A HYPERVARIABLE SEGMENT IN THE HUMAN DOPAMINE RECEPTOR D(4) (DRD4) GENE

被引：515

作者：

LICHTER, JB

BARR, CL

KENNEDY, JL

VANTOL, HHM

KIDD, KK

LIVAK, KJ

机构：

[1] DUPONT MERCK PHARMACEUT CO,EXPTL STN,POB 80328,WILMINGTON,DE 19880

[2] UNIV TORONTO,CLARKE INST PSYCHIAT,NEUROGENET & NEUROBIOL LAB,NEUROGENET SECT,TORONTO M5T 1R8,ONTARIO,CANADA

[3] YALE UNIV,SCH MED,DEPT GENET,NEW HAVEN,CT 06510

来源：

HUMAN MOLECULAR GENETICS | 1993年 / 2卷 / 06期

关键词：

D O I：

10.1093/hmg/2.6.767

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The human dopamine D4 receptor contains a novel polymorphism within the putative third cytoplasmic loop of the protein. The polymorphism is characterized by a varying number of direct imperfect 48-bp repeats in the gene. Pharmacological characterization has suggested that this receptor is the site through which the atypical neuroleptic clozapine exerts its antipsychotic action and that some polymorphic variants display different pharmacological properties. Further analysis of the repeat region using innovative technologies indicates that the alleles vary not only in the number of repeats (2-8 or 10 repeat units) but also in the sequence of the repeats and the order in which they appear. In 178 unrelated chromosomes we have identified 19 different repeats in 25 different haplotypes coding for 18 different predicted amino acid sequences, making this one of the most variable functional proteins currently described.

引用

页码：767 / 773

页数：7

共 18 条

[1]

Bowcock A M, 1987, Gene Geogr, V1, P47

[2] PROGRAM DESCRIPTION - CENTER-DETUDE-DU-POLYMORPHISME-HUMAIN (CEPH) - COLLABORATIVE GENETIC-MAPPING OF THE HUMAN GENOME [J].

DAUSSET, J ;

CANN, H ;

COHEN, D ;

LATHROP, M ;

LALOUEL, JM ;

WHITE, R .

GENOMICS, 1990, 6 (03) :575-577

[3] THE D4 DOPAMINE RECEPTOR (DRD4) MAPS TO DISTAL-11P CLOSE TO HRAS [J].

GELERNTER, J ;

KENNEDY, JL ;

VANTOL, HHM ;

CIVELLI, O ;

KIDD, KK .

GENOMICS, 1992, 13 (01) :208-210

[4]

GRANDY DK, 1990, AM J HUM GENET, V47, P828

[5]

GRANDY DK, 1989, AM J HUM GENET, V45, P778

[6] DIRECT SOLID-PHASE SEQUENCING OF GENOMIC AND PLASMID DNA USING MAGNETIC BEADS AS SOLID SUPPORT [J].

HULTMAN, T ;

STAHL, S ;

HORNES, E ;

UHLEN, M .

NUCLEIC ACIDS RESEARCH, 1989, 17 (13) :4937-4946

[7] MINISATELLITE REPEAT CODING AS A DIGITAL APPROACH TO DNA TYPING [J].

JEFFREYS, AJ ;

MACLEOD, A ;

TAMAKI, K ;

NEIL, DL ;

MONCKTON, DG .

NATURE, 1991, 354 (6350) :204-209

[8]

KANE J, 1988, ARCH GEN PSYCHIAT, V45, P789

[9]

KENNEDY JL, 1991, NUCLEIC ACIDS RES, V19, P5805

[10]

KIDD JR, 1991, HUM BIOL, V63, P775

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