Presence of Multiple Functional Polyadenylation Signals and a Single Nucleotide Polymorphism in the 3′ Untranslated Region of the Human Serotonin Transporter Gene

Authors

  • Sharon Battersby,

    1. MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Edinburgh, Scotland*University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh, ScotlandMRC Human Genetics Unit, Western General Hospital, Edinburgh, ScotlandUniversity Department of Psychiatry, Warneford Hospital, Oxford, England
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  • Alan D. Ogilvie,

    1. MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Edinburgh, Scotland*University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh, ScotlandMRC Human Genetics Unit, Western General Hospital, Edinburgh, ScotlandUniversity Department of Psychiatry, Warneford Hospital, Oxford, England
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  • Douglas H. R. Blackwood,

    1. MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Edinburgh, Scotland*University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh, ScotlandMRC Human Genetics Unit, Western General Hospital, Edinburgh, ScotlandUniversity Department of Psychiatry, Warneford Hospital, Oxford, England
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  • * Sanbing Shen,

    1. MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Edinburgh, Scotland*University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh, ScotlandMRC Human Genetics Unit, Western General Hospital, Edinburgh, ScotlandUniversity Department of Psychiatry, Warneford Hospital, Oxford, England
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  • Miratul M. K. Muqit,

    1. MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Edinburgh, Scotland*University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh, ScotlandMRC Human Genetics Unit, Western General Hospital, Edinburgh, ScotlandUniversity Department of Psychiatry, Warneford Hospital, Oxford, England
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  • Walter J. Muir,

    1. MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Edinburgh, Scotland*University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh, ScotlandMRC Human Genetics Unit, Western General Hospital, Edinburgh, ScotlandUniversity Department of Psychiatry, Warneford Hospital, Oxford, England
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  • * Peter Teague,

    1. MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Edinburgh, Scotland*University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh, ScotlandMRC Human Genetics Unit, Western General Hospital, Edinburgh, ScotlandUniversity Department of Psychiatry, Warneford Hospital, Oxford, England
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  • Guy M. Goodwin,

    1. MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Edinburgh, Scotland*University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh, ScotlandMRC Human Genetics Unit, Western General Hospital, Edinburgh, ScotlandUniversity Department of Psychiatry, Warneford Hospital, Oxford, England
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  • Anthony J. Harmar

    1. MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Edinburgh, Scotland*University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh, ScotlandMRC Human Genetics Unit, Western General Hospital, Edinburgh, ScotlandUniversity Department of Psychiatry, Warneford Hospital, Oxford, England
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  • Lippincott Williams & Wilkins, Inc., Philadelphia

  • Abbreviations used: AUAP, abridged universal amplification primer; DEPC, diethyl pyrocarbonate; hSERT, human serotonin transporter; RACE, rapid amplification of cDNA ends; UTRF, untranslated region forward.

Address correspondence and reprint requests to Dr. S. Battersby at MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Morningside Park, Edinburgh, EH10 5HF, U.K.

Abstract

Abstract: The human serotonin transporter (hSERT) gene is a candidate for involvement in the aetiology of affective disorders. In humans, multiple transcripts of 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 common sites of polyadenylation in hSERT mRNA from human JAR cells and whole blood. Two major polyadenylation sites were identified: one 567 bp downstream of the stop codon, consistent with the usage of the polyadenylation signal AATGAA, and a second site 690 bp downstream of the stop codon. The putative polyadenylation signal upstream of this site contained a single nucleotide polymorphism (AG/TTAAC). However, allelic variation at this site did not influence polyadenylation site usage, and there were no significant differences in the abundance of the two alleles of this polymorphism between 329 control subjects, 158 individuals with major depression, and 130 individuals with bipolar affective disorder. This single nucleotide polymorphism in the 3′ untranslated region of the hSERT gene should provide a useful genetic marker in the evaluation of hSERT as a candidate gene influencing susceptibility to mood disorders.

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