Possible locus for bipolar disorder near the dopamine transporter on chromosome 5

American Journal of Medical Genetics
J R KelsoeR A Remick

Abstract

The dopamine transporter (DAT) plays a key role in the regulation of dopaminergic neurotransmission by mediating the active reuptake of synaptic dopamine. It is an important candidate gene for bipolar disorder because of data implicating dopamine abnormalities in mania, and because it is the site of action of amphetamine, which has activating and psychotogenic properties. DAT has recently been cloned by its homology to a family of transporters, and mapped to chromosome 5p15.3. We tested DAT for linkage to bipolar disorder in a collection of 21 families from the general North American population (University of California, San Diego/University of British Columbia [UCSD/UBC] families), three Icelandic pedigrees, and Old Order Amish pedigree 110. We examined three markers at DAT, including a 5' TaqI RFLP (HDAT-TaqI), a highly polymorphic variable number of tandem repeats marker (VNTR) (HDAT-VNTR1), and a 3' 40-bp repeat marker (HDAT-PCR1), as well as two nearby microsatellite markers, D5S392 and D5S406. A maximum lod score of 2.38 was obtained at D5S392 in one of the UCSD/UBC families under an autosomal-dominant model. A lod score of 1.09 was also obtained under the same dominant model in the Amish at HDAT-PCR1. In the combined set...Continue Reading

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