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Types of chromosomal abnormalities

Frequency and the Types of chromosomal abnormalities in patients with Primary Amenorrhea in Sudan

Hiba Satti ,Imad Fadl-Elmula , Lamis Beshir , Abdelbagi Alzain

Study objective: to detect the frequency and the type of chromosomal abnormalities  in patients with primary Amenorrhea (PA)

Material and Methods:Chromosomal analysis  was carried out for  patients with primary amenorrhea who attended Elite genetics center or referred from other clinics in Khartoum, Sudan were retrospectively analyzed from 2017and 2018.

Results:The present study aimed at performing chromosomal analysis in patients presenting with primary amenorrhea (n=169) employing G banding. The karyotype results revealed that 50.3% (n=85) of the patients had normal karyotypes consistent with their female sex. 49.7% (n=84) showed abnormal karyotypes. Karyotype abnormalities were due to numerical aberration, structural abnormalities in the chromosomes or XY karyotypes inconsistent with the patients’ sex. 
Conclusion : Chromosomal abnormalities are common causes of primary amenorrhea in Sudanese patients. The results of the present study imply the inclusion of chromosomal analysis and genetic counseling for all patients with PA for early diagnosis. Of 169 cases with PA, 85 patients had normal karyotypes which suggest that other causes at gene level need to be further explored beside chromosomal abnormalities.
Keywords: 
primary amenorrhea(PA), chromosomal abnormalities, karyotyping, cytogenetic study,
turner syndrome, testicular feminization syndrome, triple X karyotype

 

 

 

 

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Malaria and Visceral Leishmaniasis

Overdominance Effects between Malaria and Visceral Leishmaniasis in the 5q31 Region

 

Abstract:

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

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Ancestral Genomes and the History of Adaptation

Ancestral Genomes and the History of Adaptation

Maha M Osman1, 2, Rayan S Ali1, Mahmoud Koko1, Muntaser E Ibrahim1*

1 Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.

2 Commission for Biotechnology and Genetic Engineering, National Center for Research, Sudan.

*Corresponding author: Prof. Muntaser E Ibrahim, mibrahim@iend.org

Abstract

The evolutionary history of a species is best seen from the summation of genetic variation across its genome. Genomes of African populations are believed to have retained some of the ancestral states of their genetic variation based on autosomes and sex specific chromosomes as well. In order to understand the evolutionary history of human populations in relation to other hominines, including the Neanderthal as a close species, and in attempt to gain insights to mechanisms of human adaptation, genomic data in different classes of adaptive traits were compared. Sudanese samples were sequenced on IlluminaHiSeq2000 platform. Sequences were compared to Neanderthal and global samples collected from 1000 Genomes and UCSC browsers.  Genes of adaptive traits and whole mitochondrial genomes and genes were extracted using Linux commands and Bioinformatics tools. Different software programs and statistical methods were used include; population differentiation test (FST), principal component analyses (PCA), Tajima Test for selective neutrality, phylogenetic trees were constructed using BEAST and MEGA7. Whole mitogenomes produced robust phylogenies that were greatly concordant with available HVRI, indicating that the HVRI has the upper hand in depicting the overall information content of the mtDNA sequence variation. Skyline plots based on HVRI show expansion dates to alter when the north eastern sequences are used compared to the plot of the world population, indicating the pivotal contribution of east Africans to human key evolutionary events. The results indicate that although Neanderthal and humans are adequately divergent in terms of speciation and genetic distance, ample variations are retained more pronouncedly in the biological class of variations.  Interestingly and as manifestation of the peculiarity of cultural variations to humans there was an observed divergence between humans and Neanderthal, manifested in reduced clustering and higher distance metrics, indicating the effect of cultural evolutionary forces.

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CONSANGUINEOUS MARRIAGE

KNOWLEDGE, ATTITUDE AND PRACTICE OF CONSANGUINEOUS MARRIAGE, IN SUDAN 2018.

Fatima A Elmugadam1, Liena ELsayed3, Haytham M Gorshi2, Almigdad HMohammed1, Murad Almak1, IsraaH Hussain1 Mohammed A.Farag1, Mohammed S.Tawar1, Elhami A Ahmed4, Almegdad S A1, Wadah O Awad1, Ahmed M Musa

Affiliation:

1- Khartoum University, Faculty of Medicine, Sudan

2- Institute of Endemic Diseases, Faculty of medicine, University of Khartoum, Sudan.

 3- Department of Biochemistry, Faculty of Medicine, University of Khartoum, Sudan.

4- UNESCO chair in Bioethics, Faculty of Medicine, University of Khartoum, Sudan.

Aim: The study aimed to assess the knowledge, attitude and practice aspects on the relationship of consanguinity to negative health outcomes. Also, to explore the attitude towards premarital genetic testing.

 

Background: Consanguinity (intra-familial marriage) is a global health problem with various adverse health outcomes. As this practice increases homozygosity of recessive alleles, it results in higher risk of early mortality and morbidity. Although, Sudan has one of the highest rates of consanguinity exceeding 40-50%.

Methodology: Data was collected from 1089 participants. Study was conducted in 13 urban and semi urban areas from 8 different states, using convenience sampling, trained interviewers paid house visits. Sudanese residents, 18 years and above, irrespective of their socio-economic status, were interviewed based on a locally generated and tested questionnaire. Analysis was done using descriptive and inferential statistics.

Results: 518 (48%) of participants were females, 571(52%) were males. about 800(73%) were among 18-40 years’ age group. The majority of respondents 437(39%) were college graduates. 803(74%) agreed on the negative health consequences of consanguinity, while 150(14%) opposed and 136 (12%) said “I do not know”. Among the respondents, 696(64%) showed non-preference for consanguineous marriage, Most frequently due to the possible transmission of genetic diseases. Of the 393 (36%) that showed preference the most frequent reason was its contribution to the stability of marriage.  When asked if they were willing to undergo premarital genetic testing, 908(83%) of respondents agreed to take it.

Conclusion: in our study, the overall awareness towards the issue was moderately high. But the practice still persists also in high rates.  It is not a revolution needed against consanguineous marriage in Sudan, rather, we need more investigation and integration of public health genomics sector to build efficient community-based awareness programs.

Keywords: Consanguinity; awareness; attitude; Sudan.

 

Presenter: Fatima Abdelhakam Abdellatif, MBBS, Faculty of Medicine University of Khartoum.

 

 

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Haplotype Diversity

Haplotype Diversity and Structure of Y Chromosome STR and SNPs of East Africans: further evidence to the antiquity of its populations

Abstract

East Africa has been in the spotlight of palaeoanthropological investigation for its role as a potential cradle of humanity and as a gateway out of Africa Since the discovery of the first hominin fossils. A Y chromosome SNP and mitochondrial genotyping on east African populations complement this notion and demonstrated the high effective population size and diversity of its populations attesting to the antiquity of the populations of the region. As Y chromosome STRs analysis has become increasingly important for forensic and human population genetics study; in this study Y-chromosome specific STRs (Y-STRs) and SNPs genotyping are used to study the recent population histories and their role in paternity testing and forensic applications in east African populations. To answer these pertinent questions a total of 562 unrelated male samples (94 from this study) from different east African populations were analysed for their 17- loci Y-STR distribution. Moreover, a Phylogenetic and population differentiation analysis of 17-loci Y-STR were carried out on the east African and global samples to see the contribution of east Africans to the global genetic landscape.

The 17 loci Y-STR loci analysis allowed a total of 451 (395 unique and 56 shared) haplotypes to be defined.  SNP defined haplogroups identified and subsequent phylogenetic and population differentiation analyses done in the studied populations once more attesting to the long existence of the east African populations and their contribution to the out-of-Africa scenario. Haplotypes differences between individuals from east Africa also conforms to the relatively larger male effective size and emphasize the necessity of including Ne measures in population and forensic studies. Joint Y-SNP and Y-STR data on more individuals and populations will help to clarify the association between the two Y-chromosome markers and their implication to forensics and better understanding of human evolutionary history in the region.

Key words: Y chromosome, Short tandem repeats, Y-STR, SNPs, East Africa

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SINGLE NUCLEOTIDE POLYMORPHISMS

CHARACTERIZATION OF SINGLE NUCLEOTIDE POLYMORPHISMS ASSOCIATED WITH RESPONSE TO ANTIDEPRESSANT DRUGS IN SUDANESE POPULATION

Authors name: Suaad Balla khalaf alla , Mohamed O Elsiddeig, Muntaser Eltyeb Ibrahim

Affiliation: Institute of Endemic Disease – University of Khartoum.

Background: Antidepressant drugs [AD] prescribed for major depressive disorders are associated with therapeutic failures in approximately 40% of patients after initial dosing. Pharmacogenetic (PGx) variances play a significant role in these failures and therefore, using genetic data in decision-making for population-based dosing may both enhance efficacy and reduce adverse effects. Prior knowledge of allele distributions of the (PGx) biomarkers in different countries can help towards patient stratification for most populations during the drug prescribing process. However, Allele frequency distributions for gene polymorphisms associated with [AD] response in the Sudanese population and Africa in general remains largely not characterized.

Objective: To investigate single nucleotide Polymorphisms [SNPs] affecting several pharmacodynamic and pharmacokinetic variables associated with response to [AD] in Sudanese and to compare the data with the global geographical data reported in gnomAD genome database from different ethnic populations.⁠

Design: Out of 764 SNPs in 7 candidate genes affecting response to [AD] in 242 healthy Sudanese individuals genotype data, a total of 46 SNPs chosen according to deleteriousness and clinical annotation reported in PharmGKB database. Minor allele frequency (MAF) of clinically actionable SNPs compared with gnomaAD genome population frequencies using Chi-square test.

Result: Among deleterious SNPs, nine are unreported in gnomad genome database, two SNPs were common, MAF>5%, SLC6A4 rs138004662 (8%) and ABCB1 rs2032582 (15%). Of the clinically actionable variants, 3 SNPs (ABCB1 rs1045642, rs2032582, and BDNF rs7103411) show significant differences (p-value <0.05) between Sudanese and all other populations with the lowest frequency in Sudanese. ABCB1 rs1272006 was monomorphic (that is, no variation) across all population tested. 2 SNPs (rs7103411 and rs7124442) associated with better response to citalopram is less common in Sudanese compared with other populations.

Conclusion: Since therapeutic decision relies mainly on the US FDA or European Medical Agency guidelines for dosing instructions, understanding of the inter-ethnic differences in the pharmacogenetic is critical to guide more effective global drug prescriptions, Such data will be useful for future clinical and for drug dosage recommendations in the Sudanese population.

Keywords: Antidepressant, SNP, Pharmacogenetics.

 

Presenter name: Suaad Balla Khalafalla Abdalla

Affiliations: Institute of Endemic Diseases- University of Khartoum.

 

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PHARMACOGENETICS OF FLUOROPYRAMIDINES

PHARMACOGENETICS OF FLUOROPYRAMIDINES: ANALYSIS OF DPYD SNPS IN THE SUDANESE POPULATION

Sabah Alrasheed Abdalaziz Alhaj1, Mohammed Omar Elsiddieg Abdallah2, Muntaser Ibrahim3   

  1. Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, P. O. Box 102, ArmyRoad, 11111 Khartoum, Sudan, Sabahalhaj1991@gmail.com
  2. Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, P. O. Box 102, Army Road, 11111 Khartoum, Sudan, melsiddieg@gmail.com
  3. Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, P. O. Box 102, Army Road, 11111 Khartoum, Sudan, mibrahim@iend.org

 

Aim: To contribute towards the DPYD gene database and the Pharmacogenetics Sudanese database reporting for the first time, the frequency and type of sequence variations in the DPYD gene among the Sudanese population.  Furthermore, we aim to analyze the variation spectrum in the DPYD gene by comparing the reported Sudanese frequencies with the global population’s frequencies.

Background: Pharmacogenetics and pharmacogenomics (PGx) researches aim to elucidate the genetic basis for the inter-individual differences in drug response. fluoropyrimidines are among the most frequently prescribed anticancer drugs. Variant analysis of DPYD gene that codes for their key catabolism enzyme may help to predict fluoropyrimidine-related severe toxicity.

Methods: Publicly available genotype array data were analyzed for 242 Sudanese individuals encompassing 18 sub-populations. We reported the frequencies of DPYD variants that had >20 CADD score for further functional analysis. In addition, a total of 38 clinically relevant variants from the DPYD PharmGKB database were extracted and looked for in our data to report their frequencies and compare them with global populations from the gnomAD database.

Results: Of the 1219 variants analyzed, 11 have CADD score > 20. Of the 38 variants, 6 were found in our study population and significant statistical differences were found in the distribution of most of these variants when compared to the global population’s frequencies.

Conclusions: Different variation spectrum is found in the DPYD variants among Sudanese compared with other global populations. Further pharmacogenetic studies are required to investigate and document pharmacogenetic variants in DPYD and other metabolizing enzymes genes to help impact clinical practice.

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Pharmacogenetics of Artemether-Lumefantrine Combination Therapy

The pharmacogenetics of Artemether-Lumefantrine Combination Therapy for Uncomplicated Plasmodium falciparum Malaria in Sudan

 

Hamad Alneel Albagir Ahmed Ali 1, Muntaser Ibrahim 2*

1Department of Microbiology, International University of Africa

2Institute of Endemic Diseases, University Of Khartoum

*Corresponding Author

Emails: hamadalbagir@gmail.com1, Mibrahim@iend.org2*

 

Abstract

Background: Artemether-lumefantrine combination currently recommended as first-line treatment for uncomplicated Plasmodium falciparum malaria in Sudan and substrates of Cytochrome P450 enzymes.

Significant inter-individual variability in the disposition of these drugs has been documented, suggesting the possibility of the influence of genetic factors. It is; therefore, important to obtain the pharmacogenetic profile (or spectrum) of the population in Sudan with respect to these combinations and thereby enable practitioners to predict treatment outcome. The aim of this study was to determine the presence of Cytochrome P450 variant alleles (CYP2C8*2, CYP2C8*3, CYP2B6*6, CYP3A4*1B, CYP3A5*3, and CYP3A5*6 ) in Sudan where malaria is endemic.

Methods: Whole exome sequence data for 55 healthy Sudanese individuals were analyzed to determine

the  allele frequencies of the variants known to impact  artemether-lumefantrine combination.

Results: Allele frequencies of the variants: CYP2C8*2 (rs11572103), CYP2C8*3(rs10509681-

rs11572080), CYP2B6*6 (rs3745274), CYP3A4*1B (rs2740574), CYP3A5*3 (rs776746), CYP3A5*6

(rs10264272)  were found to be 0.081, 0.045, 0.081, 0.354, 0.009, 0.200 and 0.136 respectively.

Conclusion: Prevalence of CYP2C8*2, CYP2C8*3, CYP3A5*3, CYP3A5*6 and CYP2B6*6 variants are common while CYP3A4*1B variants are rare in the Sudanese Exome Data. The frequencies documented in this study are comparable to data acquired from earlier studies on African populations. Pharmacogenomics data, such as that exhibited in this paper, produce a basis for further studies on the impact of polymorphism in Artemether-lumefantrine combination safety and efficacy.

Keywords: Cytochrome P450, Artemisinin-lumefantrine combination therapy, Sudan, uncomplicated

Plasmodium falciparum malaria.

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DELETION OF GLUTATHIONE S-TRANSFERASE THETA 1

DELETION OF GLUTATHIONE S-TRANSFERASE THETA 1 IN FOUR SUDANESE ETHNIC GROUPS

Anadil Ahmed Alsubki Alhassan1, Muntaser  Eltayeb Ibrahim2

1 Department of Molecular Biology, Institute of endemic disease, Qasr street, Khartoum, Sudan,  anadilalsubki@gmail.com

2Department of Molecular Biology, Institute of endemic disease, Qasr street, Khartoum, Sudan,mibrahim@iend.org

 Background: Glutathione S-transferases (GSTs) are drug-metabolizing enzymes important in the transformation of xenobiotics, carcinogens, oxygen free radicals and drugs. Pharmacogenomics researches suggested interethnic variation in GST allele’s frequencies. Polymorphisms of GST genes contribute to susceptibility to cancer, environmental risk factors and variability in pharmacotherapy responses.

Aim: To determine the prevalence of GSTT1 null genotype in different ethnic groups and if ethnicity has a role in the allelic distribution.

Individuals and method: GSTT1 null allele genotyped by Multiplex PCR in 120 healthy individuals .

Result:  Hausa and Nilotic have the highest frequencies of the null allele, Beja Bani Amir has the lowest frequency, Beja Bani Amir and Beja Hadendowa frequencies are different from each other although they belong to the same ethnic group ,however, the difference is not statistically significant by Fisher exact test.

Conclusion: Ethnic differences has no effect in GSTT1 null genotype disturbution in groups under study.

 

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CLARITHROMYCIN RESISTANCE OF CLINICAL HELICOBACTER PYLORI

DETECTION AND CLARITHROMYCIN RESISTANCE OF CLINICAL HELICOBACTER PYLORI ISOLATES IN INDIAN POPULATION

Mr. Angesom Abraham 1, 2 , Dr. Asish Kumar Mukhopadhyay 1

  1. National Institute of Cholera and Enteric Diseases Division of Bacteriology, Kolkata, India. 2. Eritrea Institute of Technology, Mai-Nefhi, Eritrea.

Aim: This study is aimed at detecting the presence of H. pylori and the resistance to clarithromycin in Indian population.

Background: Helicobacter pylori is the most bacterial infection worldwide, infecting almost half of people in developed countries and 80% of people in developing countries (Go MF, 2002).  Clarithromycin therapy is effective in eradicating Helicobacter pylori. However, the resistance of H. pylori to clarithromycin is increasingly reported and it is associated to the point mutation in the 23s rRNA gene (Versalovic et al, 1996).

Methods: Helicobacter pylori is detected in the strains by culturing, positive test for Rapid Urease Test (RUT), oxidase, catalase and positive test to Urease gene by Normal-PCR (amplifying the Urease gene). Clarithromycin resistance detected by MAMA (Mismatch Amplification Mutational Assay)-PCR (amplifying the 23s rRNA gene) and antimicrobial susceptibility test.

Results: All the 40 strains were positive for Helicobacter pylori by culture and positive to urease gene by PCR. Out of the 40 strains 36 (90 %) were sensitive to clarithromycin and 4 (10 %) were resistant to clarithromycin by the PCR (amplifying the 23s rRNA gene). In addition, the MIC method was used and the 36 strains were sensitive to the concentration of 0.125 µg/ml of clarithromycin. However, the remaining 4 (10 %) are able to grow up to >2 µg/ml, as they are resistant to the action of clarithromycin. PCR results showed consistency with CLR MIC data that is ≥ 2 µg/ml MIC value for CLR-resistant strains and MICs ≤ 0.125µg/ml for CLR-sensitive strains.

Conclusions: The resistance of Helicobacter pylori to clarithromycin antibiotic is emerging in the Indian population. As a result, researchers has to work hard on the eradication of Helicobacter pylori infection by designing a better drug (antibiotic) based on the genetic features of the bacteria.

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