• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of ajhgLink to Publisher's site
Am J Hum Genet. Dec 1995; 57(6): 1445–1456.
PMCID: PMC1801414

Evolution of Haplotypes at the DRD2 Locus

Abstract

We present here the first evolutionary perspective on haplotypes at DRD2, the locus for the dopamine D2 receptor. The dopamine D2 receptor plays a critical role in the functioning of many neural circuits in the human brain. If functionally relevant variation at the DRD2 locus exists, understanding the evolution of haplotypes on the basis of polymorphic sites encompassing the gene should provide a powerful framework for identifying that variation. Three DRD2 polymorphisms (TaqI “A” and “B” RFLPs and the (CA)n short tandem repeat polymorphism) encompassing the coding sequences have been studied in 15 populations; these markers are polymorphic in all the populations studied, and they display strong and significant linkage disequilibria with each other. The common haplotypes for the two TaqI RFLPs are separately derived from the ancestral haplotype but predate the spread of modern humans around the world. The knowledge of how the various haplotypes have evolved, the allele frequencies of the haplotypes in human populations, and the physical relationships of the polymorphisms to each other and to the functional parts of the gene should now allow proper design and interpretation of association studies.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.0M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Anderson MA, Gusella JF. Use of cyclosporin A in establishing Epstein-Barr virus-transformed human lymphoblastoid cell lines. In Vitro. 1984 Nov;20(11):856–858. [PubMed]
  • Araki K, Kuwano R, Morii K, Hayashi S, Minoshima S, Shimizu N, Katagiri T, Usui H, Kumanishi T, Takahashi Y. Structure and expression of human and rat D2 dopamine receptor genes. Neurochem Int. 1992 Jul;21(1):91–98. [PubMed]
  • Balazs I, Neuweiler J, Gunn P, Kidd J, Kidd KK, Kuhl J, Mingjun L. Human population genetic studies using hypervariable loci. I. Analysis of Assamese, Australian, Cambodian, Caucasian, Chinese and Melanesian populations. Genetics. 1992 May;131(1):191–198. [PMC free article] [PubMed]
  • Barr CL, Kidd KK. Population frequencies of the A1 allele at the dopamine D2 receptor locus. Biol Psychiatry. 1993 Aug 15;34(4):204–209. [PubMed]
  • Bolos AM, Dean M, Lucas-Derse S, Ramsburg M, Brown GL, Goldman D. Population and pedigree studies reveal a lack of association between the dopamine D2 receptor gene and alcoholism. JAMA. 1990 Dec 26;264(24):3156–3160. [PubMed]
  • Bowcock AM, Bucci C, Hebert JM, Kidd JR, Kidd KK, Friedlaender JS, Cavalli-Sforza LL. Study of 47 DNA markers in five populations from four continents. Gene Geogr. 1987 Apr;1(1):47–64. [PubMed]
  • Bowcock AM, Hebert JM, Mountain JL, Kidd JR, Rogers J, Kidd KK, Cavalli-Sforza LL. Study of an additional 58 DNA markers in five human populations from four continents. Gene Geogr. 1991 Dec;5(3):151–173. [PubMed]
  • Bowcock AM, Kidd JR, Mountain JL, Hebert JM, Carotenuto L, Kidd KK, Cavalli-Sforza LL. Drift, admixture, and selection in human evolution: a study with DNA polymorphisms. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):839–843. [PMC free article] [PubMed]
  • Cavalli-Sforza LL, Kidd JR, Kidd KK, Bucci C, Bowcock AM, Hewlett BS, Freidlaender JS. DNA markers and genetic variation in the human species. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):411–417. [PubMed]
  • Dal Toso R, Sommer B, Ewert M, Herb A, Pritchett DB, Bach A, Shivers BD, Seeburg PH. The dopamine D2 receptor: two molecular forms generated by alternative splicing. EMBO J. 1989 Dec 20;8(13):4025–4034. [PMC free article] [PubMed]
  • Feinberg AP, Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. [PubMed]
  • Gandelman KY, Harmon S, Todd RD, O'Malley KL. Analysis of the structure and expression of the human dopamine D2A receptor gene. J Neurochem. 1991 Mar;56(3):1024–1029. [PubMed]
  • Gejman PV, Ram A, Gelernter J, Friedman E, Cao Q, Pickar D, Blum K, Noble EP, Kranzler HR, O'Malley S, et al. No structural mutation in the dopamine D2 receptor gene in alcoholism or schizophrenia. Analysis using denaturing gradient gel electrophoresis. JAMA. 1994 Jan 19;271(3):204–208. [PubMed]
  • Gelernter J, Pakstis AJ, Pauls DL, Kurlan R, Gancher ST, Civelli O, Grandy D, Kidd KK. Gilles de la Tourette syndrome is not linked to D2-dopamine receptor. Arch Gen Psychiatry. 1990 Nov;47(11):1073–1077. [PubMed]
  • Gelernter J, Pauls DL, Leckman J, Kidd KK, Kurlan R. D2 dopamine receptor alleles do not influence severity of Tourette's syndrome. Results from four large kindreds. Arch Neurol. 1994 Apr;51(4):397–400. [PubMed]
  • Giuffra LA, Lichter P, Wu JS, Kennedy JL, Pakstis AJ, Rogers J, Kidd JR, Harley H, Jenkins T, Ward DC, et al. Genetic and physical mapping and population studies of a fibronectin receptor beta-subunit-like sequence on human chromosome 19. Genomics. 1990 Oct;8(2):340–346. [PubMed]
  • Goldman D, Brown GL, Albaugh B, Robin R, Goodson S, Trunzo M, Akhtar L, Lucas-Derse S, Long J, Linnoila M, et al. DRD2 dopamine receptor genotype, linkage disequilibrium, and alcoholism in American Indians and other populations. Alcohol Clin Exp Res. 1993 Apr;17(2):199–204. [PubMed]
  • Grandy DK, Litt M, Allen L, Bunzow JR, Marchionni M, Makam H, Reed L, Magenis RE, Civelli O. The human dopamine D2 receptor gene is located on chromosome 11 at q22-q23 and identifies a TaqI RFLP. Am J Hum Genet. 1989 Nov;45(5):778–785. [PMC free article] [PubMed]
  • Grandy DK, Marchionni MA, Makam H, Stofko RE, Alfano M, Frothingham L, Fischer JB, Burke-Howie KJ, Bunzow JR, Server AC, et al. Cloning of the cDNA and gene for a human D2 dopamine receptor. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9762–9766. [PMC free article] [PubMed]
  • Grandy DK, Zhang Y, Civelli O. PCR detection of the TaqA RFLP at the DRD2 locus. Hum Mol Genet. 1993 Dec;2(12):2197–2197. [PubMed]
  • Hauge XY, Grandy DK, Eubanks JH, Evans GA, Civelli O, Litt M. Detection and characterization of additional DNA polymorphisms in the dopamine D2 receptor gene. Genomics. 1991 Jul;10(3):527–530. [PubMed]
  • Hawley ME, Kidd KK. HAPLO: a program using the EM algorithm to estimate the frequencies of multi-site haplotypes. J Hered. 1995 Sep-Oct;86(5):409–411. [PubMed]
  • Horai S, Kondo R, Nakagawa-Hattori Y, Hayashi S, Sonoda S, Tajima K. Peopling of the Americas, founded by four major lineages of mitochondrial DNA. Mol Biol Evol. 1993 Jan;10(1):23–47. [PubMed]
  • Itokawa M, Arinami T, Futamura N, Hamaguchi H, Toru M. A structural polymorphism of human dopamine D2 receptor, D2(Ser311-->Cys). Biochem Biophys Res Commun. 1993 Nov 15;196(3):1369–1375. [PubMed]
  • Jorde LB, Watkins WS, Carlson M, Groden J, Albertsen H, Thliveris A, Leppert M. Linkage disequilibrium predicts physical distance in the adenomatous polyposis coli region. Am J Hum Genet. 1994 May;54(5):884–898. [PMC free article] [PubMed]
  • Kidd JR, Black FL, Weiss KM, Balazs I, Kidd KK. Studies of three Amerindian populations using nuclear DNA polymorphisms. Hum Biol. 1991 Dec;63(6):775–794. [PubMed]
  • Lewontin RC. The Interaction of Selection and Linkage. I. General Considerations; Heterotic Models. Genetics. 1964 Jan;49(1):49–67. [PMC free article] [PubMed]
  • Lichter JB, Barr CL, Kennedy JL, Van Tol HH, Kidd KK, Livak KJ. A hypervariable segment in the human dopamine receptor D4 (DRD4) gene. Hum Mol Genet. 1993 Jun;2(6):767–773. [PubMed]
  • Litt M, Kramer P, Kort E, Fain P, Cox S, Root D, White R, Weissenbach J, Donis-Keller H, Gatti R, et al. The CEPH consortium linkage map of human chromosome 11. Genomics. 1995 May 1;27(1):101–112. [PubMed]
  • Mountain JL, Lin AA, Bowcock AM, Cavalli-Sforza LL. Evolution of modern humans: evidence from nuclear DNA polymorphisms. Philos Trans R Soc Lond B Biol Sci. 1992 Aug 29;337(1280):159–165. [PubMed]
  • Nevo S, Cleve H, Koller A, Eigel E, Patutschnick W, Kanaaneh H, Joel A. Serum protein polymorphisms in Arab Moslems and Druze of Israel: BF, F13B, AHSG, GC, PLG, PI, and TF. Hum Biol. 1992 Aug;64(4):587–603. [PubMed]
  • O'Hara BF, Smith SS, Bird G, Persico AM, Suarez BK, Cutting GR, Uhl GR. Dopamine D2 receptor RFLPs, haplotypes and their association with substance use in black and Caucasian research volunteers. Hum Hered. 1993 Jul-Aug;43(4):209–218. [PubMed]
  • Parsian A, Fisher L, O'Malley KL, Todd RD. A new TaqI RFLP within intron 2 of human dopamine D2 receptor gene (DRD2). Nucleic Acids Res. 1991 Dec 25;19(24):6977–6977. [PMC free article] [PubMed]
  • Sarkar G, Kapelner S, Grandy DK, Marchionni M, Civelli O, Sobell J, Heston L, Sommer SS. Direct sequencing of the dopamine D2 receptor (DRD2) in schizophrenics reveals three polymorphisms but no structural change in the receptor. Genomics. 1991 Sep;11(1):8–14. [PubMed]
  • Seeman P, Ohara K, Ulpian C, Seeman MV, Jellinger K, Van Tol HH, Niznik HB. Schizophrenia: normal sequence in the dopamine D2 receptor region that couples to G-proteins. DNA polymorphisms in D2. Neuropsychopharmacology. 1993 Feb;8(2):137–142. [PubMed]
  • Suarez BK, Parsian A, Hampe CL, Todd RD, Reich T, Cloninger CR. Linkage disequilibria at the D2 dopamine receptor locus (DRD2) in alcoholics and controls. Genomics. 1994 Jan 1;19(1):12–20. [PubMed]
  • Takahata N. Allelic genealogy and human evolution. Mol Biol Evol. 1993 Jan;10(1):2–22. [PubMed]
  • Templeton AR, Sing CF. A cladistic analysis of phenotypic associations with haplotypes inferred from restriction endonuclease mapping. IV. Nested analyses with cladogram uncertainty and recombination. Genetics. 1993 Jun;134(2):659–669. [PMC free article] [PubMed]
  • Torroni A, Schurr TG, Yang CC, Szathmary EJ, Williams RC, Schanfield MS, Troup GA, Knowler WC, Lawrence DN, Weiss KM, et al. Native American mitochondrial DNA analysis indicates that the Amerind and the Nadene populations were founded by two independent migrations. Genetics. 1992 Jan;130(1):153–162. [PMC free article] [PubMed]
  • Vigilant L, Pennington R, Harpending H, Kocher TD, Wilson AC. Mitochondrial DNA sequences in single hairs from a southern African population. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9350–9354. [PMC free article] [PubMed]
  • Watkins WS, Zenger R, O'Brien E, Nyman D, Eriksson AW, Renlund M, Jorde LB. Linkage disequilibrium patterns vary with chromosomal location: a case study from the von Willebrand factor region. Am J Hum Genet. 1994 Aug;55(2):348–355. [PMC free article] [PubMed]

Articles from American Journal of Human Genetics are provided here courtesy of American Society of Human Genetics

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • MedGen
    MedGen
    Related information in MedGen
  • Nucleotide
    Nucleotide
    Published Nucleotide sequences
  • PopSet
    PopSet
    Published population set
  • Protein
    Protein
    Published protein sequences
  • PubMed
    PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...