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Human Genetics

, Volume 103, Issue 2, pp 211–227 | Cite as

A global survey of haplotype frequencies and linkage disequilibrium at the DRD2 locus

  • Kenneth K. Kidd
  • Bharti Morar
  • Carmela M. Castiglione
  • Hongyu Zhao
  • Andrew J. Pakstis
  • William C. Speed
  • Batsheva Bonne-Tamir
  • Ru-Band Lu
  • David Goldman
  • Chaeyoung Lee
  • Yong Suk Nam
  • David K. Grandy
  • Trefor Jenkins
  • Judith R. Kidd
Original Investigation

Abstract

A four-site haplotype system at the dopamine D2 receptor locus (DRD2) has been studied in a global sample of 28 distinct populations. The haplotype system spans about 25 kb, encompassing the coding region of the gene. The four individual markers include three TaqI restriction site polymorphisms (RSPs) – TaqI “A”, “B”, and “D” sites – and one dinucleotide short tandem repeat polymorphism (STRP). All four of the marker systems are polymorphic in all regions of the world and in most individual populations. The haplotype system shows the highest average heterozygosity in Africa, a slightly lower average heterozygosity in Europe, and the lowest average heterozygosities in East Asia and the Americas. Across all populations, 20 of the 48 possible haplotypes reached a frequency of at least 5% in at least one population sample. However, no single population had more than six haplotypes reaching that frequency. In general, African populations had more haplotypes present in each population and more haplotypes occurring at a frequency of at least 5% in that population. Permutation tests for significance of overall disequilibrium (all sites considered simultaneously) were highly significant (P<0.001) in all 28 populations. Except for three African samples, the pairwise disequilibrium between the outermost RSP markers, TaqI “B” and “A”, was highly significant with D’ values greater than 0.8; in two of those exceptions the RSP marker was not polymorphic. Except for those same two African populations, the 16-repeat allele at the STRP also showed highly significant disequilibrium with the TaqI “B” site in all populations, with D’ values usually greater than 0.7. Only four haplotypes account for more than 70% of all chromosomes in virtually all non-African populations, and two of those haplotypes account for more than 70% of all chromosomes in most East Asian and Amerindian populations. A new measure of the amount of overall disequilibrium shows least disequilibrium in African populations, somewhat more in European populations, and the greatest amount in East Asian and Amerindian populations. This pattern seems best explained by random genetic drift with low levels of recombination, a low mutation rate at the STRP, and essentially no recurrent mutation at the RSP sites, all in conjunction with an “Out of Africa” model for recent human evolution.

Keywords

African Population Recurrent Mutation Average Heterozygosity Random Genetic Drift Site Polymorphism 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • Kenneth K. Kidd
    • 1
  • Bharti Morar
    • 3
  • Carmela M. Castiglione
    • 1
  • Hongyu Zhao
    • 2
  • Andrew J. Pakstis
    • 1
  • William C. Speed
    • 1
  • Batsheva Bonne-Tamir
    • 4
  • Ru-Band Lu
    • 5
  • David Goldman
    • 6
  • Chaeyoung Lee
    • 7
  • Yong Suk Nam
    • 8
  • David K. Grandy
    • 9
  • Trefor Jenkins
    • 3
  • Judith R. Kidd
    • 1
  1. 1.Department of Genetics, Yale University School of Medicine, New Haven, CT 06520-8005, USA e-mail: kidd@biomed.med.yale.edu, Tel.: (203) 785 2654, Fax: (203) 785 6568US
  2. 2.Department of Epidemiology, Yale University School of Medicine, New Haven, CT 06520-8005, USAUS
  3. 3.Department of Human Genetics, SAIMR and University of the Witwatersrand, Johannesburg, South AfricaZA
  4. 4.Department of Human Genetics, Sackler School of Medicine, Tel Aviv University, IsraelIL
  5. 5.Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, TaiwanTW
  6. 6.Laboratory of Neurogenetics, NIAAA/NIH, 12501 Washington Ave, Rockville, MD 20852, USAUS
  7. 7.Laboratory of Statistical Genetics, Institute of Environment and Life Science, Hallym University, Chuncheon, 200-702, KoreaKR
  8. 8.Department of Legal Medicine, Korea University, Seoul, 136-701, KoreaKR
  9. 9.Department of Physiology and Pharmacology, Oregon Health Sciences University, Portland, OR 92701-3098, USAUS

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