Presence of multiple functional polyadenylation signals and a single nucleotide polymorphism in the 3 ' untranslated region of the human serotonin transporter gene

The human serotonin transporter (hSERT) gene is a candidate for involvement in the aetiology of affective disorders. In humans, multiple transcripts o f the gene have been detected by northern blot analysis of brain and other tissues. We performed 3' rapid amplification of cDNA ends to identify the c ommon sites of polyadenylation in hSERT mRNA from human JAR cells and whole blood. Two major polyadenylation sites were identified: one 567 bp downstr eam of the stop codon, consistent with the usage of the polyadenylation sig nal AATGAA, and a second site 690 bp downstream of the stop codon. The puta tive polyadenylation signal upstream of this site contained a single nucleo tide polymorphism (AG/TTAAC). However, allelic Variation at this site did n ot influence polyadenylation site usage, and there were no significant diff erences in the abundance of the two alleles of this polymorphism between 32 9 control subjects, 158 individuals with major depression, and 130 individu als with bipolar affective disorder. This single nucleotide polymorphism in the 3' untranslated region of the hSERT gene should provide a useful genet ic marker in the evaluation of hSERT as a candidate gene influencing suscep tibility to mood disorders.