Exclusion of close linkage of bipolar disorder to the dopamine D3 receptor gene in nine Australian pedigrees.
The recently cloned dopamine D3 receptor (DRD3) gene is of potential relevance to the aetiology of bipolar disorder because of an almost exclusive expression in limbic tissue, the region of the brain putatively responsible for control of emotion. We therefore aimed to determine whether bipolar disorder in nine pedigrees (with 171 members) was linked to this receptor gene, which has been mapped to chromosomal region 3q 13.3. Linkage of bipolar disorder and recurrent depression to the DRD3 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 (ranging from bipolar I alone to all affective disorders). Close linkage to the DRD3 gene was strongly excluded using each model and definition, and these conclusions persisted when a wide range of rates of 'sporadic' (non-genetic) presentations of illness were incorporated in the analysis.
Mitchell
P
P
School of Psychiatry, University of New South Wales, Sydney, Australia.
Waters
B
B
Vivero
C
C
Le
F
F
Donald
J
J
Tully
M
M
Campedelli
K
K
Lannfelt
L
L
Sokoloff
P
P
Shine
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D002869:Chromosome Aberrations / Q000235:genetics; D025063:Chromosome Disorders; D002893:Chromosomes, Human, Pair 3; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D010375:Pedigree; D011954:Receptors, Dopamine / Q000235:genetics*; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3
C493593:DRD3 protein, human; D005819:Genetic Markers; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3