title: Patterns of nucleotide and haplotype diversity at ICAM-1 across global human populations with varying levels of malaria exposure.
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.
authors.affiliation: Department of Genetics and Biology, School of Medicine and School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, 19104, USA. fgomez@mail.med.upenn.edu
authors.forename: Felicia
authors.initials: F
authors.lastname: Gomez
authors.forename: Gil
authors.initials: G
authors.lastname: Tomas
authors.forename: Wen-Ya
authors.initials: WY
authors.lastname: Ko
authors.forename: Alessia
authors.initials: A
authors.lastname: Ranciaro
authors.forename: Alain
authors.initials: A
authors.lastname: Froment
authors.forename: Muntaser
authors.initials: M
authors.lastname: Ibrahim
authors.forename: Godfrey
authors.initials: G
authors.lastname: Lema
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Nyambo
authors.forename: Sabah A
authors.initials: SA
authors.lastname: Omar
authors.forename: Charles
authors.initials: C
authors.lastname: Wambebe
authors.forename: Jibril B
authors.initials: JB
authors.lastname: Hirbo
authors.forename: Jorge
authors.initials: J
authors.lastname: Rocha
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Tishkoff
mesh_terms: D001483:Base Sequence; D044383:Black People / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005828:Genetics, Population; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D015810:Linkage Disequilibrium; D008288:Malaria / Q000208:ethnology / Q000235:genetics*; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D017931:DNA Primers; D018799:Intercellular Adhesion Molecule-1