Human Genetics

, Volume 132, Issue 9, pp 987–999

Patterns of nucleotide and haplotype diversity at ICAM-1 across global human populations with varying levels of malaria exposure

  • 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
Original Investigation

DOI: 10.1007/s00439-013-1284-5

Cite this article as:
Gomez, F., Tomas, G., Ko, WY. et al. Hum Genet (2013) 132: 987. doi:10.1007/s00439-013-1284-5

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-1Kilifi allele, that are correlated with malaria endemicity. We show that the ICAM-1Kilifi 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.

Supplementary material

439_2013_1284_MOESM1_ESM.pdf (11.4 mb)
Supplementary material 1 ICAM-1 haplotypes used in network analysis. The SNPs included here are sites with a minor allele frequency ≥2% in each continental region (i.e. Africa, Asia, and Europe). The blue boxes represent the common allele and the yellow boxes represent the rare allele (PDF 11709 kb)
439_2013_1284_MOESM2_ESM.pdf (16.5 mb)
Supplementary material 2 Inferred haplotypes at ICAM-1 using all 87 sites identified in the sequenced regions. The blue boxes represent the common allele and the yellow boxes represent the rare allele (PDF 16894 kb)
439_2013_1284_MOESM3_ESM.xlsx (54 kb)
Supplementary material 3 Allele frequencies for each SNP identified. SNPs are numbered according to the +1 ATG start in ICAM-1 reference (NT_011295). Rs ID numbers are indicated where applicable. SNPs found in exons are labeled s and r. This refers to synonymous SNPs (s) and non-synonymous ( r ) replacement SNPs. Frequency of each allele is shown. f(A) refers to overall dataset major allele f(a) refers to overall dataset minor allele. Population abbreviations follow abbreviations in table 1, with the addition of a country of origin prefix. CA=Cameroon, CH= Chad, KE =Kenya, SD = Sudan, TZ= Tanzania (XLSX 54 kb)
439_2013_1284_MOESM4_ESM.xlsx (47 kb)
Supplementary material 4 ICAM-1 phased SNP haplotypes. SNPs are numbered according to the +1 ATG start in ICAM-1 reference (NT_011295). The number of haplotypes observed in each population is shown. All population abbreviations follow abbreviation presented in Table 1. The asterick (*) indicates a haplotype included in the network analysis. When present, the allele in P. troglodytes is indicated. SNPs found in the exons are labeled s and r. This refers to synonymous SNPs (s) and non-synonymous ( r ) replacement SNPs. (XLSX 46 kb)
439_2013_1284_MOESM5_ESM.pdf (60 kb)
Supplementary material 5 McDonald Kreitman test. Rpd = ratio of polymorphism/divergence (A) All human chromosomes (B) All African chromosomes (C) All non-African chromosomes (PDF 59 kb)
439_2013_1284_MOESM6_ESM.pdf (61 kb)
Supplementary material 6 Malaria endemicity correlation r2 and p values for each non–singleton SNP. SNPs are numbered according to the +1 ATG start in ICAM-1 reference (NT_011295). Rs5491 is indicated. Thick black line separates r2 values in the top 5% of distributions shown in figure 4 (PDF 61 kb)
439_2013_1284_MOESM7_ESM.pdf (53 kb)
Supplementary material 7 PCR primers used to amplify regions I, II and III of ICAM-1 described here (PDF 53 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Felicia Gomez
    • 1
    • 2
    • 3
    • 12
  • Gil Tomas
    • 4
  • Wen-Ya Ko
    • 1
    • 10
  • Alessia Ranciaro
    • 1
  • Alain Froment
    • 5
  • Muntaser Ibrahim
    • 6
  • Godfrey Lema
    • 7
  • Thomas B. Nyambo
    • 7
  • Sabah A. Omar
    • 8
  • Charles Wambebe
    • 9
  • Jibril B. Hirbo
    • 1
  • Jorge Rocha
    • 4
    • 10
    • 11
  • Sarah A. Tishkoff
    • 1
  1. 1.Department of Genetics and Biology, School of Medicine and School of Arts and SciencesUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Hominid Paleobiology Doctoral Program, Department of AnthropologyThe George Washington UniversityWashingtonUSA
  3. 3.Center for the Advanced Study of Hominid Paleobiology, Department of AnthropologyThe George Washington UniversityWashingtonUSA
  4. 4.IPATIMUP-Instituto de Patologia e Imunologia Molecular da Universidade do PortoPortoPortugal
  5. 5.UMR 208, Institut de Recherche pour le de′veloppementMuse′um National d’Histoire NaturelleParisFrance
  6. 6.Department of Molecular Biology, Institute of Endemic DiseasesUniversity of Khartoum15-KhartoumSudan
  7. 7.Department of BiochemistryMuhimbili University of Health and Allied SciencesDar es SalaamTanzania
  8. 8.Kenya Medical Research InstituteCenter for Biotechnology Research and DevelopmentNairobiKenya
  9. 9.International Biomedical Research in AfricaAbujaNigeria
  10. 10.CIBIO-Centro de Investigação em Biodiversidade e Recursos GenéticosUniversidade do PortoVairãoPortugal
  11. 11.Departamento de BiologiaFaculdade de Ciências, Universidade do PortoPortoPortugal
  12. 12.Washington University School of Medicine, Division of Biostatistics and Statistical GenomicsSt. LouisUSA