Linkage mapping of serotonin transporter protein gene SLC6A4 on chromosome 17

Abnormalities in monoamine metabolism, including serotonin metabolism, have been implicated in the pathophysiology of affective disorders, schizophrenia, suicide, and other psychiatric disorders. Serotonin transporter protein (SERT) allows neurons to retrieve serotonin that has been released into a synapse. SERT is a site of action for several drugs with CMS effects, including both therapeutic agents (e.g., antidepressants) and drugs of abuse (e.g., cocaine). This gene had previously been physically mapped to chromosome 17. We used a PCR product corresponding to the 3 untranslated region of the gene as a probe to identify restriction fragment length polymorphism (RFLP), which we then used to establish that the SLC6A4, genetic locus for SERT, is near 17q12 and probably flanked by D17S58 and D17S73 (a location consistent with observed crossovers). These data should be useful for linkage studies of neuropsychiatric disorders. (Joyce et al. 1993). Neurotransmitter reuptake sites (including also the norepinephrine transporter protein and the dopamine transporter protein) are logical candidate genes for susceptibility to psychiatric illness. We have previously (Gelernter et al. 1993) mapped the norepinephrine transporter protein to chromosome 16q21. We describe here linkage mapping of the serotonin transporter protein gene (gene symbol SLC6A4, for solute carrier family 6 (neurotransporter, serotonin), member 4), which was cloned in 1991 (Blakely et al. 1991; Hoffman et al. 1991) and previously assigned to chromosome 17, most likely to band 17q11.2, by in situ hybridization (Ramamoorthy et al. 1993). Our linkage results confirm the initial mapping of SLC6A4 and place it in the linkage map of proximal 17q.