title: Mosaicism for a serotonin transporter gene promoter-associated deletion: decreased recombination in depression.
abstract: Transcriptional activity of the human serotonin transporter gene (5HTT) is modulated by complex interaction of multiple genomic and cellular factors. Variability of a polymorphic repetitive element (5HTTLPR) is associated with anxiety, depression, and aggression-related traits and may influence the risk to develop affective spectrum disorders. 5HTTLPR variants display a unique DNA secondary structure that has the potential to regulate the transcriptional activity of the associated 5HTT promoter. The structure of the 5HTTLPR is also likely to precipitate a 381-bp somatic deletion in the 5HTT's promoter region [del(17)(q11.2)] that is observed in 20-60% of genomic DNA isolated from mononuclear blood cells and postmortem brain. The localization of the deletion breakpoints adjacent to identical putative signal sequences (CAGCC) suggests a V(D)J recombinase-like rearrangement event. In comparison with healthy controls, del(17)(q11.2)/wildtype sequence ratios showed a decrease of the deleted variant in recurrent unipolar depression. Our results also suggest that mosaicism of del(17)(q11.2) is likely to be regulated by tissue-specific as well as 5HTTLPR-dependent mechanisms. The findings confirm that the pericentric region of human chromosome 17 is highly unstable and furnishs additional evidence for intricate complexity of 5HTT regulation under physiological condition and in disease.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Würzburg, Federal Republic of Germany. kplesch@mail.uni-wuerzburg.de
authors.forename: K P
authors.initials: KP
authors.lastname: Lesch
authors.forename: S
authors.initials: S
authors.lastname: Jatzke
authors.forename: J
authors.initials: J
authors.lastname: Meyer
authors.forename: G
authors.initials: G
authors.lastname: Stöber
authors.forename: O
authors.initials: O
authors.lastname: Okladnova
authors.forename: R
authors.initials: R
authors.lastname: Mössner
authors.forename: P
authors.initials: P
authors.lastname: Riederer
mesh_terms: D000328:Adult; D000368:Aged; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D003863:Depression / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D008875:Middle Aged; D008969:Molecular Sequence Data; D009030:Mosaicism; D009419:Nerve Tissue Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011995:Recombination, Genetic / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins