A genome-wide search for genes predisposing to manic-depression, assuming autosomal dominant inheritance
- 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), Vol. 52:6; ISSN 0002-9297
- Country of Publication:
- United States
- Language:
- English
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HUMAN CHROMOSOME 5
GENETIC MAPPING
MENTAL DISORDERS
BIOLOGICAL INDICATORS
AMINOBUTYRIC ACID
DOPAMINE
GLUTAMIC ACID
HUMAN CHROMOSOMES
NEUROREGULATORS
NORADRENALINE
RECEPTORS
ADRENAL HORMONES
AMINES
AMINO ACIDS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
CARBOXYLIC ACIDS
CARDIOTONICS
CARDIOVASCULAR AGENTS
CHROMOSOMES
DRUGS
HORMONES
HYDROXY COMPOUNDS
MAPPING
MEMBRANE PROTEINS
ORGANIC ACIDS
ORGANIC COMPOUNDS
PHENOLS
POLYPHENOLS
PROTEINS
SYMPATHOMIMETICS
550400* - Genetics