1. Mutaz A. A. Mustafa, A. A. M. Elhassan, M. E. Ibrahim Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan E-mail: mtz88@hotmail.co.uk Objectives:Discussion Objectives - To analyze these SNPs using different bioinformatics software to determine their effect on the structure, function and stability of interleukins. - To correlate different interleukins genotypes with serum IgE level and susceptibility to malaria. Objectives - To analyze these SNPs using different bioinformatics software to determine their effect on the structure, function and stability of interleukins. - To correlate different interleukins genotypes with serum IgE level and susceptibility to malaria. Introduction Koka is a village located in eastern Sudan inhabited by Hausa tribe. It is endemic with both malaria and visceral leishmaniasis. A group of SNPs in 5q31 region which houses Interleukin genes were previously genotyped by Leishmaniasis research group in Sudan and found to have significant excess in heterozygosity and departure from HWE. [1] [1] Natural selection was the most likely culprit because of the high mortality of these two diseases in the area. Introduction Koka is a village located in eastern Sudan inhabited by Hausa tribe. It is endemic with both malaria and visceral leishmaniasis. A group of SNPs in 5q31 region which houses Interleukin genes were previously genotyped by Leishmaniasis research group in Sudan and found to have significant excess in heterozygosity and departure from HWE. [1] [1] Natural selection was the most likely culprit because of the high mortality of these two diseases in the area. Methods The SNPs studied, heterozygosity level and DHWE is shown in the following table (Elhassan et al, 2012) : Different bioinformatics softwares were used to analyse SNPs’ role in transcription factor binding, splicing, miRNA binding, mRNA stability and SNP to SNP interactions. Methods The SNPs studied, heterozygosity level and DHWE is shown in the following table (Elhassan et al, 2012) : Different bioinformatics softwares were used to analyse SNPs’ role in transcription factor binding, splicing, miRNA binding, mRNA stability and SNP to SNP interactions. Results and Discussion The SNPs in IL-4 and IL-13 are found to affect the binding of many TFs. The SNP in IL-5 is found to affect stability of IL- 5 mRNA by changing a stem loop structure. Serum IgE level increased in a stepwise manner with different IL-4 rs734244 genotypes: The haplotype of the lowest expression profile in silico is associated with significantly lower risk of malaria infection Results and Discussion The SNPs in IL-4 and IL-13 are found to affect the binding of many TFs. The SNP in IL-5 is found to affect stability of IL- 5 mRNA by changing a stem loop structure. Serum IgE level increased in a stepwise manner with different IL-4 rs734244 genotypes: The haplotype of the lowest expression profile in silico is associated with significantly lower risk of malaria infection High cytokine TH2 profile correlates with rapid malaria parasite clearance (i.e. protective) but high level also is associated with susceptibility to disseminated leishmaniasis. [2,3,4] [2,3,4] 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. High cytokine TH2 profile correlates with rapid malaria parasite clearance (i.e. protective) but high level also is associated with susceptibility to disseminated leishmaniasis. [2,3,4] [2,3,4] 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. References -1A. A. M. Elhassan, A. A. Hussein, H. S. Mohamed, K. Rockett, D. Kwiatkowski, A. M. Elhassan, and M. E. Ibrahim, The 5q31 region in two African populations as a facet of natural selection by infectious diseases ГЕНЕТИКА, 2013, том 49, № 2, с. 1–10. 2-D. Prakash, Constantin Fesel3, Rajendra Jain, Pierre-André Cazenave, Gyan Chandra Mishra and Sylviane Pied, Clusters of Cytokines Determine Malaria Severity in Plasmodium falciparum–Infected Patients from Endemic Areas of Central India, Oxford Journals, Medicine,The Journal of Infectious Diseases, Volume 194, Issue 2 Pp. 198-207. 3-Erika van den Bogaart, Al-Badawi A Talha2 Masja Straetemans, Cytokine profiles amongst Sudanese patients with visceral leishmaniasis and malaria co-infections, BMC Immunology 2014, 15:16 doi:10.1186/1471-2172-15-16. 4-HS Mohamed, ME Ibrahim, EN Miller, CS Peacock, EAG Khalil, HJ Cordell, JMM Howson, AM El Hassan, REH Bereir and JM Blackwell, Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1 Genes and Immunity (2003) 4, 351–355 & 2003 Nature Publishing Group All rights reserved 1466-4879/03. References -1A. A. M. Elhassan, A. A. Hussein, H. S. Mohamed, K. Rockett, D. Kwiatkowski, A. M. Elhassan, and M. E. Ibrahim, The 5q31 region in two African populations as a facet of natural selection by infectious diseases ГЕНЕТИКА, 2013, том 49, № 2, с. 1–10. 2-D. Prakash, Constantin Fesel3, Rajendra Jain, Pierre-André Cazenave, Gyan Chandra Mishra and Sylviane Pied, Clusters of Cytokines Determine Malaria Severity in Plasmodium falciparum–Infected Patients from Endemic Areas of Central India, Oxford Journals, Medicine,The Journal of Infectious Diseases, Volume 194, Issue 2 Pp. 198-207. 3-Erika van den Bogaart, Al-Badawi A Talha2 Masja Straetemans, Cytokine profiles amongst Sudanese patients with visceral leishmaniasis and malaria co-infections, BMC Immunology 2014, 15:16 doi:10.1186/1471-2172-15-16. 4-HS Mohamed, ME Ibrahim, EN Miller, CS Peacock, EAG Khalil, HJ Cordell, JMM Howson, AM El Hassan, REH Bereir and JM Blackwell, Genetic susceptibility to visceral leishmaniasis in The Sudan: linkage and association with IL4 and IFNGR1 Genes and Immunity (2003) 4, 351–355 & 2003 Nature Publishing Group All rights reserved 1466-4879/03. This is probably the first work of its kind to demonstrate the phenomenon of overdominance in a regulatory DNA region. MalariaVL Low cytokine TH2 profile is not good with malaria High cytokine TH2 profile is not good with VL Acknowledgement The authors wish to acknowledge the cooperation of Koka villagers and the EviMalar European Network of Excellence. Acknowledgement The authors wish to acknowledge the cooperation of Koka villagers and the EviMalar European Network of Excellence.