48 results on '"Ibrahim, Muntaser E."'
Search Results
2. CMMRD caused by PMS1 mutation in a sudanese consanguineous family
- Author
-
Hamad, Reem S. and Ibrahim, Muntaser E.
- Subjects
Gene mutations -- Health aspects -- Genetic aspects ,Colorectal cancer -- Genetic aspects ,Brain tumors -- Genetic aspects ,Health - Abstract
A consanguineous family of three siblings presented with different early onset pediatric cancers. Whole-exome sequencing of parents DNA revealed a deleterious frameshift mutation in hPMS1 the first to be reported in association to a CMMRD phenotype. Keywords: CMMRD, PMS1, Consanguinity, Cancer, Author(s): Reem S. Hamad[sup.1] and Muntaser E. Ibrahim[sup.1] Main text Germline mutations in Mismatch repair (MMR) genes [1] may result in various hereditary cancer syndromes including Lynch syndrome (LS), Constitutional [...]
- Published
- 2022
- Full Text
- View/download PDF
3. High altitude and pre-eclampsia: Adaptation or protection
- Author
-
Ahmed, Sarah I.Y., Ibrahim, Muntaser E., and Khalil, Eltahir A.G.
- Published
- 2017
- Full Text
- View/download PDF
4. Dispatches from a world in turmoil
- Author
-
Fawaz, Mona, Scharifker, Benjamin R., Moraes R., Mónica, Ibrahim, Muntaser E., Moradi, Sharif, Medina, Ernesto, and Maziak, Wasim
- Subjects
Scientists -- Social aspects -- Political activity -- Personal narratives ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
Scientists reflect on a year of civil unrest. Writing from Syria, Bolivia, Sudan, Iran, Chile, Ecuador, Lebanon, Venezuela, Hong Kong and Catalonia, correspondents tell of altered priorities, day-to-day challenges and hope in the dark times. Scientists from Syria, Bolivia, Sudan, Iran, Chile, Ecuador, Lebanon, Venezuela, Hong Kong and Catalonia reflect on a year of civil unrest., Author(s): Mona Fawaz, Benjamin R. Scharifker, Mónica Moraes R., Muntaser E. Ibrahim, Sharif Moradi, Ernesto Medina, Wasim Maziak, Mai Har Sham, Cecilia Hidalgo, Joan Martínez Alier Author Affiliations: Dispatches from [...]
- Published
- 2019
- Full Text
- View/download PDF
5. Follicular Helper and Regulatory T Cells Drive the Development of Spontaneous Epstein–Barr Virus Lymphoproliferative Disorder.
- Author
-
Ahmed, Elshafa Hassan, Lustberg, Mark, Hale, Claire, Sloan, Shelby, Mao, Charlene, Zhang, Xiaoli, Ozer, Hatice Gulcin, Schlotter, Sarah, Smith, Porsha L., Jeney, Frankie, Chan, Wing Keung, Harrington, Bonnie K., Weigel, Christoph, Brooks, Eric, Klimaszewski, Haley L., Oakes, Christopher C., Abebe, Tamrat, Ibrahim, Muntaser E., Alinari, Lapo, and Behbehani, Gregory K.
- Subjects
BIOMARKERS ,CYTOKINES ,B cells ,ANIMAL experimentation ,IMMUNOCOMPROMISED patients ,REGULATORY T cells ,MYELOID-derived suppressor cells ,EPSTEIN-Barr virus ,RESEARCH funding ,LYMPHOPROLIFERATIVE disorders ,T cells ,IMMUNOLOGIC memory ,T helper cells ,MICE - Abstract
Simple Summary: Over 90% of the adult population worldwide is infected with the Epstein–Barr virus (EBV). While EBV infection is associated with the development of lymphoproliferative disorders (EBV-LPD) in people with weakened immune systems, only ~20% of immunodeficient individuals develop EBV-LPD. Such clinical heterogeneity may reflect host variables that increase the risk of developing EBV-LPD. Immunodeficient mice engrafted with blood cells from EBV+ individuals develop spontaneous EBV-LPD of human B-cell origin with similar heterogeneity observed in humans. Our study aimed to investigate differences between the model's lymphoma producers (High-Incidence, HI donors) and non-lymphoma producers (No-Incidence, NI donors). HI donors showed high levels of T follicular helper (Tfh), regulatory T cells (Treg), and myeloid-derived suppressor cells compared to NI donors. Depletion of Tfh or Treg subsets delays or prevents EBV-LPD in this model. Our results reveal potential biomarkers that may help classify vulnerable patients at risk for developing EBV-LPD. Epstein–Barr virus (EBV) is a ubiquitous herpes virus associated with various cancers. EBV establishes latency with life-long persistence in memory B-cells and can reactivate lytic infection placing immunocompromised individuals at risk for EBV-driven lymphoproliferative disorders (EBV-LPD). Despite the ubiquity of EBV, only a small percentage of immunocompromised patients (~20%) develop EBV-LPD. Engraftment of immunodeficient mice with peripheral blood mononuclear cells (PBMCs) from healthy EBV-seropositive donors leads to spontaneous, malignant, human B-cell EBV-LPD. Only about 20% of EBV+ donors induce EBV-LPD in 100% of engrafted mice (High-Incidence, HI), while another 20% of donors never generate EBV-LPD (No-Incidence, NI). Here, we report HI donors to have significantly higher basal T follicular helper (Tfh) and regulatory T-cells (Treg), and depletion of these subsets prevents/delays EBV-LPD. Transcriptomic analysis of CD4+ T cells from ex vivo HI donor PBMC revealed amplified cytokine and inflammatory gene signatures. HI vs. NI donors showed a marked reduction in IFNγ production to EBV latent and lytic antigen stimulation. In addition, we observed abundant myeloid-derived suppressor cells in HI donor PBMC that decreased CTL proliferation in co-cultures with autologous EBV+ lymphoblasts. Our findings identify potential biomarkers that may identify individuals at risk for EBV-LPD and suggest possible strategies for prevention. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
6. Case report of a novel homozygous splice site mutation in PLA2G6 gene causing infantile neuroaxonal dystrophy in a Sudanese family
- Author
-
Elsayed, Liena E. O., Mohammed, Inaam N., Hamed, Ahlam A. A., Elseed, Maha A., Salih, Mustafa A. M., Yahia, Ashraf, Siddig, Rayan A., Amin, Mutaz, Koko, Mahmoud, Elbashir, Mustafa I., Ibrahim, Muntaser E., Brice, Alexis, Ahmed, Ammar E., and Stevanin, Giovanni
- Published
- 2018
- Full Text
- View/download PDF
7. Genetic and Functional Evidence Implicating "DLL1" as the Gene That Influences Susceptibility to Visceral Leishmaniasis at Chromosome 6q27
- Author
-
Fakiola, Michaela, Miller, E. Nancy, Fadl, Manal, Mohamed, Hiba S., Jamieson, Sarra E., Francis, Richard W., Cordell, Heather J., Peacock, Christopher S., Raju, Madhuri, Khalil, Eltahir A., Elhassan, Ahmed, Musa, Ahmed M., Silveira, Fernando, Shaw, Jeffrey J., Sundar, Shyam, Jeronimo, Selma M. B., Ibrahim, Muntaser E., and Blackwell, Jenefer M.
- Published
- 2011
- Full Text
- View/download PDF
8. Relationship of the Sickle Cell Gene to the Ethnic and Geographic Groups Populating the Sudan
- Author
-
Mohammed, Abdelrahim O., Attalla, Bekhieta, Bashir, Fathya M.K., Ahmed, Fatima E., Hassan, Ahmed M. El, Ibnauf, Gafar, Jiang, Weiying, Cavalli-Sforza, Luigi L., Karrar, Zein Al Abdin, and Ibrahim, Muntaser E.
- Published
- 2006
9. The Spike Protein of SARS-coV2 19B (S) Clade Mirrors Critical Features of Viral Adaptation and Coevolution.
- Author
-
Hussein, Bidour K., Ibrahium, Omnia M., Alamin, Marwa F., Ahmed, Lamees A. M., Abuswar, Safa A. E., Abdelraheem, Mohammed H., and Ibrahim, Muntaser E.
- Subjects
SARS-CoV-2 ,MIRROR neurons ,ANIMAL diversity ,COLD adaptation ,COEVOLUTION ,VIRAL transmission ,VIRAL proteins - Abstract
Pathogens including viruses evolve in tandem with diversity in their animal and human hosts. For SARS-coV2, the focus is generally for understanding such coevolution on the virus spike protein, since it demonstrates high mutation rates compared to other genome regions, particularly in the receptor-binding domain (RBD). Viral sequences of the SARS-coV2 19B (S) clade and variants of concern from different continents were investigated, with a focus on the A.29 lineage, which presented with different mutational patterns within the 19B (S) lineages in order to learn more about how SARS-coV2 may have evolved and adapted to widely diverse populations globally. Results indicated that SARS-coV2 went through evolutionary constrains and intense selective pressure, particularly in Africa. This was manifested in a departure from neutrality with excess nonsynonymous mutations and a negative Tajima D consistent with rapid expansion and directional selection as well as deletion and deletion–frameshifts in the N-terminal domain (NTD region) of the spike protein. In conclusion, we hypothesize that viral transmission during epidemics through populations of diverse genomic structures and marked complexity may be a significant factor for the virus to acquire distinct patterns of mutations within these populations in order to ensure its survival and fitness, explaining the emergence of novel variants and strains. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
10. Role of pH in Regulating Cancer Pyrimidine Synthesis.
- Author
-
Alqahtani, Saad Saeed, Koltai, Tomas, Ibrahim, Muntaser E., Bashir, Adil H. H., Alhoufie, Sari T. S., Ahmed, Samrein B. M., Molfetta, Daria Di, Carvalho, Tiago M. A., Cardone, Rosa Angela, Reshkin, Stephan Joel, Hifny, Abdelhameed, Ahmed, Mohamed E., and Alfarouk, Khalid Omer
- Subjects
NUCLEOTIDE synthesis ,TUMOR suppressor genes ,PYRIMIDINES ,MACROMOLECULES - Abstract
Replication is a fundamental aspect of cancer, and replication is about reproducing all the elements and structures that form a cell. Among them are DNA, RNA, enzymes, and coenzymes. All the DNA is doubled during each S (synthesis) cell cycle phase. This means that six billion nucleic acids must be synthesized in each cycle. Tumor growth, proliferation, and mutations all depend on this synthesis. Cancer cells require a constant supply of nucleotides and other macromolecules. For this reason, they must stimulate de novo nucleotide synthesis to support nucleic acid provision. When deregulated, de novo nucleic acid synthesis is controlled by oncogenes and tumor suppressor genes that enable increased synthesis and cell proliferation. Furthermore, cell duplication must be achieved swiftly (in a few hours) and in the midst of a nutrient-depleted and hypoxic environment. This also means that the enzymes participating in nucleic acid synthesis must work efficiently. pH is a critical factor in enzymatic efficiency and speed. This review will show that the enzymatic machinery working in nucleic acid synthesis requires a pH on the alkaline side in most cases. This coincides with many other pro-tumoral factors, such as the glycolytic phenotype, benefiting from an increased intracellular pH. An increased intracellular pH is a perfect milieu for high de novo nucleic acid production through optimal enzymatic performance. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
11. p53 Codon 72 arginine/proline polymorphism and cancer in Sudan
- Author
-
Eltahir, Huda A., Adam, Ameera A. M., Yahia, Zeinab A., Ali, Noon F., Mursi, Dalia M., Higazi, Ashraaf M., Eid, Nahid A., Elhassan, Ahmed M., Mohammed, Hiba S., and Ibrahim, Muntaser E.
- Published
- 2012
- Full Text
- View/download PDF
12. Y-chromosome variation among Sudanese: restricted gene flow, concordance with language, geography, and history
- Author
-
Hassan, Hisham Y., Underhill, Peter A., Cavalli-Sforza, Luca L., and Ibrahim, Muntaser E.
- Subjects
Genetic research -- Analysis ,Geography -- Analysis ,Anthropology/archeology/folklore - Abstract
We study the major levels of Y-chromosome haplogroup variation in 15 Sudanese populations by typing major Y-haplogroups in 445 unrelated males representing the three linguistic families in Sudan. Our analysis shows Sudanese populations fall into haplogroups A, B, E, F, I, J, K, and R in frequencies of 16.9, 7.9, 34.4, 3.1, 1.3, 22.5, 0.9, and 13% respectively. Haplogroups A, B, and E occur mainly in Nilo-Saharan speaking groups including Nilotics, Fur, Borgu, and Masalit; whereas haplogroups F, I, J, K, and R are more frequent among Afro-Asiatic speaking groups including Arabs, Beja, Copts, and Hausa, and Niger-Congo speakers from the Fulani ethnic group. Mantel tests reveal a strong correlation between genetic and linguistic structures (r = 0.31, P = 0.007), and a similar correlation between genetic and geographic distances (r = 0.29, P = 0.025) that appears after removing nomadic pastoralists of no known geographic locality from the analysis. The bulk of genetic diversity appears to be a consequence of recent migrations and demographic events mainly from Asia and Europe, evident in a higher migration rate for speakers of Afro-Asiatic as compared with the Nilo-Saharan family of languages, and a generally higher effective population size for the former. The data provide insights not only into the history of the Nile Valley, but also in part to the history of Africa and the area of the Sahel. KEY WORDS Sudan; Nile Valley; Y-chromosome; haplogroups
- Published
- 2008
13. Individualized Medicine in Africa: Bringing the Practice Into the Realms of Population Heterogeneity.
- Author
-
Hussein, Ayman A., Hamad, Reem, Newport, Melanie J., and Ibrahim, Muntaser E.
- Subjects
INDIVIDUALIZED medicine ,PHARMACOGENOMICS ,MEDICAL scientists ,HETEROGENEITY ,MEDICAL care ,CLINICAL medicine - Abstract
The declared aim of "personalized", "stratified" or "precision" approaches is to place individual variation, as ascertained through genomic and various other biomarkers, at the heart of Scientific Medicine using it to predict risk of disease or response to therapy and to tailor interventions and target therapies so as to maximize benefit and minimize risk for individual patients and efficiency for the health care system overall. It is often contrasted to current practices for which the scientific base is rooted in concepts of a "universal biology" and a "typical" or "average patient" and in which variation is ignored. Yet both approaches equally overlook the hierarchical nature of human variation and the critical importance of differences between populations. Impact of genetic heterogeneity has to be seen within that context to be meaningful and subsequently useful. In Africa such complexity is compounded by the high effective size of its populations, their diverse histories and the diversity of the environmental terrains they occupy, rendering analysis of gene environment interactions including the establishment of phenotype genotype correlations even more cumbersome. Henceforth "Individualized" methods and approaches can only magnify the shortcomings of universal approaches if adopted without due regard to these complexities. In the current perspective we review examples of potential hurdles that may confront biomedical scientists and analysts in genomic medicine in clinical and public health genomics in Africa citing specific examples from the current SARS-COV2 pandemic and the challenges of establishing reference biobanks and pharmacogenomics reference values. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
14. Of mitochondrion and COVID-19.
- Author
-
Alfarouk, Khalid Omer, Alhoufie, Sari T. S., Hifny, Abdelhameed, Schwartz, Laurent, Alqahtani, Ali S., Ahmed, Samrein B. M., Alqahtani, Ali M., Alqahtani, Saad S., Muddathir, Abdel Khalig, Ali, Heyam, Bashir, Adil H. H., Ibrahim, Muntaser E., Greco, Maria Raffaella, Cardone, Rosa A., Harguindey, Salvador, and Reshkin, Stephan Joel
- Subjects
MITOCHONDRIA ,COVID-19 ,COVID-19 treatment ,CYTOKINE release syndrome ,SYMPTOMS ,VIRUS diseases - Abstract
COVID-19, a pandemic disease caused by a viral infection, is associated with a high mortality rate. Most of the signs and symptoms, e.g. cytokine storm, electrolytes imbalances, thromboembolism, etc., are related to mitochondrial dysfunction. Therefore, targeting mitochondrion will represent a more rational treatment of COVID-19. The current work outlines how COVID-19's signs and symptoms are related to the mitochondrion. Proper understanding of the underlying causes might enhance the opportunity to treat COVID-19. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
15. Genetics and visceral leishmaniasis in the Sudan: seeking a link
- Author
-
Blackwell, Jenefer M., Mohamed, Hiba S., and Ibrahim, Muntaser E.
- Published
- 2004
- Full Text
- View/download PDF
16. Pathogenesis and Management of COVID-19.
- Author
-
Alfarouk, Khalid O., AlHoufie, Sari T. S., Ahmed, Samrein B. M., Shabana, Mona, Ahmed, Ahmed, Alqahtani, Saad S., Alqahtani, Ali S., Alqahtani, Ali M., Ramadan, AbdelRahman M., Ahmed, Mohamed E., Ali, Heyam S., Bashir, Adil, Devesa, Jesus, Cardone, Rosa A., Ibrahim, Muntaser E., Schwartz, Laurent, and Reshkin, Stephan J.
- Subjects
COVID-19 ,PATHOGENESIS ,MULTIPLE organ failure ,CYTOKINE release syndrome ,SARS-CoV-2 - Abstract
COVID-19, occurring due to SARS-COV-2 infection, is the most recent pandemic disease that has led to three million deaths at the time of writing. A great deal of effort has been directed towards altering the virus trajectory and/or managing the interactions of the virus with its subsequent targets in the human body; these interactions can lead to a chain reaction-like state manifested by a cytokine storm and progress to multiple organ failure. During cytokine storms the ratio of pro-inflammatory to anti-inflammatory mediators is generally increased, which contributes to the instigation of hyper-inflammation and confers advantages to the virus. Because cytokine expression patterns fluctuate from one person to another and even within the same person from one time to another, we suggest a road map of COVID-19 management using an individual approach instead of focusing on the blockbuster process (one treatment for most people, if not all). Here, we highlight the biology of the virus, study the interaction between the virus and humans, and present potential pharmacological and non-pharmacological modulators that might contribute to the global war against SARS-COV-2. We suggest an algorithmic roadmap to manage COVID-19. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
17. Candidate malaria susceptibility/protective SNPs in hospital and population-based studies: the effect of sub-structuring
- Author
-
Rockett Kirk A, Mohamed Hiba S, Elzein Abier M, Hussein Aymen A, Eid Nahid A, Kwiatkowski Dominic P, and Ibrahim Muntaser E
- Subjects
Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Populations of East Africa including Sudan, exhibit some of the highest indices of genetic diversity in the continent and worldwide. The current study aims to address the possible impact of population structure and population stratification on the outcome of case-control association-analysis of malaria candidate-genes in different Sudanese populations, where the pronounced genetic heterogeneity becomes a source of concern for the potential effect on the studies outcome. Methods A total of 72 SNPs were genotyped using the Sequenom® iPLEX Gold assay in 449 DNA samples that included; cases and controls from two village populations, malaria patients and out-patients from the area of Sinnar and additional controls consisting of healthy Nilo-Saharan speaking individuals. The population substructure was estimated using the Structure 2.2 programme. Results & Discussion The Hardy-Weinberg Equilibrium values were generally within expectation in Hausa and Massalit. However, in the Sinnar area there was a notable excess of homozygosity, which was attributed to the Whalund effect arising from population amalgamation within the sample. The programme STRUCTURE revealed a division of both Hausa and Massalit into two substructures with the partition in Hausa more pronounced than in Massalit; In Sinnar there was no defined substructure. More than 25 of the 72 SNPs assayed were informative in all areas. Some important SNPs were not differentially distributed between malaria cases and controls, including SNPs in CD36 and NOS2. A number of SNPs showed significant p-values for differences in distribution of genotypes between cases and controls including: rs1805015 (in IL4R1) (P = 0.001), rs17047661 (in CR1) (P = 0.02) and rs1800750 (TNF-376)(P = 0.01) in the hospital samples; rs1050828 (G6PD+202) (P = 0.02) and rs1800896 (IL10-1082) (P = 0.04) in Massalit and rs2243250 (IL4-589) (P = 0.04) in Hausa. Conclusions The difference in population structure partly accounts for some of these significant associations, and the strength of association proved to be sensitive to all levels of sub-structuring whether in the hospital or population-based study.
- Published
- 2010
- Full Text
- View/download PDF
18. Loss of balancing selection in the βS globin locus
- Author
-
Ishag Hani B, Khalil Eltahir AG, Elhassan Ibrahim M, Elzein Abeir M, Almugtaba Ibrahim A, Hussain Ayman A, Salih Niven A, Mohammed Hiba S, Kwiatkowski Dominic, and Ibrahim Muntaser E
- Subjects
Internal medicine ,RC31-1245 ,Genetics ,QH426-470 - Abstract
Abstract Background 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. Methods 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 future generations. Results Genotype frequencies were within Hardy-Weinberg expectations in Hausa and Massalit in the total sample set but not within the different age groups. There was a trend for a decrease of the HbS allele frequency in Hausa and an increase of frequency in Massalit. Although the HbS allele was able to confer significant protection from the clinical episodes of malaria in the two populations, as suggested by the odds ratios, the overall relative fitness of the HbS allele seems to have declined in Hausa. Conclusions Such loss of balancing selection could be due to a combined effect of preponderance of non-clinical malaria in Hausa, and the deleterious effect of the homozygous HbS under circumstances of endogamy.
- Published
- 2010
- Full Text
- View/download PDF
19. Genetic diversity of the Sudanese: insights on origin and implications for health.
- Author
-
Ibrahim, Muntaser E
- Published
- 2021
- Full Text
- View/download PDF
20. Novel Homozygous Missense Mutation in the ARG1 Gene in a Large Sudanese Family.
- Author
-
Elsayed, Liena E. O., Mohammed, Inaam N., Hamed, Ahlam A. A., Elseed, Maha A., Salih, Mustafa A. M., Yahia, Ashraf, Abubaker, Rayan, Koko, Mahmoud, Abd Allah, Amal S. I., Elbashir, Mustafa I., Ibrahim, Muntaser E., Brice, Alexis, Ahmed, Ammar E., and Stevanin, Giovanni
- Subjects
GENETIC mutation ,MISSENSE mutation ,GENETIC testing ,PROTEIN domains ,EPILEPSY ,FAMILIAL spastic paraplegia - Abstract
Background: Arginases catalyze the last step in the urea cycle. Hyperargininemia, a rare autosomal-recessive disorder of the urea cycle, presents after the first year of age with regression of milestones and evolves gradually into progressive spastic quadriplegia and cognitive dysfunction. Genetic studies reported various mutations in the ARG1 gene that resulted in hyperargininemia due to a complete or partial loss of arginase activity. Case Presentation: Five patients from an extended highly consanguineous Sudanese family presented with regression of the acquired milestones, spastic quadriplegia, and mental retardation. The disease onset ranged from 1 to 3 years of age. Two patients had epileptic seizures and one patient had stereotypic clapping. Genetic testing using whole-exome sequencing, done for the patients and a healthy parent, confirmed the presence of a homozygous novel missense variant in the ARG1 gene [GRCh37 (NM_001244438.1): exon 4: g.131902487T>A, c.458T>A, p.(Val153Glu)]. The variant was predicted pathogenic by five algorithms and affected a highly conserved amino acid located in the protein domain ureohydrolase, arginase subgroup. Sanger sequencing of 13 sampled family members revealed complete co-segregation between the variant and the disease distribution in the family in line with an autosomal-recessive mode of inheritance. Biochemical analysis confirmed hyperargininemia in five patients. Conclusion: This study reports the first Sudanese family with ARG1 mutation. The reported variant is a loss-of-function missense mutation. Its pathogenicity is strongly supported by the clinical phenotype, the computational functional impact prediction, the complete co-segregation with the disease, and the biochemical assessment. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
21. Host genetic susceptibility to mycetoma.
- Author
-
Ali, Rayan S., Newport, Melanie J., Bakhiet, Sahar Mubarak, Ibrahim, Muntaser E., and Fahal, Ahmed Hassan
- Subjects
MYCOSES ,DENTAL technology ,GENETIC code ,IMMUNOSENESCENCE ,TROPICAL medicine ,SEX hormones ,IMMUNE system - Abstract
Mycetoma is one of the badly neglected tropical diseases, characterised by subcutaneous painless swelling, multiple sinuses, and discharge containing aggregates of the infecting organism known as grains. Risk factors conferring susceptibility to mycetoma include environmental factors and pathogen factors such as virulence and the infecting dose, in addition to host factors such as immunological and genetic predisposition. Epidemiological evidence suggests that host genetic factors may regulate susceptibility to mycetoma and other fungal infections, but they are likely to be complex genetic traits in which multiple genes interact with each other and environmental factors, as well as the pathogen, to cause disease. This paper reviews what is known about genetic predisposition to fungal infections that might be relevant to mycetoma, as well as all studies carried out to explore host genetic susceptibility to mycetoma. Most studies were investigating polymorphisms in candidate genes related to the host immune response. A total of 13 genes had allelic variants found to be associated with mycetoma, and these genes lie in different pathways and systems such as innate and adaptive immune systems, sex hormone biosynthesis, and some genes coding for host enzymes. None of these studies have been replicated. Advances in genomic science and the supporting technology have paved the way for large-scale genome-wide association and next generation sequencing (NGS) studies, underpinning a new strategy to systematically interrogate the genome for variants associated with mycetoma. Dissecting the contribution of host genetic variation to susceptibility to mycetoma will enable the identification of pathways that are potential targets for new treatments for mycetoma and will also enhance the ability to stratify 'at-risk' individuals, allowing the possibility of developing preventive and personalised clinical care strategies in the future. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
22. The Possible Role of Helicobacter pylori in Gastric Cancer and Its Management.
- Author
-
Alfarouk, Khalid O., Bashir, Adil H. H., Aljarbou, Ahmed N., Ramadan, AbdelRahman M., Muddathir, Abdel Khalig, AlHoufie, Sari T. S., Hifny, Abdelhamid, Elhassan, Gamal O., Ibrahim, Muntaser E., Alqahtani, Saad S., AlSharari, Shakir D., Supuran, Claudiu T., Rauch, Cyril, Cardone, Rosa Angela, Reshkin, Stephan J., Fais, Stefano, and Harguindey, Salvador
- Subjects
STOMACH cancer ,HELICOBACTER pylori ,ANAEROBIC bacteria ,CARCINOGENICITY ,BIOLOGY - Abstract
Helicobacter pylori (HP) is a facultative anaerobic bacterium. HP is a normal flora having immuno-modulating properties. This bacterium is an example of a microorganism inducing gastric cancer. Its carcinogenicity depends on bacteria-host related factors. The proper understanding of the biology of HP inducing gastric cancer offers the potential strategy in the managing of HP rather than eradicating it. In this article, we try to summarize the biology of HP-induced gastric cancer and discuss the current pharmacological approach to treat and prevent its carcinogenicity. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
23. EBV Associated Breast Cancer Whole Methylome Analysis Reveals Viral and Developmental Enriched Pathways.
- Author
-
Abdallah, Mohammad O. E., Algizouli, Ubai K., Suliman, Maram A., Abdulrahman, Rawya A., Koko, Mahmoud, Fessahaye, Ghimja, Shakir, Jamal H., Fahal, Ahmed H., Elhassan, Ahmed M., Ibrahim, Muntaser E., and Mohamed, Hiba S.
- Subjects
EPSTEIN-Barr virus ,BREAST cancer ,DNA methylation - Abstract
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 pilot 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 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 uncoveredmany clues to a possible role for EBV infection in BC. Conclusion: Our results clearly show the utility of epigenetic assays in interrogating breast cancer tumorigenesis, and pinpointing specific developmental and viral pathways dysregulation that might serve as potential biomarkers or targets for therapeutic interventions. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
24. Association of Epstein - Barr virus and breast cancer in Eritrea.
- Author
-
Fessahaye, Ghimja, Elhassan, Ahmed M., Elamin, Elwaleed M., Adam, Ameera A. M., Ghebremedhin, Anghesom, and Ibrahim, Muntaser E.
- Subjects
BREAST tumors ,DNA ,EPSTEIN-Barr virus diseases ,GENE expression ,GENOMES ,IMMUNOHISTOCHEMISTRY ,IN situ hybridization ,MEMBRANE proteins ,POLYMERASE chain reaction ,RNA ,DISEASE prevalence - Abstract
Background: The oncogenic potential of Epstein-Barr virus (EBV) in breast cancer is being increasingly recognized. Despite some controversies regarding such role, new evidence is suggesting a culpability of EBV in breast cancer, particularly in Africa where the virus has been originally associated with causation of several solid and hematological malignancies. One example is a report from Sudan implicating EBV as a prime etiologic agent for an aggressive type of breast cancer, where nearly 100% of tumor tissues were shown to carry viral signatures. To get a broader view on such association, other nearby countries should be investigated. The present study aims to determine the prevalence and possible associations of the virus in Eritrean breast cancer patients. Methods: Detection of EBV genome using primers that target Epstein Barr Encoded RNA (EBER) gene and Latent Membrane Protein-1 (LMP-1) gene sequences was performed by polymerase chain reaction (PCR) on DNA samples extracted from 144 formalin fixed paraffin embedded breast cancer tissues and 63 non-cancerous breast tissue as control group. A subset of PCR positive samples was evaluated for EBER gene expression by in situ hybridization (ISH). Expression of Latent Membrane Protein-2a (LMP2a) was also assessed by immunohistochemistry in a subset of 45 samples. Results: Based on PCR results, EBV genome signals were detected in a total of 40 samples (27.77%) as compared to controls (p-value = 0. 0031) with a higher sensitivity when using the EBER primers. Five out of the 14 samples stained by EBER-ISH 35.71% were positive for the virus indicating the presence of the viral genome within the tumor cells. Of those stained for IHC 7 (15.55%) were positive for LMP2a showing low viral protein frequency. Conclusions: Based on these findings it can be concluded that EBV in Eritrea is associated with a smaller subset of tumors, unlike neighboring Sudan, thus pointing to possible differences in population predisposition and diseases epidemiology. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
25. Candidate gene analysis supports a role for polymorphisms at TCF7L2 as risk factors for type 2 diabetes in Sudan.
- Author
-
Ibrahim, Amir T., Salih, Mohamed A. M., Hussain, Ayman, Ibrahim, Muntaser E., Mohamed, Hiba S., Ibrahim, Omima Abdeen, Jamieson, Sarra E., and Blackwell, Jenefer M.
- Subjects
TYPE 2 diabetes risk factors ,GENETIC polymorphism research ,SUDANESE ,DISEASES - Abstract
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, Pad
j:age/sex/BMI = 0.005). The strongest haplotype association (odds ratio 2.24; Padj: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, Padj:age/sex/BMI = 0.042) and rs1111876 at HHEX (odds ratio 0.60, 95 % confidence interval 0.39-0.93, Padj:age/sex/BMI = 0.022). Conclusions: Multiethnic associations between T2D and SNPs at TCF7L2, CAPN10 and HHEX extend to Sub-Saharan Africa, specifically Sudan. [ABSTRACT FROM AUTHOR]- Published
- 2016
- Full Text
- View/download PDF
26. Exome sequencing of a colorectal cancer family reveals shared mutation pattern and predisposition circuitry along tumor pathways.
- Author
-
Suleiman, Suleiman H., Koko, Mahmoud E., Nasir, Wafaa H., Elfateh, Ommnyiah, Elgizouli, Ubai K., Abdallah, Mohammed O. E., Alfarouk, Khalid O., Hussain, Ayman, Faisal, Shima, Ibrahim, Fathelrahamn M. A., Romano, Maurizio, Sultan, Ali, Banks, Lawrence, Newport, Melanie, Baralle, Francesco, Elhassan, Ahmed M., Mohamed, Hiba S., Ibrahim, Muntaser E., Wong, Christopher, and Xiaogang Wu
- Subjects
GENETICS of colon cancer ,NUCLEOTIDE sequencing ,GENETIC mutation - Abstract
The molecular basis of cancer and cancer multiple phenotypes are not yet fully understood. Next Generation Sequencing promises new insight into the role of genetic interactions in shaping the complexity of cancer. Aiming to outline the differences in mutation patterns between familial colorectal cancer cases and controls we analyzed whole exomes of cancer tissues and control samples from an extended colorectal cancer pedigree, providing one of the first data sets of exome sequencing of cancer in an African population against a background of large effective size typically with excess of variants. Tumors showed hMSH2 loss of function SNV consistent with Lynch syndrome. Sets of genes harboring insertions-deletions in tumor tissues revealed, however, significant GO enrichment, a feature that was not seen in control samples, suggesting that ordered insertions-deletions are central to tumorigenesis in this type of cancer. Network analysis identified multiple hub genes of centrality. ELAVL1/HuR showed remarkable centrality, interacting specially with genes harboring non-synonymous SNVs thus reinforcing the proposition of targeted mutagenesis in cancer pathways. A likely explanation to such mutation pattern is DNA/RNA editing, suggested here by nucleotide transition-to-transversion ratio that significantly departed from expected values (p-value 5e-6). NFKB1 also showed significant centrality along with ELAVL1, raising the suspicion of viral etiology given the known interaction between oncogenic viruses and these proteins. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
27. Resistance to cancer chemotherapy: failure in drug response from ADME to P-gp.
- Author
-
Alfarouk, Khalid O., Stock, Christian-Martin, Taylor, Sophie, Walsh, Megan, Muddathir, Abdel Khalig, Verduzco, Daniel, Bashir, Adil H. H., Mohammed, Osama Y., Elhassan, Gamal O., Harguindey, Salvador, Reshkin, Stephan J., Ibrahim, Muntaser E., and Rauch, Cyril
- Subjects
CHEMOTHERAPY complications ,DRUG resistance ,ABSORPTION (Physiology) ,METABOLISM ,EXCRETION - Abstract
Cancer chemotherapy resistance (MDR) is the innate and/or acquired ability of cancer cells to evade the effects of chemotherapeutics and is one of the most pressing major dilemmas in cancer therapy. Chemotherapy resistance can arise due to several host or tumor-related factors. However, most current research is focused on tumor-specific factors and specifically genes that handle expression of pumps that efflux accumulated drugs inside malignantly transformed types of cells. In this work, we suggest a wider and alternative perspective that sets the stage for a future platform in modifying drug resistance with respect to the treatment of cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
28. Part I: cancer in Sudan-burden, distribution, and trends breast, gynecological, and prostate cancers.
- Author
-
Elamin, Amany, Ibrahim, Muntaser E., Abuidris, Dafalla, Mohamed, Kamal Eldin H., and Mohammed, Sulma Ibrahim
- Subjects
- *
PROSTATE cancer , *BREAST cancer , *ONCOLOGY , *CANCER - Abstract
Despite the growing burden of cancer worldwide, it continues to receive low priority in Africa, across the continent and specifically in Sudan. This is due to political unrest, limited health resources, and other pressing public health issues such as infectious diseases. Lack of awareness about the magnitude of the current and future cancer burden among policy makers play a major role as well. Although, the real scope of cancer in Sudan is not known, the reported cases have increased from 303 in 1967-6303 in 2010. According to Globocan estimates, the top most common cancers in both sexes are breast, non-Hodgkin lymphoma, leukemia, esophagus, and colorectum. This review is the first of four papers that focuses on cancer, its distribution and trend as well as the risk factors most common in Sudan. It is expected that cancer will increase in Sudan as a result of migration of people from rural areas to urban cities in the pursuit of a better standard of living, which has resulted in lifestyle and behavioral changes that include tobacco chewing and smoking, unhealthy dieting, and a lack of physical activity. These changes are further exacerbated by the aging population and have made the country vulnerable to many diseases including cancer. These reviews are meant to provide a better understanding and knowledge required to plan appropriate cancer-control and prevention strategies in the country. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
29. Y-chromosome E haplogroups: their distribution and implication to the origin of Afro-Asiatic languages and pastoralism.
- Author
-
Gebremeskel, Eyoab I and Ibrahim, Muntaser E
- Subjects
- *
Y chromosome , *AFRASANS (African people) , *X chromosome , *SEX chromosomes , *PASTORAL societies , *AFROASIATIC languages - Abstract
Archeological and paleontological evidences point to East Africa as the likely area of early evolution of modern humans. Genetic studies also indicate that populations from the region often contain, but not exclusively, representatives of the more basal clades of mitochondrial and Y-chromosome phylogenies. Most Y-chromosome haplogroup diversity in Africa, however, is present within macrohaplogroup E that seem to have appeared 21 000-32 000 YBP somewhere between the Red Sea and Lake Chad. The combined analysis of 17 bi-allelic markers in 1214 Y chromosomes together with cultural background of 49 populations displayed in various metrics: network, multidimensional scaling, principal component analysis and neighbor-joining plots, indicate a major contribution of East African populations to the foundation of the macrohaplogroup, suggesting a diversification that predates the appearance of some cultural traits and the subsequent expansion that is more associated with the cultural and linguistic diversity witnessed today. The proto-Afro-Asiatic group carrying the E-P2 mutation may have appeared at this point in time and subsequently gave rise to the different major population groups including current speakers of the Afro-Asiatic languages and pastoralist populations. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
30. The Episode of Genetic Drift Defining the Migration of Humans out of Africa Is Derived from a Large East African Population Size.
- Author
-
Elhassan, Nuha, Gebremeskel, Eyoab Iyasu, Elnour, Mohamed Ali, Isabirye, Dan, Okello, John, Hussien, Ayman, Kwiatksowski, Dominic, Hirbo, Jibril, Tishkoff, Sara, and Ibrahim, Muntaser E.
- Subjects
GENETIC drift ,CYTOCHROME oxidase ,POPULATION biology ,MICROSATELLITE repeats ,COMPARATIVE studies ,BIOLOGICAL evolution - Abstract
Human genetic variation particularly in Africa is still poorly understood. This is despite a consensus on the large African effective population size compared to populations from other continents. Based on sequencing of the mitochondrial Cytochrome C Oxidase subunit II (MT-CO2), and genome wide microsatellite data we observe evidence suggesting the effective size (Ne) of humans to be larger than the current estimates, with a foci of increased genetic diversity in east Africa, and a population size of east Africans being at least 2-6 fold larger than other populations. Both phylogenetic and network analysis indicate that east Africans possess more ancestral lineages in comparison to various continental populations placing them at the root of the human evolutionary tree. Our results also affirm east Africa as the likely spot from which migration towards Asia has taken place. The study reflects the spectacular level of sequence variation within east Africans in comparison to the global sample, and appeals for further studies that may contribute towards filling the existing gaps in the database. The implication of these data to current genomic research, as well as the need to carry out defined studies of human genetic variation that includes more African populations; particularly east Africans is paramount. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
31. Vascular measurements correlate with estrogen receptor status.
- Author
-
Lloyd, Mark C., Alfarouk, Khalid O., Verduzco, Daniel, Bui, Marilyn M., Gillies, Robert J., Ibrahim, Muntaser E., Brown, Joel S., and Gatenby, Robert A.
- Subjects
ESTROGEN receptors ,IMMUNOHISTOCHEMISTRY ,GENETIC mutation ,BLOOD flow ,ANALYSIS of variance ,BREAST cancer treatment ,BLOOD vessels - Abstract
Background Breast carcinoma can be classified as either Estrogen Receptor (ER) positive or negative by immunohistochemical phenotyping, although ER expression may vary from 1 to 100% of malignant cells within an ER + tumor. This is similar to genetic variability observed in other tumor types and is generally viewed as a consequence of intratumoral evolution driven by random genetic mutations. Here we view cellular evolution within tumors as a classical Darwinian system in which variations in molecular properties represent predictable adaptations to spatially heterogeneous environmental selection forces. We hypothesize that ER expression is a successful adaptive strategy only if estrogen is present in the microenvironment. Since the dominant source of estrogen is blood flow, we hypothesized that, in general, intratumoral regions with higher blood flow would contain larger numbers of ER + cells when compared to areas of low blood flow and in turn necrosis. Methods This study used digital pathology whole slide image acquisition and advanced image analysis algorithms. We examined the spatial distribution of ER + and ER- cells, vascular density, vessel area, and tissue necrosis within histological sections of 24 breast cancer specimens. These data were correlated with the patients ER status and molecular pathology report findings. Results ANOVA analyses revealed a strong correlation between vascular area and ER expression and between high fractional necrosis and absent ER expression (R² = 39%; p < 0.003 and R² = 46%; p < 0.001), respectively). ER expression did not correlate with tumor grade or size. Conclusion We conclude that ER expression can be understood as a Darwinian process and linked to variations in estrogen delivery by temporal and spatial heterogeneity in blood flow. This correlation suggests strategies to promote intratumoral blood flow or a cyclic introduction of estrogen in the treatment schedule could be explored as a counter-intuitive approach to increase the efficacy of anti-estrogen drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
32. Epstein Barr virus: a prime candidate of breast cancer aetiology in Sudanese patients.
- Author
-
Yahia, Zeinab A., Adam, Ameera A. M., Elgizouli, Magdeldin, Hussein, Ayman, Masri, Mai A., Kamal, Mayada, Mohamed, Hiba S., Alzaki, Kamal, Elhassan, Ahmed M., Hamad, Kamal, and Ibrahim, Muntaser E.
- Subjects
BREAST tumors ,DNA ,EPSTEIN-Barr virus diseases ,METHYLATION ,POLYMERASE chain reaction ,RESEARCH funding - Abstract
Breast cancer is the commonest cancer in Sudanese women. Reported genetic alterations in the form of mutations in tumor suppressors are low in frequencies and could not explain the peculiarities of the diseases including its focal nature. Potential contributors disease aetiology include oncogenic viruses such as Epstein-Barr virus (EBV), an established culprit of nasopharyngeal carcinoma, one of the most frequent cancers in Sudan. In this study, DNA was extracted from malignant tissue samples and healthy tumour-free tissue from the same breast. Polymerase chain Reaction (PCR) was used to amplify two genes encoding for EBV viral proteins. The presence of Epstein-Barr virus and its cellular localization was confirmed by in situ hybridization (ISH) for Epstein-Barr encoded small RNAs (EBERs). Given the reported low frequency of mutations in BRCA1 and BRCA2 in Sudanese breast cancer patients, the methylation status of six tumor suppressor genes was investigated using methylation specific PCR. EBV genome was detected in 55.5% (n = 90) of breast cancer tissues as compared to 23% in control tissue samples (p = 0.0001). Using ISH, EBV signal was detected in all 18 breast cancer biopsies examined while all five normal breast tissue biopsies tested were negative for EBV. Of six tumour suppressor genes investigated BRCA1, BRCA2, and p14 appeared to be under strong epigenetic silencing. In conclusion, we present evidence of a strong association between EBV and breast carcinoma in Sudanese patients, and considerable epigenetic silencing of tumor suppressors that may likely be an outcome or an association with viral oncogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
33. Distribution of erythrocyte binding antigen 175 (EBA-175) gene dimorphic alleles in Plasmodium falciparum field isolates from Sudan.
- Author
-
Adam, Ahmed A. M., Amine, Ahmed A. A., Hassan, Dina A., Omer, Waleed H., Nour, Bakri Y., Zechariah Jebakumar, Arulanantham, Ibrahim, Muntaser E., Abdulhadi, Nasreldin H., and Mohamed, Hiba S.
- Subjects
ERYTHROCYTES ,ANTIGENS ,ALLELES ,PLASMODIUM falciparum ,GLYCOPHORIN ,DIMORPHISM (Biology) ,PHYSIOLOGY - Abstract
Background The Erythrocyte Binding Antigen (EBA) 175 has been considered as one of the most important Plasmodium falciparum (P. falciparum) merozoite ligands that mediate invasion of the erythrocytes through their sialated receptor: Glycophorin A (GPA). The effect of the EBA 175 dimorphic alleles (F and C) on the severity of the disease is not yet fully understood. Therefore this study was designed to assess the distribution of the divergent dimorphic alleles of P. falciparum EBA-175 (F and C) in three different geographical areas in Sudan and the possible association of this dimorphism with the severity of the disease. Methods A sum of 339 field isolates of P. falciparum obtained from patients in three different geographical areas in Sudan were screened for the dimorphic alleles (F, C) of the EBA-175 using nested PCR. Results The percentage of F, C, and mixed F/C alleles were; 41%, 51%, and 8% respectively. F and C alleles showed significantly different distributions in the various geographic areas (p = 0.00). There was no significant association between malaria clinical manifestation and P. falciparum EBA-175 F and C alleles frequencies Conclusions This study showed a significant differential distribution of F and C alleles in different geographical malaria endemic areas. No significant association was observed between F and C alleles and different malaria phenotypes. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
34. Riparian ecosystems in human cancers.
- Author
-
Alfarouk, Khalid O., Ibrahim, Muntaser E., Gatenby, Robert A., and Brown, Joel S.
- Subjects
- *
RIPARIAN ecology , *ECOSYSTEMS , *GENETIC mutation , *BIODIVERSITY , *RIPARIAN areas , *METABOLITES - Abstract
Intratumoral evolution produces extensive genetic heterogeneity in clinical cancers. This is generally attributed to an increased mutation rate that continually produces new genetically defined clonal lineages. Equally important are the interactions between the heritable traits of cancer cells and their microenvironment that produces natural selection favoring some clonal 'species' over others. That is, while mutations produce the heritable variation, environmental selection and cellular adaptation govern the strategies (and genotypes) that can proliferate within the tumor ecosystem. Here we ask: What are the dominant evolutionary forces in the cancer ecosystem? We propose that the tumor vascular network is a common and primary cause of intratumoral heterogeneity. Specifically, variations in blood flow result in variability in substrate, such as oxygen, and metabolites, such as acid, that serve as critical, but predictable, environmental selection forces. We examine the evolutionary and ecological consequences of variable blood flow by drawing an analogy to riparian habitats within desert landscapes. We propose that the phenotypic properties of cancer cells will exhibit predictable spatial variation within tumor phenotypes as a result of proximity to blood flow. Just as rivers in the desert create an abrupt shift from the lush, mesic riparian vegetation along the banks to sparser, xeric and dry-adapted plant species in the adjacent drylands, we expect blood vessels within tumors to promote similarly distinct communities of cancer cells that change abruptly with distance from the blood vessel. We propose vascular density and blood flow within a tumor as a primary evolutionary force governing variations in the phenotypic properties of cancer cells thus providing a unifying ecological framework for understanding intratumoral heterogeneity. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
35. The emergence of Y-chromosome haplogroup J1e among Arabic-speaking populations.
- Author
-
Chiaroni, Jacques, King, Roy J., Myres, Natalie M., Henn, Brenna M., Ducourneau, Axel, Mitchell, Michael J., Boetsch, Gilles, Sheikha, Issa, Lin, Alice A., Nik-Ahd, Mahnoosh, Ahmad, Jabeen, Lattanzi, Francesca, Herrera, Rene J., Ibrahim, Muntaser E., Brody, Aaron, Semino, Ornella, Kivisild, Toomas, and Underhill, Peter A.
- Subjects
Y chromosome ,CELL nuclei ,KARYOKINESIS ,GENETICS ,CELL division - Abstract
Haplogroup J1 is a prevalent Y-chromosome lineage within the Near East. We report the frequency and YSTR diversity data for its major sub-clade (J1e). The overall expansion time estimated from 453 chromosomes is 10 000 years. Moreover, the previously described J1 (DYS388=13) chromosomes, frequently found in the Caucasus and eastern Anatolian populations, were ancestral to J1e and displayed an expansion time of 9000 years. For J1e, the Zagros/Taurus mountain region displays the highest haplotype diversity, although the J1e frequency increases toward the peripheral Arabian Peninsula. The southerly pattern of decreasing expansion time estimates is consistent with the serial drift and founder effect processes. The first such migration is predicted to have occurred at the onset of the Neolithic, and accordingly J1e parallels the establishment of rain-fed agriculture and semi-nomadic herders throughout the Fertile Crescent. Subsequently, J1e lineages might have been involved in episodes of the expansion of pastoralists into arid habitats coinciding with the spread of Arabic and other Semitic-speaking populations. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
36. Candidate malaria susceptibility/protective SNPs in hospital and population-based studies: the effect of sub-structuring.
- Author
-
Eid, Nahid A., Hussein, Aymen A., Elzein, Abier M., Mohamed, Hiba S., Rockett, Kirk A., Kwiatkowski, Dominic P., and Ibrahim, Muntaser E.
- Subjects
MALARIA ,GENETICS of bacterial diversity ,DNA - Abstract
Background: Populations of East Africa including Sudan, exhibit some of the highest indices of genetic diversity in the continent and worldwide. The current study aims to address the possible impact of population structure and population stratification on the outcome of case-control association-analysis of malaria candidate-genes in different Sudanese populations, where the pronounced genetic heterogeneity becomes a source of concern for the potential effect on the studies outcome. Methods: A total of 72 SNPs were genotyped using the Sequenom® iPLEX Gold assay in 449 DNA samples that included; cases and controls from two village populations, malaria patients and out-patients from the area of Sinnar and additional controls consisting of healthy Nilo-Saharan speaking individuals. The population substructure was estimated using the Structure 2.2 programme. Results & Discussion: The Hardy-Weinberg Equilibrium values were generally within expectation in Hausa and Massalit. However, in the Sinnar area there was a notable excess of homozygosity, which was attributed to the Whalund effect arising from population amalgamation within the sample. The programme STRUCTURE revealed a division of both Hausa and Massalit into two substructures with the partition in Hausa more pronounced than in Massalit; In Sinnar there was no defined substructure. More than 25 of the 72 SNPs assayed were informative in all areas. Some important SNPs were not differentially distributed between malaria cases and controls, including SNPs in CD36 and NOS2. A number of SNPs showed significant p-values for differences in distribution of genotypes between cases and controls including: rs1805015 (in IL4R1) (P = 0.001), rs17047661 (in CR1) (P = 0.02) and rs1800750 (TNF-376)(P = 0.01) in the hospital samples; rs1050828 (G6PD+202) (P = 0.02) and rs1800896 (IL10-1082) (P = 0.04) in Massalit and rs2243250 (IL4-589) (P = 0.04) in Hausa. Conclusions: The difference in population structure partly accounts for some of these significant associations, and the strength of association proved to be sensitive to all levels of sub-structuring whether in the hospital or populationbased study. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
37. Loss of balancing selection in the βS globin locus.
- Author
-
Salih, Niven A, Hussain, Ayman A, Almugtaba, Ibrahim A, Elzein, Abeir M, Elhassan, Ibrahim M, Khalil, Eltahir AG, Ishag, Hani B, Mohammed, Hiba S, Kwiatkowski, Dominic, and Ibrahim, Muntaser E
- Subjects
MALARIA ,GLOBIN genes ,INFECTIOUS disease transmission ,GENETIC polymorphisms ,MEDICAL genetics - Abstract
Background: 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. Methods: 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 future generations. Results: Genotype frequencies were within Hardy-Weinberg expectations in Hausa and Massalit in the total sample set but not within the different age groups. There was a trend for a decrease of the HbS allele frequency in Hausa and an increase of frequency in Massalit. Although the HbS allele was able to confer significant protection from the clinical episodes of malaria in the two populations, as suggested by the odds ratios, the overall relative fitness of the HbS allele seems to have declined in Hausa. Conclusions: Such loss of balancing selection could be due to a combined effect of preponderance of non-clinical malaria in Hausa, and the deleterious effect of the homozygous HbS under circumstances of endogamy. [ABSTRACT FROM AUTHOR]
- Published
- 2010
- Full Text
- View/download PDF
38. Genetic studies of African populations: an overview on disease susceptibility and response to vaccines and therapeutics.
- Author
-
Sirugo, Giorgio, Hennig, Branwen J., Adeyemo, Adebowale A., Matimba, Alice, Newport, Melanie J., Ibrahim, Muntaser E., Ryckman, Kelli K., Tacconelli, Alessandra, Mariani-Costantini, Renato, Novelli, Giuseppe, Soodyall, Himla, Rotimi, Charles N., Ramesar, Raj S., Tishkoff, Sarah A., and Williams, Scott M.
- Subjects
HUMAN genetic variation ,VACCINES ,MALARIA ,TUBERCULOSIS ,SCHISTOSOMIASIS ,COMMUNICABLE diseases - Abstract
Africa is the ultimate source of modern humans and as such harbors more genetic variation than any other continent. For this reason, studies of the patterns of genetic variation in African populations are crucial to understanding how genes affect phenotypic variation, including disease predisposition. In addition, the patterns of extant genetic variation in Africa are important for understanding how genetic variation affects infectious diseases that are a major problem in Africa, such as malaria, tuberculosis, schistosomiasis, and HIV/AIDS. Therefore, elucidating the role that genetic susceptibility to infectious diseases plays is critical to improving the health of people in Africa. It is also of note that recent and ongoing social and cultural changes in sub-Saharan Africa have increased the prevalence of non-communicable diseases that will also require genetic analyses to improve disease prevention and treatment. In this review we give special attention to many of the past and ongoing studies, emphasizing those in Sub-Saharan Africans that address the role of genetic variation in human disease. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
39. Y Chromosome Lineage- and Village-Specific Genes on Chromosomes 1p22 and 6q27 Control Visceral Leishmaniasis in Sudan.
- Author
-
Miller, E. Nancy, Fadl, Manal, Mohamed, Hiba S., Elzein, Abier, Jamieson, Sarra E., Cordell, Heather J., Peacock, Christopher S., Fakiola, Michaela, Raju, Madhuri, Khalil, Eltahir A., Elhassan, Ahmed, Musa, Ahmed M., Ibrahim, Muntaser E., and Blackwell, Jenefer M.
- Subjects
LEISHMANIASIS ,GENOMES ,GENE mapping ,Y chromosome ,GENES ,SEX chromosomes - Abstract
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 = 1.72 x 10
-7 ; empirical p < 1 x 10-5 ; λs = 5.1) and 6q27 (LOD score 3.74; nominal p = 1.68 x 10-5 ; empirical p < 1 x 10-4 ; λs = 2.3) that were Y chromosome-lineage 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. [ABSTRACT FROM AUTHOR]- Published
- 2007
- Full Text
- View/download PDF
40. Evolutionary conservation of RNA editing in the genus Leishmania
- Author
-
Ibrahim, Muntaser E., Mahdi, Muzamil A., Bereir, Rihab E., Giha, Rania S., and Wasunna, Christina
- Subjects
- *
RNA editing , *GENETICS , *URIDINE , *CYTOCHROME oxidase , *METALLOENZYMES - Abstract
Abstract: RNA editing in kinetoplastids is the process by which vital genetic informations are restored through insertion and deletion of uridine residues in coding sequences, particularly those of the mitochondrial pre-mRNA. Mammalian infecting Leishmania were not analyzed before for the presence of RNA editing to establish whether the mechanism is still in use in higher lineages of the genus. The Cytochrome Oxidase gene of Leishmania tarentolae is known to be edited at its 3′ end with gRNA encoded in the region immediately downstream. We sequenced DNA and cDNA of the COII gene of Leishmania donovani and compared those to Leishmania tarentolae sequences from the database. The results reveal an insertion of uridines in a manner identical to L. tarentolae, leading to restoration of the amino acid sequence with relative conservation of the gRNA region. We conclude that RNA editing as a posttranscriptional mechanism is still conserved within higher evolutionary lineages of the genus Leishmania. [Copyright &y& Elsevier]
- Published
- 2008
- Full Text
- View/download PDF
41. Co-introgression of Y-chromosome haplogroups and the sickle cell gene across Africa's Sahel.
- Author
-
Bereir, Rihab E., Hassan, Hisham Y., Salih, Niven A., Underhill, Peter A., Cavalli-Sforza, Luigi L., Hussain, Ayman A., Kwiatkowski, Dominic, and Ibrahim, Muntaser E.
- Subjects
Y chromosome ,EMIGRATION & immigration ,GENETIC markers ,GENETIC polymorphisms ,HUMAN genetics - Abstract
The Sahel that extends from the Atlantic Ocean to the Ethiopian highland is a historical reservoir of Africa's cultures and grandest populations and a known arena of ancient and recent migrations. We are interested in the issue whether such migrations were also carriers of genetic traits and whether this introgression could be associated with population genetic markers. Based on analysis of Y-chromosome haplogroups, we present evidence that the sickle gene, one of the major protective polymorphisms known in malaria, has in fact found its way only recently to the gene pool of the populations in eastern Sahel. We discuss the possible dynamics of the process and give estimates of the age of the introduction of the S allele into eastern Sahel.European Journal of Human Genetics (2007) 15, 1183–1185; doi:10.1038/sj.ejhg.5201892; published online 15 August 2007 [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
42. The Pentose Phosphate Pathway Dynamics in Cancer and Its Dependency on Intracellular pH.
- Author
-
Alfarouk, Khalid O., Ahmed, Samrein B. M., Elliott, Robert L., Benoit, Amanda, Alqahtani, Saad S., Ibrahim, Muntaser E., Bashir, Adil H. H., Alhoufie, Sari T. S., Elhassan, Gamal O., Wales, Christian C., Schwartz, Laurent H., Ali, Heyam S., Ahmed, Ahmed, Forde, Patrick F., Devesa, Jesus, Cardone, Rosa A., Fais, Stefano, Harguindey, Salvador, and Reshkin, Stephan J.
- Subjects
PENTOSE phosphate pathway ,NICOTINAMIDE adenine dinucleotide phosphate ,GLYCOLYSIS ,NUCLEIC acids - Abstract
The Pentose Phosphate Pathway (PPP) is one of the key metabolic pathways occurring in living cells to produce energy and maintain cellular homeostasis. Cancer cells have higher cytoplasmic utilization of glucose (glycolysis), even in the presence of oxygen; this is known as the "Warburg Effect". However, cytoplasmic glucose utilization can also occur in cancer through the PPP. This pathway contributes to cancer cells by operating in many different ways: (i) as a defense mechanism via the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) to prevent apoptosis, (ii) as a provision for the maintenance of energy by intermediate glycolysis, (iii) by increasing genomic material to the cellular pool of nucleic acid bases, (iv) by promoting survival through increasing glycolysis, and so increasing acid production, and (v) by inducing cellular proliferation by the synthesis of nucleic acid, fatty acid, and amino acid. Each step of the PPP can be upregulated in some types of cancer but not in others. An interesting aspect of this metabolic pathway is the shared regulation of the glycolytic and PPP pathways by intracellular pH (pHi). Indeed, as with glycolysis, the optimum activity of the enzymes driving the PPP occurs at an alkaline pHi, which is compatible with the cytoplasmic pH of cancer cells. Here, we outline each step of the PPP and discuss its possible correlation with cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
43. The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer.
- Author
-
Alfarouk, Khalid O., Ahmed, Samrein B. M., Ahmed, Ahmed, Elliott, Robert L., Ibrahim, Muntaser E., Ali, Heyam S., Wales, Christian C., Nourwali, Ibrahim, Aljarbou, Ahmed N., Bashir, Adil H. H., Alhoufie, Sari T. S., Alqahtani, Saad Saeed, Cardone, Rosa A., Fais, Stefano, Harguindey, Salvador, and Reshkin, Stephan J.
- Subjects
CELL proliferation ,ACIDOSIS ,PHYSIOLOGICAL adaptation ,CANCER invasiveness ,CELL lines ,EXTRACELLULAR space ,GLYCOLYSIS ,GROWTH factors ,HYDROGEN-ion concentration ,METASTASIS ,MITOCHONDRIA ,OXIDATION-reduction reaction ,PHOSPHORYLATION ,TUMORS ,WATER-electrolyte imbalances ,OXIDATIVE stress ,DISEASE progression ,NEOPLASTIC cell transformation - Abstract
Cancer cells and tissues have an aberrant regulation of hydrogen ion dynamics driven by a combination of poor vascular perfusion, regional hypoxia, and increased the flux of carbons through fermentative glycolysis. This leads to extracellular acidosis and intracellular alkalinization. Dysregulated pH dynamics influence cancer cell biology, from cell transformation and tumorigenesis to proliferation, local growth, invasion, and metastasis. Moreover, this dysregulated intracellular pH (pHi) drives a metabolic shift to increased aerobic glycolysis and reduced mitochondrial oxidative phosphorylation, referred to as the Warburg effect, or Warburg metabolism, which is a selective feature of cancer. This metabolic reprogramming confers a thermodynamic advantage on cancer cells and tissues by protecting them against oxidative stress, enhancing their resistance to hypoxia, and allowing a rapid conversion of nutrients into biomass to enable cell proliferation. Indeed, most cancers have increased glucose uptake and lactic acid production. Furthermore, cancer cells have very dysregulated electrolyte balances, and in the interaction of the pH dynamics with electrolyte, dynamics is less well known. In this review, we highlight the interconnected roles of dysregulated pH dynamics and electrolytes imbalance in cancer initiation, progression, adaptation, and in determining the programming and reprogramming of tumor cell metabolism. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
44. Distribution of Duffy Phenotypes among Plasmodium vivax Infections in Sudan.
- Author
-
Albsheer, Musab M.A., Pestana, Kareen, Ahmed, Safaa, Elfaki, Mohammed, Gamil, Eiman, Ahmed, Salma M., Ibrahim, Muntaser E., Musa, Ahmed M., Lo, Eugenia, and Hamid, Muzamil M. Abdel
- Subjects
PLASMODIUM vivax ,ATLANTIC cod ,ERYTHROCYTES ,BLOOD groups ,PHENOTYPES ,INFECTION - Abstract
Negative Duffy expression on the surface of human red blood cells was believed to be a barrier for Plasmodium vivax infection in most Africans. However, P. vivax has been demonstrated to infect Duffy-negative individuals in several Central and East African countries. In this study, we investigated the distribution of Duffy blood group phenotypes with regard to P. vivax infection and parasitemia in Sudan. Out of 992 microscopic-positive malaria samples, 190 were identified as P. vivax positive infections. Among them, 186 were P. vivax mono-infections and 4 were mixed P. vivax and Plasmodium falciparum infections. A subset of 77 samples was estimated with parasitemia by quantitative real-time PCR. Duffy codons were sequenced from the 190 P. vivax positive samples. We found that the Duffy Fy(a-b+) phenotype was the most prevalent, accounting for 67.9% of all P. vivax infections, while homozygous Duffy-negative Fy(a-b-) accounted for 17.9% of the P. vivax infections. The prevalence of infection in Fy(a-b+) and Fy(a+b-)were significantly higher than Fy(a-b-) phenotypes (p = 0.01 and p < 0.01, respectively). A significantly low proportion of P. vivax infection was observed in Duffy negative individuals Fy(a-b-). This study highlights the prevalence of P. vivax in Duffy-negatives in Sudan and indicates low parasitemia among the Duffy-negative individuals. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
45. Case report of a novel homozygous splice site mutation in <italic>PLA2G6</italic> gene causing infantile neuroaxonal dystrophy in a Sudanese family.
- Author
-
Elsayed, Liena E. O., Mohammed, Inaam N., Hamed, Ahlam A. A., Elseed, Maha A., Salih, Mustafa A. M., Yahia, Ashraf, Siddig, Rayan A., Amin, Mutaz, Koko, Mahmoud, Elbashir, Mustafa I., Ibrahim, Muntaser E., Brice, Alexis, Ahmed, Ammar E., and Stevanin, Giovanni
- Subjects
GENETIC mutation ,DYSTROPHY ,PHENOTYPES - Abstract
Background: Infantile neuroaxonal dystrophy (INAD) is a rare hereditary neurological disorder caused by mutations in
PLA2G6 . The disease commonly affects children below 3 years of age and presents with delay in motor skills, optic atrophy and progressive spastic tetraparesis. Studies of INAD in Africa are extremely rare, and genetic studies from Sub Saharan Africa are almost non-existent. Case presentation: Two Sudanese siblings presented, at ages 18 and 24 months, with regression in both motor milestones and speech development and hyper-reflexia. Brain MRI showed bilateral and symmetrical T2/FLAIR hyperintense signal changes in periventricular areas and basal ganglia and mild cerebellar atrophy. Whole exome sequencing with confirmatory Sanger sequencing were performed for the two patients and healthy family members. A novel variant (NM_003560.2 c.1427 + 2 T > C) acting on a splice donor site and predicted to lead to skipping of exon 10 was found inPLA2G6 . It was found in a homozygous state in the two patients and homozygous reference or heterozygous in five healthy family members. Conclusion: This variant has one very strong (loss of function mutation) and three supporting evidences for its pathogenicity (segregation with the disease, multiple computational evidence and specific patients' phenotype). Therefore this variant can be currently annotated as "pathogenic". This is the first study to report mutations inPLA2G6 gene in patients from Sudan. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
46. Insights into the possible role of IFNG and IFNGR1 in Kala-azar and Post Kala-azar Dermal Leishmaniasis in Sudanese patients.
- Author
-
Salih, Mohamed A M, Fakiola, Michaela, Abdelraheem, Mohamed H, Younis, Brima M, Musa, Ahmed M, ElHassan, Ahmed M, Blackwell, Jenefer M, Ibrahim, Muntaser E, and Mohamed, Hiba S
- Abstract
Background: Little is known about the parasite/host factors that lead to Post Kala-azar Dermal Leishmaniasis (PKDL) in some visceral leishmaniasis (VL) patients after drug-cure. Studies in Sudan provide evidence for association between polymorphisms in the gene (IFNGR1) encoding the alpha chain of interferon-γ receptor type I and risk of PKDL. This study aimed to identify putative functional polymorphisms in the IFNGR1 gene, and to determine whether differences in expression of interferon-γ (IFNG) and IFNGR1 at the RNA level are associated with pathogenesis of VL and/or PKDL in Sudan.Methods: Sanger sequencing was used to re-sequence 841 bp of upstream, exon1 and intron1 of the IFNGR1 gene in DNA from 30 PKDL patients. LAGAN and SYNPLOT bioinformatics tools were used to compare human, chimpanzee and dog sequences to identify conserved noncoding sequences carrying putative regulatory elements. The relative expression of IFNG and IFNGR1 in paired pre- and post-treatment RNA samples from the lymph nodes of 24 VL patients, and in RNA samples from skin biopsies of 19 PKDL patients, was measured using real time PCR. Pre- versus post-treatment expression was evaluated statistically using the nonparametric Wilcoxon matched pairs signed-rank test.Results: Ten variants were identified in the 841 bp of sequence, four of which are novel polymorphisms at -77A/G, +10 C/T, +18C/T and +91G/T relative to the IFNGR1 initiation site. A cluster of conserved non-coding sequences with putative regulatory variants was identified in the distal promoter of IFNGR1. Variable expression of IFNG was detected in lymph node aspirates of VL patients before treatment, with a marked reduction (P = 0.006) in expression following treatment. IFNGR1 expression was also variable in lymph node aspirates from VL patients, with no significant reduction in expression with treatment. IFNG expression was undetectable in the skin biopsies of PKDL cases, while IFNGR1 expression was also uniformly low.Conclusions: Uniformly low expression of IFN and IFNGR1 in PKDL skin biopsies could explain parasite persistence and is consistent with prior demonstration of genetic association with IFNGR1 polymorphisms. Identification of novel potentially functional rare variants at IFNGR1 makes an important general contribution to knowledge of rare variants of potential relevance in this Sudanese population. [ABSTRACT FROM AUTHOR]- Published
- 2014
- Full Text
- View/download PDF
47. The epidemiology of visceral leishmaniasis in East Africa: hints and molecular revelations
- Author
-
Ibrahim, Muntaser E.
- Subjects
LEISHMANIASIS ,EPIDEMIOLOGY ,MOLECULAR biology - Abstract
Visceral leishmaniasis appears in the form of notoriously devastating epidemics and as an endemic disease of sporadic nature. In an attempt to understand the nature of this difference and its underlying causes, and to identify possible mechanisms for the instigation of outbreaks, the current status of the characterization of the parasite, its taxonomy, host immunity and genetics, are reviewed with the main focus on eastern Africa, one of the places where the dichotomous epidemiology of the disease is most pronounced. The new molecular tools offer various insights into the understanding of the complex epidemiology of visceral leishmaniasis and the interplay between parasite and host factors. Further insights are also provided on the parts played by demography, genetic history and geography in shaping the overall global portrait of the disease. [Copyright &y& Elsevier]
- Published
- 2004
48. Sudanese mucosal leishmaniasis: isolation of a parasite within the Leishmania donovani complex that differs genotypically from L. donovani causing classical visceral leishmaniasis
- Author
-
Mahdi, Muzamil, Elamin, Elwaleed M., Melville, Sara E., Musa, Ahmed M., Blackwell, Jenefer M., Mukhtar, Moawia M., Elhassan, Ahmed M., and Ibrahim, Muntaser E.
- Subjects
- *
LEISHMANIASIS , *PROTOZOAN diseases , *VISCERAL leishmaniasis , *PARASITES , *CYTOCHROME oxidase - Abstract
Mucosal leishmaniasis, which is a sporadic disease in the Sudan, was shown by isoenzyme characterization and PCR to be caused by Leishmania donovani. However, it was not clear if the parasite was exactly the same strain as that causing visceral leishmaniasis (VL), or of a different strain. We utilized a new generation of molecular DNA markers, minisatellites and kinetoplast DNA, for rapid characterization of the parasite. The results show that the genotypes of some of the parasites causing VL are different from those causing mucosal leishmaniasis. The L. donovani isolates causing visceral disease, as well as post-kala-azar mucosal leishmaniasis (PKML), have been shown to possess characteristic haplotypes. However, sequencing of a portion of the cytochrome oxidase II (COII) gene indicates that the parasite that invades the oral mucosa is divergent from other parasites causing VL. It appears to possess features of a more ancestral parasite with pronounced sequence homology to L. major. This agrees with earlier studies where isolates of mucosal leishmaniasis have been shown to possess an isoenzyme profile distinct from L. donovani and a different geographical distribution, albeit often overlapping with that of L. donovani. [Copyright &y& Elsevier]
- Published
- 2005
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.