A genome-wide search for genes predisposing to manic-depression, assuming autosomal dominant inheritance

• Published in: American journal of human genetics 1993-06, Vol.52 (6), p.1234-1249
• Main Authors: COON, H, JENSEN, S, HOFF, M, HOLIK, J, PAETKE, R, REIMHERR, F, WENDER, P, LEPPERT, M, BYERLEY, W
• Format: Article
• Language: English
• Subjects: ADRENAL HORMONES; Adult; Adult and adolescent clinical studies; AMINES; AMINO ACIDS; AMINOBUTYRIC ACID; AROMATICS; AUTONOMIC NERVOUS SYSTEM AGENTS; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; BIOLOGICAL INDICATORS; Bipolar Disorder - genetics; CARBOXYLIC ACIDS; CARDIOTONICS; CARDIOVASCULAR AGENTS; Chromosome Mapping; CHROMOSOMES; Depression; DNA; DOPAMINE; DRUGS; Genes, Dominant; Genetic Linkage; GENETIC MAPPING; Genetic Markers; Genome, Human; Genotype; genotypes; GLUTAMIC ACID; HORMONES; HUMAN CHROMOSOME 5; HUMAN CHROMOSOMES; Humans; HYDROXY COMPOUNDS; inheritance; linkage analysis; Lod Score; man; manic depression; MAPPING; Medical sciences; MEMBRANE PROTEINS; MENTAL DISORDERS; Mood disorders; NEUROREGULATORS; NORADRENALINE; ORGANIC ACIDS; ORGANIC COMPOUNDS; Pedigree; PHENOLS; POLYPHENOLS; PROTEINS; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; RECEPTORS; SYMPATHOMIMETICS 550400 > Genetics
• ISSN: 0002-9297; 1537-6605

Manic-depressive illness (MDI), also known as "bipolar affective disorder," is a common and devastating neuropsychiatric illness. Although pivotal biochemical alterations underlying the disease are unknown, results of family, twin, and adoption studies consistently implicate genetic transmission in the pathogenesis of MDI. In order to carry out linkage analysis, we ascertained eight moderately sized pedigrees containing multiple cases of the disease. For a four-allele marker mapping 5 cM from the disease gene, the pedigree sample has > 97% power to detect a dominant allele under genetic homogeneity and has > 73% power under 20% heterogeneity. To date, the eight pedigrees have been genotyped with 328 polymorphic DNA loci throughout the genome. When autosomal dominant inheritance was assumed, 273 DNA markers gave lod scores < -2.0 at recombination fraction (theta) = .0, 174 DNA loci produced lod scores < -2.0 at theta = .05, and 4 DNA marker loci yielded lod scores > 1 (chromosome 5--D5S39, D5S43, and D5S62; chromosome 11--D11S85). Of the markers giving lod scores > 1, only D5S62 continued to show evidence for linkage when the affected-pedigree-member method was used. The D5S62 locus maps to distal 5q, a region containing neurotransmitter-receptor genes for dopamine, norepinephrine, glutamate, and gamma-aminobutyric acid. Although additional work in this region may be warranted, our linkage results should be interpreted as preliminary data, as 68 unaffected individuals are not past the age of risk.