Linkage disequilibrium mapping of schizophrenia susceptibility to the CAPON region of chromosome 1q22
Linkage disequilibrium mapping of schizophrenia susceptibility to the CAPON region of chromosome 1q22
复制标题
DOI：
10.1086/420774
复制
发表时间：
2004-05-01
影响因子：
9.8
通讯作者：
Bassett, AS
中科院分区：
文献类型：
--
作者：
Brzustowicz, LM;Simone, J;Bassett, AS
在此之前，我们已经报道了染色体1q22标记与精神分裂症的连锁，这一发现得到了几项独立研究的支持。我们现在已经研究了该地区的连锁不平衡（LD）的证据，在加拿大的24个家庭精神分裂症家系样本的最强联系。对D1S1653和D1S1677之间5.4Mb区域的14个微卫星和15个单核苷酸多态性（SNPs）的分析产生了精神分裂症与2个微卫星和6个SNPs之间LD的显著证据（名义P <0.05）。所有表现出显着LD精神分裂症的标记属于基因组范围内的羧基末端PDZ配体的神经元型一氧化氮合酶（CAPON），使其成为一个主要的位置候选人的精神分裂症易感基因座1q22，虽然该基因的初始突变分析尚未确定任何精神分裂症相关的变化外显子。与最近发现的几个精神分裂症候选基因一致，CAPON参与NMDA受体系统的信号转导，突出了该途径在精神分裂症病因学中的潜在重要性。
Previously, we have reported linkage of markers from chromosome 1q22 to schizophrenia, a finding supported by several independent studies. We have now examined the region of strongest linkage for evidence of linkage disequilibrium (LD) in a sample of 24 Canadian familial-schizophrenia pedigrees. Analysis of 14 microsatellites and 15 single-nucleotide polymorphisms (SNPs) from the 5.4-Mb region between D1S1653 and D1S1677 produced significant evidence (nominal P < .05) of LD between schizophrenia and 2 microsatellites and 6 SNPs. All of the markers exhibiting significant LD to schizophrenia fall within the genomic extent of the gene for carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON), making it a prime positional candidate for the schizophrenia-susceptibility locus on 1q22, although initial mutation analysis of this gene has not identified any schizophrenia-associated changes within exons. Consistent with several recently identified candidate genes for schizophrenia, CAPON is involved in signal transduction in the NMDA receptor system, highlighting the potential importance of this pathway in the etiology of schizophrenia.