, Volume 56, Issue 4, pp 225–237 | Cite as

SNP haplotypes and allele frequencies show evidence for disruptive and balancing selection in the human leukocyte receptor complex

  • Paul J. Norman
  • Mark A. Cook
  • B. Sean Carey
  • Christine V. F. Carrington
  • David H. Verity
  • Kamran Hameed
  • D. Dan Ramdath
  • Dasnayanee Chandanayingyong
  • Mark Leppert
  • Henry A. F. Stephens
  • R. W. Vaughan
Original Paper


The human leukocyte receptor complex (LRC) of Chromosome 19q13.4 encodes polymorphic and highly homologous genes that are expressed by cells of the immune system and regulate their function. There is an enormous diversity at the LRC, most particularly the variable number of killer cell immunoglobulin-like receptor (KIR) genes. KIR have been associated with several disease processes due to their interaction with polymorphic human leukocyte antigen class I molecules. We have assessed haplotype compositions, linkage disequilibrium patterns and allele frequencies in two Caucasoid population samples (n=54, n=100), using a composite of single-nucleotide polymorphism (SNP) markers and high-resolution, allele-specific molecular genotyping. Particular KIR loci segregated with SNP and other markers, forming two blocks that were separated by a region with a greater history of recombination. The KIR haplotype composition and allele frequency distributions were consistent with KIR having been subject to balancing selection (Watterson’s F: P=0.001). In contrast, there was a high inter-population heterogeneity measure for the LRC-encoded leukocyte immunoglobulin-like receptor A3 (LILRA3), indicating pathogen-driven disruptive selection (Wright’s FST=0.32). An assessment of seven populations representative of African, Asian and Caucasoid ethnic groups (total n=593) provided little evidence for long-range LRC haplotypes. The different natural selection pressures acting on each locus may have contributed to a lack of linkage disequilibrium between them.


KIR Leukocyte receptor complex Natural killer cell SNP Haplotype Natural selection 


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Paul J. Norman
    • 1
  • Mark A. Cook
    • 2
    • 3
  • B. Sean Carey
    • 1
    • 4
  • Christine V. F. Carrington
    • 5
  • David H. Verity
    • 6
  • Kamran Hameed
    • 7
  • D. Dan Ramdath
    • 5
  • Dasnayanee Chandanayingyong
    • 8
  • Mark Leppert
    • 9
  • Henry A. F. Stephens
    • 1
    • 4
  • R. W. Vaughan
    • 1
  1. 1.Clinical Transplantation LaboratoryGuy’s HospitalLondonUK
  2. 2.Cancer Research UK Institute for Cancer StudiesUniversity of BirminghamBirminghamUK
  3. 3.Histocompatibility and ImmunogeneticsNational Blood ServiceBirminghamUK
  4. 4.Institute of Urology and NephrologyUniversity CollegeLondonUK
  5. 5.Department of Pre-Clinical Sciences, Faculty of Medical SciencesUniversity of the West IndiesSt. AugustineTrinidad and Tobago
  6. 6.Department of OpthalmologySt Thomas’ Hospital-King’s CollegeLondonUK
  7. 7.Department of MedicineAga Khan University HospitalKarachiPakistan
  8. 8.Department of Transfusion MedicineSiriraj HospitalBangkokThailand
  9. 9.Eccles Centre for Human GeneticsUniversity of UtahSalt Lake CityUSA

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