TY - JOUR
T1 - A global survey of haplotype frequencies and linkage disequilibrium at the DRD2 locus
AU - Kidd, Kenneth K.
AU - Morar, Bharti
AU - Castiglione, Carmela M.
AU - Zhao, Hongyu
AU - Pakstis, Andrew J.
AU - Speed, William C.
AU - Bonne-Tamir, Batsheva
AU - Lu, Ru Band
AU - Goldman, David
AU - Lee, Chaeyoung
AU - Nam, Yong Suk
AU - Grandy, David K.
AU - Jenkins, Trefor
AU - Kidd, Judith R.
N1 - Funding Information:
Acknowledgements We want to acknowledge and thank all of the individuals who volunteered to provide blood samples for this and similar studies of normal genetic variation. We also want to thank the several colleagues who helped collect the samples. These studies were primarily supported by USPHS grants AA09379 and MH39239 to KKK, and by NIMH grant MH30929 in support of the Mental Health Clinical Research Center at Yale and by NSF grant SBR9632509 to JRK. Additional support was provided by the South Africa Medical Research Council, the University of the Witwatersrand, and the South African Institute for Medical Research to TJ; by the National Science Council of Taiwan (NSC86–2314-B016–116Y) and the Department of Health of Taiwan (DOH86-IIR-612) to RBL; and by a grant from the Hallym Academy of Sciences, Hallym University to CL. Collection of some of the samples was also supported by a grant from the Alfred P. Sloan Foundation to KKK.
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0031685062&partnerID=8YFLogxK
U2 - 10.1007/s004390050809
DO - 10.1007/s004390050809
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C2 - 9760208
AN - SCOPUS:0031685062
SN - 0340-6717
VL - 103
SP - 211
EP - 227
JO - Human Genetics
JF - Human Genetics
IS - 2
ER -