SYSTEMATIC SCREENING FOR MUTATIONS IN THE PROMOTER AND THE CODING REGION OF THE 5-HT1A GENE

被引:57
作者
ERDMANN, J
SHIMRONABARBANELL, D
CICHON, S
ALBUS, M
MAIER, W
LICHTERMANN, D
MINGES, J
REUNER, U
FRANZEK, E
ERTL, MA
HEBEBRAND, J
REMSCHMIDT, H
LEHMKUHL, G
POUSTKA, F
SCHMIDT, M
FIMMERS, R
KORNER, J
RIETSCHEL, M
PROPPING, P
NOTHEN, MM
机构
[1] UNIV BONN,INST HUMAN GENET,D-53111 BONN,GERMANY
[2] UNIV BONN,INST MED STAT,D-53111 BONN,GERMANY
[3] UNIV BONN,DEPT PSYCHIAT,D-53111 BONN,GERMANY
[4] MENTAL STATE HOSP,HAAR,GERMANY
[5] UNIV MAINZ,DEPT PSYCHIAT,W-6500 MAINZ,GERMANY
[6] MED ACAD CARL GUSTAV CARUS,DEPT PSYCHIAT,DRESDEN,GERMANY
[7] UNIV WURZBURG,DEPT PSYCHIAT,W-8700 WURZBURG,GERMANY
[8] UNIV MUNICH,DEPT PSYCHIAT,W-8000 MUNICH,GERMANY
[9] UNIV MARBURG,DEPT CHILD & ADOLESCENT PSYCHIAT,W-3550 MARBURG,GERMANY
[10] UNIV COLOGNE,DEPT CHILD & ADOLESCENT PSYCHIAT,W-5000 COLOGNE,GERMANY
[11] UNIV FRANKFURT,DEPT CHILD & ADOLESCENT PSYCHIAT,W-6000 FRANKFURT,GERMANY
[12] ZENT INST SEEL GESUNDHEIT,DEPT CHILD & ADOLESCENT PSYCHIAT,W-6800 MANNHEIM,GERMANY
来源
AMERICAN JOURNAL OF MEDICAL GENETICS | 1995年 / 60卷 / 05期
关键词
SEROTONIN RECEPTOR 5-HT1A; SINGLE-STRAND CONFORMATION ANALYSIS; BIPOLAR AFFECTIVE DISORDER; SCHIZOPHRENIA; TOURETTES SYNDROME;
D O I
10.1002/ajmg.1320600509
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
In the present study we sought to identify genetic variation in the 5-HT1A receptor gene which through alteration of protein function or level of expression might contribute to the genetic predisposition to neuropsychiatric diseases. Genomic DNA sam ples from 159 unrelated subjects (including 45 schizophrenic, 46 bipolar affective, and 43 patients with Tourette's syndrome, as well as 25 healthy controls) were investigated by single-strand conformation analysis. Overlapping PCR (polymerase chain reaction) fragments covered the whole coding sequence as well as the 5' untranslated region of the 5-HT1A gene. The region upstream to the coding sequence we investigated contains a functional promoter. We found two rare nucleotide sequence variants. Both mutations are located in the coding region of the gene: a coding mutation (A-->G) in nucleotide position 82 which leads to an amino acid exchange (Ile-->Val) in position 28 of the receptor protein and a silent mutation (C-->T) in nucleotide position 549. The occurrence of the Ile-28-Val substitution was studied in an extended sample of patients (n = 352) and controls (n = 210) but was found in similar frequencies in all groups. Thus, this mutation is unlikely to play a significant role in the genetic predisposition to the diseases investigated. In conclusion, our study does not provide evidence that the 5-HT1A gene plays either a major or a minor role in the genetic predisposition to schizophrenia, bipolar affective disorder, or Tourette's syndrome. (C) 1995 Wiley-Liss, Inc.
引用
收藏
页码:393 / 399
页数:7
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