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Title: Systematic screening for mutations in the human serotonin 1F receptor gene in patients with bipolar affective disorder and schizophrenia

Abstract

Using single strand conformational analysis we screened the complete coding sequence of the serotonin 1F (5-HT{sub 1F}) receptor gene for the presence of DNA sequence variation in a sample of 137 unrelated individuals including 45 schizophrenic patients, 46 bipolar patients, as well as 46 healthy controls. We detected only three rare sequence variants which are characterized by single base pair substitutions, namely a silent T{r_arrow}A transversion in the third position of codon 261 (encoding isoleucine), a silent C{r_arrow}T transition in the third position of codon 176 (encoding histidine), and a C{r_arrow}T transition in position -78 upstream from the start codon. The lack of significant mutations in patients suffering from schizophrenia and bipolar affective disorder indicates that the 5-HT{sub 1F} receptor is not commonly involved in the etiology of these diseases. 12 refs., 1 fig., 2 tabs.

Authors:
; ; ; ;  [1]
  1. Univ. of Bonn (Germany) [and others
Publication Date:
OSTI Identifier:
447666
Resource Type:
Journal Article
Resource Relation:
Journal Name: American Journal of Medical Genetics; Journal Volume: 67; Journal Issue: 2; Other Information: PBD: 9 Apr 1996
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; NERVOUS SYSTEM DISEASES; ETIOLOGY; PATIENTS; MENTAL DISORDERS; HEREDITARY DISEASES; SEROTONIN; RECEPTORS; GENETIC MAPPING; GENE MUTATIONS; DNA SEQUENCING; SCREENING; NUCLEOTIDES; POLYMERASE CHAIN REACTION

Citation Formats

Shimron-Abarbanell, D., Harms, H., Erdmann, J., Propping, P., and Noethen, M.M.. Systematic screening for mutations in the human serotonin 1F receptor gene in patients with bipolar affective disorder and schizophrenia. United States: N. p., 1996. Web. doi:10.1002/(SICI)1096-8628(19960409)67:2<225::AID-AJMG16>3.0.CO;2-L.
Shimron-Abarbanell, D., Harms, H., Erdmann, J., Propping, P., & Noethen, M.M.. Systematic screening for mutations in the human serotonin 1F receptor gene in patients with bipolar affective disorder and schizophrenia. United States. doi:10.1002/(SICI)1096-8628(19960409)67:2<225::AID-AJMG16>3.0.CO;2-L.
Shimron-Abarbanell, D., Harms, H., Erdmann, J., Propping, P., and Noethen, M.M.. 1996. "Systematic screening for mutations in the human serotonin 1F receptor gene in patients with bipolar affective disorder and schizophrenia". United States. doi:10.1002/(SICI)1096-8628(19960409)67:2<225::AID-AJMG16>3.0.CO;2-L.
@article{osti_447666,
title = {Systematic screening for mutations in the human serotonin 1F receptor gene in patients with bipolar affective disorder and schizophrenia},
author = {Shimron-Abarbanell, D. and Harms, H. and Erdmann, J. and Propping, P. and Noethen, M.M.},
abstractNote = {Using single strand conformational analysis we screened the complete coding sequence of the serotonin 1F (5-HT{sub 1F}) receptor gene for the presence of DNA sequence variation in a sample of 137 unrelated individuals including 45 schizophrenic patients, 46 bipolar patients, as well as 46 healthy controls. We detected only three rare sequence variants which are characterized by single base pair substitutions, namely a silent T{r_arrow}A transversion in the third position of codon 261 (encoding isoleucine), a silent C{r_arrow}T transition in the third position of codon 176 (encoding histidine), and a C{r_arrow}T transition in position -78 upstream from the start codon. The lack of significant mutations in patients suffering from schizophrenia and bipolar affective disorder indicates that the 5-HT{sub 1F} receptor is not commonly involved in the etiology of these diseases. 12 refs., 1 fig., 2 tabs.},
doi = {10.1002/(SICI)1096-8628(19960409)67:2<225::AID-AJMG16>3.0.CO;2-L},
journal = {American Journal of Medical Genetics},
number = 2,
volume = 67,
place = {United States},
year = 1996,
month = 4
}
  • A possible dysregulation of dopaminergic neurotransmission has been implicated in a variety of neuropsychiatric diseases. In the present study we systematically searched for the presence of mutations in the 5{prime}-flanking region of the dopamine D{sub 1} receptor (DRD1) gene. This region has previously been shown to contain a functional promoter. We investigated 119 unrelated individuals (including 36 schizophrenic patients, 38 bipolar affective patients, and 45 healthy controls) using single-strand conformation analysis (SSCA). Eleven overlapping PCR fragments covered 2,189 bp of DNA sequence. We identified six single base substitutions: -2218T/C, -2102C/A, -2030T/C, -1992G/A, -1251G/C, and -800T/C. None of the mutations wasmore » found to be located in regions which have important influence on the level of transcriptional activity. Allele frequencies were similar in patients and controls, indicating that genetic variation in the 5{prime}-regulatory region of the DRD1 gene is unlikely to play a frequent, major role in the genetic predisposition to either schizophrenia or bipolar affective disorder. 31 refs., 3 tabs.« less
  • A new class of disease (including Huntington disease, Kennedy disease, and spinocerebellar ataxias types 1 and 3) results from abnormal expansions of CAG trinucleotides in the coding regions of genes. In all of these diseases the CAG repeats are thought to be translated into polyglutamine tracts. There is accumulating evidence arguing for CAG trinucleotide expansions as one of the causative disease mutations in schizophrenia and bipolar affective disorder. We and others believe that the TATA-binding protein (TBP) is an important candidate to investigate in these diseases as it contains a highly polymorphic stretch of glutamine codons, which are close tomore » the threshold length where the polyglutamine tracts start to be associated with disease. Thus, we examined the lengths of this polyglutamine repeat in normal unrelated East Anglians, South African Blacks, sub-Saharan Africans mainly from Nigeria, and Asian Indians. We also examined 43 bipolar affective disorder patients and 65 schizophrenic patients. The range of polyglutamine tract-lengths that we found in humans was from 26-42 codons. No patients with bipolar affective disorder and schizophrenia had abnormal expansions at this locus. 22 refs., 1 tab.« less
  • A variety of studies have reported possible genetic associations between bipolar affective disorder and different loci using relative risk approaches. An alternative approach is to determine untransmitted genotypes from families selected through a single affected individual. We have used both approaches to test for possible associations between alleles of the dopamine D3 receptor gene and bipolar affective disorder. For relative risk studies, the probands of multiple incidence bipolar affective disorder (n=66) and alcoholism (n=132) families and psychiatric normal controls (n=91) have been compared. Non-transmitted allele approaches have used bipolar affective disorder (n=28) and alcoholic (n=25) probands in which both parentsmore » were available for genotyping. Using the Bal I restriction enzyme site polymorphism of Lannfelt, we have found no differences in the allele or genotype frequencies for bipolar or alcoholic probands versus psychiatrically normal controls. In contrast, we have found evidence for an increased frequency of allele 1 and allele 1 containing genotypes in transmitted alleles from bipolar families.« less
  • A variety of studies have reported possible genetic associations between bipolar affective disorder and different loci using relative risk (case-control) comparisons. An alternative approach is to construct a contrast group using parental alleles which were not transmitted to an affected individual. We have used both approaches to test for possible associations between alleles of the dopamine D{sub 3} receptor gene and bipolar affective disorder. For relative risk studies, the probands of multiple incidence bipolar affective disorder families have been compared to alcoholic and psychiatrically normal contrast groups. Nontransmitted allele approaches have used bipolar affective disorder and alcoholic probands in whichmore » both parents were available for genotyping. Using the BalI restriction enzyme site polymorphism of Lannfelt et al., we have found no differences in the allele or genotype frequencies for bipolar vs. alcoholic or psychiatrically normal controls. In contrast, we have found evidence for an increased frequency of allele 1 and allele 1 containing genotypes in transmitted alleles from bipolar families. 21 refs., 4 tabs.« less
  • A group of diseases are due to abnormal expansions of trinucleotide repeats. These diseases all affect the nervous system. In addition, they manifest the phenomenon of anticipation, in which the disease tends to present at an earlier age or with greater severity in successive generations. Many additional genes with trinucleotide repeats are believed to be expressed in the human brain. As anticipation has been reported in schizophrenia and bipolar affective disorder, we have examined allele distributions of 13 trinucleotide repeat-containing genes, many novel and all expressed in the brain, in genomic DNA from schizophrenic (n = 20-97) and bipolar affectivemore » disorder patients (23-30) and controls (n = 43-146). No evidence was obtained to implicate expanded alleles in these 13 genes as causal factors in these diseases. 26 refs., 1 fig., 2 tabs.« less