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Functional polymorphisms in dopamine and serotonin pathway genes

D'Souza, Ursula M. ; Craig, Ian W.

Human mutation, 2006-01, Vol.27 (1), p.1-13 [Periódico revisado por pares]

Hoboken: Wiley Subscription Services, Inc., A Wiley Company

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  • Título:
    Functional polymorphisms in dopamine and serotonin pathway genes
  • Autor: D'Souza, Ursula M. ; Craig, Ian W.
  • Assuntos: Animals ; Behavior disorders ; Dopamine ; Dopamine - metabolism ; functional polymorphism ; Gene expression ; Humans ; Medical imaging ; monoamine neurotransmitter pathway ; Mutation ; Neuroimaging ; Polymorphism, Genetic - genetics ; Psychiatry ; Receptors, Dopamine - metabolism ; Receptors, Serotonin - metabolism ; regulatory ; Schizophrenia ; Serotonin ; Serotonin - metabolism
  • É parte de: Human mutation, 2006-01, Vol.27 (1), p.1-13
  • Notas: ark:/67375/WNG-JCRMSJJT-7
    ArticleID:HUMU20278
    Communicated by Christine Van Broeckhoven
    istex:DC9B9866CE1153EFCA7B8A18B6280E592042A7F6
    ObjectType-Article-2
    SourceType-Scholarly Journals-1
    ObjectType-Feature-3
    content type line 23
    ObjectType-Review-1
  • Descrição: There is mounting evidence on the functional significance of single nucleotide and simple repeat sequence polymorphisms in both the coding and regulatory regions of genes in the monoamine neurotransmitter pathways. Many of these gene variants have been associated with human behavioral disorders and traits, and thus have important clinical relevance. This review summarizes the literature on the published functional studies from a molecular, cellular, and neurobiological perspective, and notes their possible behavioral consequences. Functional studies have adopted a variety of strategies. Pharmacological studies have focused on the effects of gene variation at the protein level in terms of binding to ligands or drugs. Other key investigations have determined effects on gene expression at the level of transcription in mammalian cell cultures, lymphoblasts, and/or human postmortem brain tissue. This has enabled the comparison of in vitro and in vivo data, and furthermore provides an improved perceptive of their respective advantages. Additionally, molecular biological approaches have identified transcription factors (DNA‐binding proteins) that interact with the motifs within the polymorphisms themselves. Various neuroimaging studies have further determined the relationship of genotype with protein availability in the brain, and thus have contributed to our understanding of the in vivo functional significance of gene variants. Finally, there is growing evidence from both human and animal studies on the interaction of functional polymorphisms with the environment in determining a behavioral outcome. Taken together, these findings have contributed to a greater understanding of the plausible molecular mechanisms that underpin the functional significance of polymorphisms in monoamine neurotransmitter pathway genes, and how they may influence behavioral phenotypes. Hum Mutat 27(1), 1–13, 2006. © 2005 Wiley‐Liss, Inc.
  • Editor: Hoboken: Wiley Subscription Services, Inc., A Wiley Company
  • Idioma: Inglês
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