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Patterns of nucleotide and haplotype diversity at ICAM-1 across global human populations with varying levels of malaria exposure
Authors:Felicia Gomez  Gil Tomas  Wen-Ya Ko  Alessia Ranciaro  Alain Froment  Muntaser Ibrahim  Godfrey Lema  Thomas B Nyambo  Sabah A Omar  Charles Wambebe  Jibril B Hirbo  Jorge Rocha  Sarah A Tishkoff
Institution:1. Department of Genetics and Biology, School of Medicine and School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, 19104, USA
12. Washington University School of Medicine, Division of Biostatistics and Statistical Genomics, St. Louis, MO, 63108, USA
2. Hominid Paleobiology Doctoral Program, Department of Anthropology, The George Washington University, Washington, DC, 20052, USA
3. Center for the Advanced Study of Hominid Paleobiology, Department of Anthropology, The George Washington University, Washington, DC, 20052, USA
4. IPATIMUP-Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Porto, Portugal
10. CIBIO-Centro de Investiga??o em Biodiversidade e Recursos Genéticos, Universidade do Porto, Vair?o, Portugal
5. UMR 208, Institut de Recherche pour le de′veloppement, Muse′um National d’Histoire Naturelle, Muse′ e de l’Homme, 75116, Paris, France
6. Department of Molecular Biology, Institute of Endemic Diseases, University of Khartoum, 15-Khartoum, Sudan
7. Department of Biochemistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania
8. Kenya Medical Research Institute, Center for Biotechnology Research and Development, 54840-00200, Nairobi, Kenya
9. International Biomedical Research in Africa, Abuja, Nigeria
11. Departamento de Biologia, Faculdade de Ciências, Universidade do Porto, Porto, Portugal
Abstract:Malaria is one of the strongest selective pressures in recent human evolution. African populations have been and continue to be at risk for malarial infections. However, few studies have re-sequenced malaria susceptibility loci across geographically and genetically diverse groups in Africa. We examined nucleotide diversity at Intercellular adhesion molecule-1 (ICAM-1), a malaria susceptibility candidate locus, in a number of human populations with a specific focus on diverse African ethnic groups. We used tests of neutrality to assess whether natural selection has impacted this locus and tested whether SNP variation at ICAM-1 is correlated with malaria endemicity. We observe differing patterns of nucleotide and haplotype variation in global populations and higher levels of diversity in Africa. Although we do not observe a deviation from neutrality based on the allele frequency distribution, we do observe several alleles at ICAM-1, including the ICAM-1 Kilifi allele, that are correlated with malaria endemicity. We show that the ICAM-1 Kilifi allele, which is common in Africa and Asia, exists on distinct haplotype backgrounds and is likely to have arisen more recently in Asia. Our results suggest that correlation analyses of allele frequencies and malaria endemicity may be useful for identifying candidate functional variants that play a role in malaria resistance and susceptibility.
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