ABSTRACT
OBJECTIVE: In 1986 and 1987, Cloninger postulated the existence of the heritable behavioral trait of novelty seeking and its putative underpinnings in the dopaminergic systems of the ventral midbrain. Two widely reported studies found significant associations between novelty seeking and the type 4 dopamine receptor gene (DRD4), although a more recent study did not. The authors' objective was to investigate this association in two New Zealand samples. METHOD: The authors studied two nonoverlapping samples: subjects in a depression treatment trial (N = 86) and subjects from 14 pedigrees dense with alcoholism (N = 181). DRD4 genotyping was based on a standard protocol. RESULTS: Novelty seeking and DRD4 were not statistically associated. CONCLUSIONS: In these samples, there was no suggestion that the DRD4 polymorphism contributed to individual differences in the behavioral trait of novelty seeking.
Subject(s)
Exploratory Behavior/physiology , Mesencephalon/physiology , Receptors, Dopamine D2/genetics , Adult , Alcoholism/diagnosis , Alcoholism/genetics , Alcoholism/psychology , Alleles , Depressive Disorder/diagnosis , Depressive Disorder/genetics , Depressive Disorder/psychology , Female , Humans , Male , New Zealand , Personality/genetics , Personality Inventory , Polymorphism, Genetic , Receptors, Dopamine D2/physiology , Receptors, Dopamine D4Subject(s)
Carrier Proteins/genetics , Exploratory Behavior/physiology , Membrane Glycoproteins , Membrane Transport Proteins , Nerve Tissue Proteins/genetics , Polymorphism, Genetic , Adult , Alleles , DNA/analysis , Depressive Disorder/drug therapy , Depressive Disorder/genetics , Depressive Disorder/psychology , Dopamine Plasma Membrane Transport Proteins , Double-Blind Method , Female , Genetic Markers , Genotype , Humans , Male , PedigreeABSTRACT
X-linked adrenoleukodystrophy (ALD) is a degenerative neurological disease characterized by the accumulation of very long chain fatty acids in various tissues and demyelination of the central nervous system. The human gene responsible for the disease encodes a membrane-bound ATP-binding transporter protein that is located in peroxisomes. We isolated the mouse adrenoleukodystrophy gene, determined its structure, and mapped it both cytogenetically and genetically. The mouse gene is very similar in structure to the human gene, consisting of 10 exons arranged over a 22-kb genomic region. We localized it in band B of the mouse X chromosome by fluorescence in situ hybridization analysis and, using a new microsatellite repeat polymorphism, determined the map location as 47 cM from the X centromere. We found evidence for other sequences in the mouse genome related to the 3' end of Aldgh. This study paves the way for the construction of gene-targeting plasmids that may be used to develop an animal model of ALD.
