Human G(olf) gene polymorphisms and vulnerability to bipolar disorder.
Two intronic polymorphisms of the human alpha subunit of the olfactory G-protein (G(olf)) are described. They were detected with single-stranded conformational polymorphism (SSCP) methods and confirmed by sequencing both strands. These single base pair (bp) substitutions occur in introns 3 (an A/G at 35 bp 3' from the exon 3/intron 3 5' splice site) and 10 (an T/G at 7 bp 5' from the 3' splice site). Both polymorphisms are relatively common, with minor allele frequencies of 31% (intron 3) and 16% (intron 10). The intron 3 variant shows no linkage disequilibrium with an intron 5 (CA)n microsatellite located approximately 50 kb 3' from the intron 3 variant, among a small group of German individuals with schizophrenia. The intron 3 variant is interesting because it may create an 'in-frame' cryptic splice site which, if activated, would add 12 residues to exon 3. The intron 10 variant is interesting because a purine is substituted for a pyrimidine in the 'polypyrimidine' tract of the 3' splice site, a single base substitution of the type which has been associated with aberrant splicing in the androgen receptor gene.
Berrettini
W H
WH
Department of Psychiatry, University of Pennsylvania, Philadelphia 19104, USA. wadeb@mail.med.upenn.edu
Vuoristo
J
J
Ferraro
T N
TN
Buono
R J
RJ
Wildenauer
D
D
Ala-Kokko
L
L
D000483:Alleles; D001714:Bipolar Disorder / Q000453:epidemiology / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D044385:GTP-Binding Protein alpha Subunits; D019204:GTP-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005858:Germany / Q000453:epidemiology; D020962:Heterotrimeric GTP-Binding Proteins; D006801:Humans; D007438:Introns / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D017354:Point Mutation; D018807:Polymorphism, Single-Stranded Conformational; D012326:RNA Splicing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics
D044385:GTP-Binding Protein alpha Subunits; D009419:Nerve Tissue Proteins; C084618:olfactory G protein subunit alpha olf; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins