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 Grandy, Trefor Jenkins, Judith R. Kidd

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    163 Citations (Scopus)

    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 heterozy-gosity 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 disequilibri um 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.

    Original languageEnglish (US)
    Pages (from-to)211-227
    Number of pages17
    JournalHuman Genetics
    Volume103
    Issue number2
    DOIs
    StatePublished - 1998

    Fingerprint

    Linkage Disequilibrium
    Haplotypes
    Population
    Microsatellite Repeats
    Surveys and Questionnaires
    Chromosomes
    Genetic Drift
    Far East
    Dopamine D2 Receptors
    Mutation Rate
    Genetic Recombination

    ASJC Scopus subject areas

    • Genetics(clinical)
    • Genetics

    Cite this

    Kidd, K. K., Morar, B., Castiglione, C. M., Zhao, H., Pakstis, A. J., Speed, W. C., ... Kidd, J. R. (1998). A global survey of haplotype frequencies and linkage disequilibrium at the DRD2 locus. Human Genetics, 103(2), 211-227. https://doi.org/10.1007/s004390050809

    A global survey of haplotype frequencies and linkage disequilibrium at the DRD2 locus. / Kidd, Kenneth K.; Morar, Bharti; Castiglione, Carmela M.; Zhao, Hongyu; Pakstis, Andrew J.; Speed, William C.; Bonne-Tamir, Batsheva; Lu, Ru Band; Goldman, David; Lee, Chaeyoung; Nam, Yong Suk; Grandy, David; Jenkins, Trefor; Kidd, Judith R.

    In: Human Genetics, Vol. 103, No. 2, 1998, p. 211-227.

    Research output: Contribution to journalArticle

    Kidd, KK, Morar, B, Castiglione, CM, Zhao, H, Pakstis, AJ, Speed, WC, Bonne-Tamir, B, Lu, RB, Goldman, D, Lee, C, Nam, YS, Grandy, D, Jenkins, T & Kidd, JR 1998, 'A global survey of haplotype frequencies and linkage disequilibrium at the DRD2 locus', Human Genetics, vol. 103, no. 2, pp. 211-227. https://doi.org/10.1007/s004390050809
    Kidd KK, Morar B, Castiglione CM, Zhao H, Pakstis AJ, Speed WC et al. A global survey of haplotype frequencies and linkage disequilibrium at the DRD2 locus. Human Genetics. 1998;103(2):211-227. https://doi.org/10.1007/s004390050809
    Kidd, Kenneth K. ; Morar, Bharti ; Castiglione, Carmela M. ; Zhao, Hongyu ; Pakstis, Andrew J. ; Speed, William C. ; Bonne-Tamir, Batsheva ; Lu, Ru Band ; Goldman, David ; Lee, Chaeyoung ; Nam, Yong Suk ; Grandy, David ; Jenkins, Trefor ; Kidd, Judith R. / A global survey of haplotype frequencies and linkage disequilibrium at the DRD2 locus. In: Human Genetics. 1998 ; Vol. 103, No. 2. pp. 211-227.
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