Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder

Citation
J. Veenstra-vanderweele et al., Genomic organization of the SLC1A1/EAAC1 gene and mutation screening in early-onset obsessive-compulsive disorder, MOL PSYCHI, 6(2), 2001, pp. 160-167
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
MOLECULAR PSYCHIATRY
ISSN journal
1359-4184 → ACNP
Volume
6
Issue
2
Year of publication
2001
Pages
160 - 167
Database
ISI
SICI code
1359-4184(200103)6:2<160:GOOTSG>2.0.ZU;2-V
Abstract
The first genome scan conducted in early-onset obsessive-compulsive disorde r used a nonparametric analysis to identify a peak in a region of chromosom e 9 containing the gene SLC1A1, which codes for the neuronal and epithelial glutamate transporter EAAC1. Interaction between the glutamatergic and ser otonergic systems within the striatum suggests EAAC1 as a functional candid ate in OCD as well. We determined the genomic organization of SLC1A1 primar ily by using primers designed from cDNA sequence to amplify from adaptor-li gated genomic DNA restriction fragments, In order to confirm SLC1A1 as a po sitional candidate in early-onset OCD, common single nucleotide polymorphis ms (SNPs) were identified that enabled mapping of SLC1A1 within the region of the lod score peak. Based on the linkage evidence, the coding region was sequenced in the probands of the seven families included in the genome sca n. No evidence was found far a functional mutation, but several SNPs were i dentified. Capillary electrophoresis SSCP typing of a haplotype consisting of two common SNPs within EAAC1 revealed no significant linkage disequilibr ium.