes and 68% by homozygotes, and the CYP2C9*3 allele by 40 and 85%, respectively. This polymorphic variant explained 14.5% of the interindividual variability in the dose of warfarin together with non-genetic predictors, such as age, body weight and height [2]. VKORC1 gene The VKORC1 gene on chromosome 16 is one of the major genes associated with effective doses of coumarin anticoagulants. Many mutations are associated with a deficiency in this enzyme. The allelic variant VKORC1 c.-1639G>A determines up to 30% of the variability in warfarin dosage [3-8].

Research paper thumbnail of Interleukin 10 Gene Polymorphisms and Development of Post Kala-Azar Dermal Leishmaniasis in a Selected Sudanese Population

Public Health Genomics, 2009

Background: Post kala-azar dermal leishmaniasis (PKDL) is a cutaneous form of disease that develo... more Background: Post kala-azar dermal leishmaniasis (PKDL) is a cutaneous form of disease that develops at variable times after individuals have received treatment for clinical visceral leishmaniasis (VL). The study aimed to investigate the possible role of interleukin 10 (IL-10) and development of PKDL. Methods: 77 families composed of 41 complete case-parent trios and 36 case-parent pairs from the Masalit ethnic group were genotyped for 3 IL10 promoter polymorphisms: -1082A/G, -819C/T and -592C/A. Results: Single point analysis using the transmission disequilibrium test showed no evidence of association between any of these IL10 promoter single nucleotide polymorphisms (SNPs) and development of PKDL. Haplotype analysis performed using TRANSMIT showed borderline significance between PKDL and the haplotype AA across -592C/A and -1082A/G (p = 0.053). Haplotypes GCC (0.33) and ATA (0.30) were the common haplotypes in this Sudanese population. Allele frequencies for the 3 SNPs differed sig...

Research paper thumbnail of Y Chromosome Lineage- and Village-Specific Genes on Chromosomes 1p22 and 6q27 Control Visceral Leishmaniasis in Sudan

PLoS Genetics, 2007

Familial clustering and ethnic differences suggest that visceral leishmaniasis caused by Leishman... more Familial clustering and ethnic differences suggest that visceral leishmaniasis caused by Leishmania donovani is under genetic control. A recent genome scan provided evidence for a major susceptibility gene on Chromosome 22q12 in the Aringa ethnic group in Sudan. We now report a genome-wide scan using 69 families with 173 affected relatives from two villages occupied by the related Masalit ethnic group. A primary ten-centimorgan scan followed by refined mapping provided evidence for major loci at 1p22 (LOD score 5.65; nominal p ¼ 1.72 3 10 À7 ; empirical p , 1 3 10 À5 ; k S ¼ 5.1) and 6q27 (LOD score 3.74; nominal p ¼ 1.68 3 10 À5 ; empirical p , 1 3 10 À4 ; k S ¼ 2.3) that were Y chromosomelineage and village-specific. Neither village supported a visceral leishmaniasis susceptibility gene on 22q12. The results suggest strong lineage-specific genes due to founder effect and consanguinity in these recently immigrant populations. These chance events in ethnically uniform African populations provide a powerful resource in the search for genes and mechanisms that regulate this complex disease.

Research paper thumbnail of SLC11A1 (formerly NRAMP1) and susceptibility to visceral leishmaniasis in The Sudan

European Journal of Human Genetics, 2003

Genetic susceptibility to visceral leishmaniasis (VL) is indicated by differences in incidence an... more Genetic susceptibility to visceral leishmaniasis (VL) is indicated by differences in incidence and clinical phenotypes between ethnic groups in Sudan. In mice, innate susceptibility to Leishmania donovani, the etiological agent of VL, is controlled by Slc11a1 (formerly Nramp1). We therefore examined polymorphisms at SLC11A1 in 59 multicase families of VL from the high-incidence Masalit tribe in Sudan. Multipoint nonparametric analysis in ALLEGRO shows a significant linkage across SLC11A1 (Z lr scores 2.38-2.55; 0.008pPp0.012; information content 0.88). The extended transmission disequilibrium test shows biased transmission of alleles at 5 0 polymorphisms in the promoter (P ¼ 0.0145), exon 3 (P ¼ 0.0037) and intron 4 (P ¼ 0.0049), and haplotypes formed by them (P ¼ 0.0089), but not for 3 0 polymorphisms at exon 15 or the 3 0 UTR. Stepwise logistic regression analysis using a case/pseudo-control data set derived from the 59 families was consistent with main effects contributed by the intron 4 469 þ 14G/C polymorphism. Although the two alleles for 469 þ 14G/C lie on haplotypes carrying different alleles for the functional promoter GT n polymorphism, the latter did not itself contribute separate main effects. Sequence analysis of 36 individuals failed to identify new putative functional polymorphisms in the coding region, intron 1, intron/exon boundaries, intron 4/exon 4a, or in the 3 0 UTR. One novel promoter polymorphism (-86G/A) was located within a putative nuclear factor kappa B binding site that could be functional. Further work will determine whether additional polymorphisms occur upstream in the promoter, which could be in linkage disequilibrium with the intron 4 polymorphism. These studies contribute to knowledge of the role of SLC11A1 in infectious disease.

Research paper thumbnail of Candidate gene analysis supports a role for polymorphisms at TCF7L2 as risk factors for type 2 diabetes in Sudan

Journal of Diabetes & Metabolic Disorders, 2015

Background: Genetic susceptibility to type 2 diabetes (T2D) is multifactorial. A growing number o... more Background: Genetic susceptibility to type 2 diabetes (T2D) is multifactorial. A growing number of genes have been identified as risk factors for T2D across multiple ethnicities in trans-ancestry meta-analysis of large-scale genome-wide association studies. Few studies have looked at these genes in Sub-Saharan African populations. This study was undertaken to look for associations between T2D and single nucleotide polymorphisms (SNPs) in a number of the top candidate genes in a selected Sudanese population. Methods: A total 240 T2D cases and 128 unrelated healthy control subjects were included in this study. Age, sex, weight and height were recorded, blood pressure and biochemical profiles of glucose and lipids were analysed. Single nucleotide polymorphism (SNP) genotyping was performed using the Sequenom MassARRAY® system. Fourteen SNPs were selected across 7 genes: CAPN10 (rs2975760 and rs5030952), PPARG (rs17036314 and rs1801282), IGF2BP2 (rs4402960 and rs1470579), CDKAL1 (rs9465871), HHEX (rs1111875), TCF7L2 (rs7903146, rs11196205 and rs12255372), and KCNJ11 (rs5215, rs1800467 and rs5219). Allelic and haplotype association analyses were performed under additive models in PLINK. P ≤ 0.007 (=0.05/7 genes) was the P-value required to achieve correction for multiple testing. Results: A significant genetic association between the SNPs rs7903146 (odds ratio 1.69, 95 % confidence interval 1.21-2.38, P = 0.002) and rs12255372 (odds ratio 1.70, 95 % confidence interval 1.20-2.41, P = 0.003) at TCF7L2 and T2D was found in Sudanese population. These associations were retained after adjusting for age, sex and BMI (e.g. rs7903146: odds ratio 1.70, P adj:age/sex/BMI = 0.005). The strongest haplotype association (odds ratio 2.24; P adj:age/sex/BMI = 0.0003) comprised the two point haplotype T_C across rs7903146 and rs11196205. Stepwise logistic regression demonstrated that SNP rs7903146 added significant main effects to rs11196205 or rs12255372, whereas the reverse was not true, indicating that the main effect for association with T2D in this population is most strongly tagged by SNP rs7903146. Adjusted analyses also provided support for protection from T2D associated with minor alleles at SNPs rs2975760 at CAPN10 (odds ratio 0.44, 95 % confidence interval 0.20-0.97, P adj:age/sex/BMI = 0.042) and rs1111876 at HHEX (odds ratio 0.60, 95 % confidence interval 0.39-0.93, P adj:age/sex/BMI = 0.022). Conclusions: Multiethnic associations between T2D and SNPs at TCF7L2, CAPN10 and HHEX extend to Sub-Saharan Africa, specifically Sudan.

Research paper thumbnail of IFNG and IFNGR1 gene polymorphisms and susceptibility to post-kala-azar dermal leishmaniasis in Sudan

Research paper thumbnail of The Tianjin Statement of Global Young Scientists at the Annual Meeting of New Champions of the World Economic Forum 2008

As young scientists from all five continents, we are passionate about science, and we are passion... more As young scientists from all five continents, we are passionate about science, and we are passionate about science contributing to a better world. We wish to enhance the contribution that we can make to science and that science can make to society. Science and technology play an important role in addressing the challenges we face today, from reducing hunger and poverty, finding a cure for diseases such as malaria, to protecting the environment. We believe that these are universal aspirations, shared by young scientists around the world and deserving global solutions. Actions are required at local, national and international levels by young scientists themselves, senior scientists, science policy makers, politicians, the private and civil society sectors and the general public.

Research paper thumbnail of Additional file 12: of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Additional Table ST6: Results of linear regression analysis investigating the effect of age, gend... more Additional Table ST6: Results of linear regression analysis investigating the effect of age, gender and parasite density on logged antibody levels to AMA1, MSP1, MSP2, NANP and IgE. Results of linear regression analysis investigating the effect of age, gender and parasite density using combined data for each antibody measured in this study. This is an extension to that shown in the main text and is a reduced dataset as not all sites provided parasitaemia data.

Research paper thumbnail of EBV Associated Breast Cancer Whole Methylome Analysis Reveals Viral and Developmental Enriched Pathways

Frontiers in oncology, 2018

Breast cancer (BC) ranks among the most common cancers in Sudan and worldwide with hefty toll on ... more Breast cancer (BC) ranks among the most common cancers in Sudan and worldwide with hefty toll on female health and human resources. Recent studies have uncovered a common BC signature characterized by low frequency of oncogenic mutations and high frequency of epigenetic silencing of major BC tumor suppressor genes. Therefore, we conducted a pilot genome-wide methylome study to characterize aberrant DNA methylation in breast cancer. Differential methylation analysis between primary tumor samples and normal samples from healthy adjacent tissues yielded 20,188 differentially methylated positions (DMPs), which is further divided into 13,633 hypermethylated sites corresponding to 5339 genes and 6,555 hypomethylated sites corresponding to 2811 genes. Moreover, bioinformatics analysis revealed epigenetic dysregulation of major developmental pathways including hippo signaling pathway. We also uncovered many clues to a possible role for EBV infection in BC. Our results clearly show the utili...

Research paper thumbnail of The Association of High Prevalence of Trophozoites in Peripheral Blood with Lower Antibody Response toP. falciparumInfected Erythrocytes among Asymptomatic Children in Sudan

Mediators of Inflammation, 2016

Background. The most prominent variant surface antigens (VSAs) ofPlasmodium falciparumare the var... more Background. The most prominent variant surface antigens (VSAs) ofPlasmodium falciparumare the var gene-encodedPlasmodium falciparumerythrocyte membrane protein 1 (PfEMP1) family, which serves as a parasite-sequestering ligand to endothelial cells. In this study we have examined the antibody reactivity of autologous plasma from symptomatic and asymptomatic malaria infected children against the infected erythrocytes’ surface antigens using flow cytometry.Methods. Ethidium-bromide-labelled erythrocytic mature forms ofP. falciparumparasites obtained from symptomatic and asymptomatic children were sequentially incubated with autologous plasma and fluorescein isothiocyanate-conjugated (FITC) antihuman IgG. Plasma antibody reactivity was detected by flow cytometry.Results. Asymptomatic children had more prevalence of trophozoites in peripheral blood (66%) compared to symptomatic children (16%),p=0.002. The mean percentage of infected RBCs reacting with autologous sera was 89.78 among sympt...

Research paper thumbnail of Transmission ofPlasmodium vivaxin Duffy-negative individuals in central Sudan

Transactions of The Royal Society of Tropical Medicine and Hygiene, 2016

Due to the recently observed rise in Plasmodium vivax incidence in Sudan and reported transmissio... more 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. 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. Forty eight (38%) were positive for P. vivax infection by PCR. Four patients (8.3%) were homozygous Duffy-negative. These results confirm that P. vivax can infect Duffy-negative individuals, suggesting alternative mechanisms to bind and invade erythrocytes.

Research paper thumbnail of Methylome analysis reveals dysregulated developmental and viral pathways in breast cancer

Background Breast cancer (BC) ranks among the most common cancers in Sudan and worldwide with hef... more Background Breast cancer (BC) ranks among the most common cancers in Sudan and worldwide with hefty toll on female health and human resources. Recent studies have uncovered a common BC signature characterized by low frequency of oncogenic mutations and high frequency of epigenetic silencing of major BC tumor suppressor genes. Therefore, we conducted a genome-wide methylome study to characterize aberrant DNA methylation in breast cancer. Results Differential methylation analysis between primary tumor samples and normal samples from healthy adjacent tissues yielded 20188 differentially methylated positions (DMPs), which is further divided into 13633 hypermethylated sites corresponding to 5339 genes and 6555 hypomethylated sites corresponding to 2811 genes. Moreover, bioinformatics analysis revealed epigenetic dysregulation of major developmental pathways including hippo signaling pathway. We also uncovered many clues to a possible role for EBV infection in BC Conclusion Our results cl...

Research paper thumbnail of Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways

Frontiers in Genetics, 2015

Research paper thumbnail of Genetic determinants of anti-malarial acquired immunity in a large multi-centre study

Malaria Journal, 2015

This file contains Additional Table ST6: Results of linear regression analysis investigating the ... more This file contains Additional Table ST6: Results of linear regression analysis investigating the effect of age, gender and parasite density* on logged antibody levels to AMA1, MSP1, MSP2, NANP and IgE. Results shown as betas, which indicate the direction of effect of the clinical covariate on antibody levels. Beta<0 indicate a decrease in antibody levels and beta>0 indicate an increase in antibody levels. 95% confidence intervals that do not span 0 indicate an effect that is significant at p=0.05. Data from Senegal, Kenya, Sudan and Sri Lanka are not included as parasite density was not recorded at these sites.

Research paper thumbnail of Binding to CSA receptor is associated with asymptomatic and mild malaria: a preliminary study using <i>P.falciparum</i> field isolates from Sudan

African Journal of Clinical and Experimental Microbiology, 2011

Malaria imposes great socioeconomic burden on humanity, and afflicts approximately 90 countries a... more Malaria imposes great socioeconomic burden on humanity, and afflicts approximately 90 countries and territories in the tropical and subtropical regions, almost one half of them are in Africa, South of Sahara. Sequestration of parasitized erythrocytes within the small vessels of vital organs is a key event in the pathogenesis of malaria and responsible of virulence of Plasmodium falciparum parasite. To find out whether the ability of infected red blood cells (IRBCs) to adhere to a specific receptor is a risk factor for developing severe clinical manifestation of the disease, in-vitro cytoadhesion and inhibition experiments were performed on field isolates obtained from five symptomatic and five asymptomatic patients inhabiting Gazira State, Central Sudan. The results showed significant lower levels (p<0.02) of cytoadhesion among asymptomatic compared to symptomatic patients. Percent inhibition by FA6-152, a monoclonal antibody for CD36, was comparable between the two study groups. However, the inhibition by CSA protein was less among symptomatic compared to asymptomatic patients. These results shed light on possible role of CSA receptors expressed on endothelial cells in ameliorating the events associated with the severe phenotype of the disease.

Research paper thumbnail of Loss of balancing selection in the betaS globin locus

BMC medical genetics, Jan 3, 2010

Probably the best example of the rise and maintenance of balancing selection as an evolutionary t... more Probably the best example of the rise and maintenance of balancing selection as an evolutionary trend is the role of S-haemoglobin (HbS - rs334) in protecting from malaria. Yet, the dynamics of such a process remains poorly understood, particularly in relation to different malaria transmission rates and the genetic background of the affected populations. We investigated the association of haemoglobin HbS in protection from clinical episodes of malaria in two populations/villages where malaria is endemic, but mostly presenting in mild clinical forms. Five-hundred and forty-six individuals comprising 65 and 82 families from the Hausa and Massalit villages respectively were genotyped for HbS. Allele and genotype frequencies as well as departure from Hardy-Weinberg Equilibrium were estimated from four-hundred and seventy independent genotypes across different age groups. Age-group frequencies were used to calculate the coefficient-of-fitness and to simulate the expected frequencies in f...

Research paper thumbnail of The Tianjin Statement of Global Young Scientists at the Annual Meeting of New Champions of the World Economic Forum 2008

A s young scientists from all five continents, we are passionate about science, and we are passio... more A s young scientists from all five continents, we are passionate about science, and we are passionate about science contributing to a better world. We wish to enhance the contribution that we can make to science and that science can make to society. Science and technology play an important role in addressing the challenges we face today, from reducing hunger and poverty, finding a cure for diseases such as malaria, to protecting the environment. We believe that these are universal aspirations, shared by young scientists around the world and deserving global solutions. Actions are required at local, national and international levels by young scientists themselves, senior scientists, science policy makers, politicians, the private and civil society sectors and the general public. F or science and young scientists to play the role required in the modern, technological and challenging world, public support is essential. For this support to be fostered, scientists -and especially young s...