Veenstra-VanderWeele J, Kim S J, Gonen D, Hanna G L, Leventhal B L, Cook E H
Laboratory of Developmental Neuroscience, Child and Adolescent Psychiatry, Department of Psychiatry, University of Chicago, MC3077, 5841 S Maryland Avenue, Chicago, IL 60637, USA.
Mol Psychiatry. 2001 Mar;6(2):160-7. doi: 10.1038/sj.mp.4000806.
The first genome scan conducted in early-onset obsessive-compulsive disorder used a non-parametric analysis to identify a peak in a region of chromosome 9 containing the gene SLC1A1, which codes for the neuronal and epithelial glutamate transporter EAAC1. Interaction between the glutamatergic and serotonergic systems within the striatum suggests EAAC1 as a functional candidate in OCD as well. We determined the genomic organization of SLC1A1 primarily by using primers designed from cDNA sequence to amplify from adaptor-ligated genomic DNA restriction fragments. In order to confirm SLC1A1 as a positional candidate in early-onset OCD, common single nucleotide polymorphisms (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 scan. No evidence was found for a functional mutation, but several SNPs were identified. Capillary electrophoresis SSCP typing of a haplotype consisting of two common SNPs within EAAC1 revealed no significant linkage disequilibrium.
在早发性强迫症中进行的首次全基因组扫描使用非参数分析，以确定9号染色体上包含基因SLC1A1的区域出现的一个峰值，该基因编码神经元和上皮谷氨酸转运体EAAC1。纹状体内谷氨酸能系统和5-羟色胺能系统之间的相互作用也表明EAAC1是强迫症的一个功能候选基因。我们主要通过使用根据cDNA序列设计的引物，从衔接子连接的基因组DNA限制性片段中扩增，来确定SLC1A1的基因组结构。为了确认SLC1A1是早发性强迫症的一个定位候选基因，我们鉴定了常见的单核苷酸多态性（SNP），从而能够在对数优势比分峰值区域内对SLC1A1进行定位。基于连锁证据，对基因组扫描中纳入的7个家系的先证者的编码区进行了测序。未发现功能突变的证据，但鉴定出了几个SNP。对由EAAC1内两个常见SNP组成的单倍型进行毛细管电泳SSCP分型，未发现显著的连锁不平衡。
