English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Functional Analysis of a Potassium-Chloride Co-Transporter 3 (SLC12A6) Promoter Polymorphism Leading to an Additional DNA Methylation Site

Moser, D., Ekawardhani, S., Kumsta, R., Palmason, H., Bock, C., Athanassiadou, Z., et al. (2009). Functional Analysis of a Potassium-Chloride Co-Transporter 3 (SLC12A6) Promoter Polymorphism Leading to an Additional DNA Methylation Site. Neuropsychopharmacology, 34(2), 458-467. doi:10.1038/npp.2008.77.

Item is

Files

show Files
hide Files
:
Functional Analysis of a Potassium-Chloride Co-Transporter 3 (SLC12A6) Promoter Polymorphism.pdf (Any fulltext), 222KB
 
File Permalink:
-
Name:
Functional Analysis of a Potassium-Chloride Co-Transporter 3 (SLC12A6) Promoter Polymorphism.pdf
Description:
-
OA-Status:
Visibility:
Private
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Moser, Dirk, Author
Ekawardhani, Savira, Author
Kumsta, Robert, Author
Palmason, Haukur, Author
Bock, Christoph1, Author           
Athanassiadou, Zoi, Author
Lesch, Klaus-Peter, Author
Meyer, Jobst, Author
Affiliations:
1Computational Biology and Applied Algorithmics, MPI for Informatics, Max Planck Society, ou_40046              

Content

show
hide
Free keywords: -
 Abstract: The human potassium-chloride co-transporter 3 (KCC3, SLC12A6) is involved in cell proliferation and in electro-neutral movement of ions across the cell membrane. The gene (SLC12A6) is located on chromosome 15q14, a region that has previously shown linkage with bipolar disorder, schizophrenia, rolandic epilepsy, idiopathic generalized epilepsy, autism and attention deficit/hyperactivity disorder. Furthermore, recessively inherited mutations of SLC12A6 cause Andermann syndrome, characterized by agenesis of the corpus callosum, which is associated with peripheral neuropathy and psychoses. Recently, we have demonstrated the association of two G/A promoter polymorphisms of SLC12A6 with bipolar disorder in a case–control study, and familial segregation of the rare variants as well as a trend toward association with schizophrenia. To investigate functional consequences of these polymorphisms, lymphocyte DNA was extracted, bisulfite modified, and subsequently sequenced. To investigate SLC12A6 promoter activity, various promoter constructs were generated and analyzed by luciferase reporter gene assays. We provide evidence that the G- allele showed a significant reduction of reporter gene expression. In human lymphocytes, the allele harboring the rare upstream G nucleotide was found to be methylated at the adjacent C position, possibly accountable for tissue-specific reduction in gene expression in vivo. Here we demonstrate functionality of an SNP associated with psychiatric disease and our results may represent a functional link between genetic variation and an epigenetic modification.

Details

show
hide
Language(s): eng - English
 Dates: 2009-03-172008-06-042009
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 520920
DOI: 10.1038/npp.2008.77
Other: Local-ID: C125673F004B2D7B-0BB2B1FF18801B6BC12575220079A4C8-Moser2009
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Neuropsychopharmacology
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 34 (2) Sequence Number: - Start / End Page: 458 - 467 Identifier: ISSN: 0893-133X