Figure 1.

Occurrence, cross-species conservation, and functional assessment of disease-associated coding DAT variants. A, schematic representation of DAT illustrating the position of six coding DAT variants, identified in patients with psychiatric disease. B, for each coding variant the table lists the following: index patient's diagnosis; cross-species sequence conservation of the affected residues; the variant's reported frequencies in reference databases; and the mutations predicted probability of having damaging impact on DAT function from PolyPhen-2 scores. C, direct functional evaluation of [³H]dopamine saturation uptake with indicated dopamine concentrations into transiently transfected COS-7 cells. Dopamine uptake curves are presented as average curves (mean ± S.E.) of three experiments, each performed in triplicate and normalized to the fitted V_max of DAT WT. BP, bipolar disorder; EOP, early-onset parkinsonism; MAF, minor allele frequency.