Serotonin transporter evolution and impact of polymorphic transcriptional regulation
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Serotonin transporter evolution and impact of polymorphic transcriptional regulation. / Søeby, Karen; Larsen, Svend Ask; Olsen, Line; Rasmussen, Henrik B; Werge, Thomas.
I: American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics, Bind 136B, Nr. 1, 2005, s. 53-7.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Serotonin transporter evolution and impact of polymorphic transcriptional regulation
AU - Søeby, Karen
AU - Larsen, Svend Ask
AU - Olsen, Line
AU - Rasmussen, Henrik B
AU - Werge, Thomas
N1 - Copyright 2005 Wiley-Liss, Inc.
PY - 2005
Y1 - 2005
N2 - The serotonin transporter (SERT) is the primary drug target in the current antidepressant therapy. A functional polymorphism in the 2nd intron of the 5HTT gene encoding the SERT has been identified and associated with susceptibility to affective disorders and treatment response to antidepressants. This study addresses the possible impact of the variable number of tandem repeats (VNTR) to behavior and disease by examining the evolutionary origin and mechanisms of differential transcriptional regulation of SERT. We trace the evolutionary origin of the VNTR and show that it is present and varies extensively across the great apes and monkeys as well as in rodents while it is absent in non-mammals. As in humans, the VNTR sequence may be polymorphic within species and thus it may underlie both inter- and intraspecies differences. Also, we find new putative binding sites for several transcription factors in the VNTRs of all mammalian SERT genes. The number of these putative binding sites varies proportionally to the length of the VNTR. We propose that the intronic VNTR have been selectively targeted through mammalian evolution to finetune transcriptional regulation of the serotonin expression.
AB - The serotonin transporter (SERT) is the primary drug target in the current antidepressant therapy. A functional polymorphism in the 2nd intron of the 5HTT gene encoding the SERT has been identified and associated with susceptibility to affective disorders and treatment response to antidepressants. This study addresses the possible impact of the variable number of tandem repeats (VNTR) to behavior and disease by examining the evolutionary origin and mechanisms of differential transcriptional regulation of SERT. We trace the evolutionary origin of the VNTR and show that it is present and varies extensively across the great apes and monkeys as well as in rodents while it is absent in non-mammals. As in humans, the VNTR sequence may be polymorphic within species and thus it may underlie both inter- and intraspecies differences. Also, we find new putative binding sites for several transcription factors in the VNTRs of all mammalian SERT genes. The number of these putative binding sites varies proportionally to the length of the VNTR. We propose that the intronic VNTR have been selectively targeted through mammalian evolution to finetune transcriptional regulation of the serotonin expression.
U2 - http://dx.doi.org/10.1002/ajmg.b.30184
DO - http://dx.doi.org/10.1002/ajmg.b.30184
M3 - Journal article
VL - 136B
SP - 53
EP - 57
JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
SN - 1552-4841
IS - 1
ER -
ID: 48581709