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

Journal Article · Tue Jun 01 04:00:00 EDT 1993 · American Journal of Human Genetics; (United States)

OSTI ID:6441800

Coon, H; Jensen, S; Hoff, M; Holik, J; Plaetke, R; Reimherr, F; Wender, P; Leppert, M; Byerley, W ^[1]

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1. Univ. of Utah, Salt Lake City (United States)

Manic-depressive illness (MDI), also known as [open quotes]bipolar affective disorder[close quotes], 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, the authors ascertained eight moderately sized pedigrees containing multiple cases of the disease. For a four-allele marker mapping at 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 <[minus]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, the linkage results should be interpreted as preliminary data, as 68 unaffected individuals are not past the age of risk. 72 refs., 2 tabs.

• OSTI ID: 6441800
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 52:6; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
ADRENAL HORMONES
AMINES
AMINO ACIDS
AMINOBUTYRIC ACID
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL INDICATORS
CARBOXYLIC ACIDS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CHROMOSOMES
DOPAMINE
DRUGS
GENETIC MAPPING
GLUTAMIC ACID
HORMONES
HUMAN CHROMOSOME 5
HUMAN CHROMOSOMES
HYDROXY COMPOUNDS
MAPPING
MEMBRANE PROTEINS
MENTAL DISORDERS
NEUROREGULATORS
NORADRENALINE
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHENOLS
POLYPHENOLS
PROTEINS
RECEPTORS
SYMPATHOMIMETICS