Exclusion of close linkage of bipolar disorder to the Gs-alpha subunit gene in nine Australian pedigrees.
Growing evidence suggests that guanine nucleotide binding proteins (G proteins) may be involved in both the pathogenesis and treatment of bipolar affective disorder. Both overactive G proteins and increased levels of the alpha subunit of the stimulatory form (Gs-alpha) have been demonstrated in peripheral leucocytes of manic patients while an increase of Gs-alpha subunit levels has also been found in a postmortem study of bipolar disorder. The function of Gs and Gi alpha subunits has now been shown to be affected by lithium. The present study aimed to determine whether bipolar affective disorder was linked to the Gs-alpha subunit gene which has been mapped to chromosomal region 20q13.2. Linkage analysis utilized the PCR amplification of a portion of the Gs-alpha gene that contains a dinucleotide repeat (CA repeat) polymorphism. Linkage of bipolar disorder and recurrent depression to the Gs-alpha subunit gene was tested using a series of autosomal dominant and recessive models with varying penetrance levels. Additionally, linkage was examined using a series of levels of definitions of affective illness. Close linkage to the Gs-alpha subunit gene was strongly excluded using each model and definition. Thus, our study indicates that a genetic defect in the Gs-alpha subunit gene is unlikely to be the cause of bipolar disorder.
Le
F
F
Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, N.S.W., Australia.
Mitchell
P
P
Vivero
C
C
Waters
B
B
Donald
J
J
Selbie
L A
LA
Shine
J
J
Schofield
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D001315:Australia; D001714:Bipolar Disorder / Q000235:genetics*; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D004274:DNA, Recombinant; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005838:Genotype; D015292:Glycoprotein Hormones, alpha Subunit / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics
D017931:DNA Primers; D004274:DNA, Recombinant; D015292:Glycoprotein Hormones, alpha Subunit