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精神分裂症与位于α7-烟碱型乙酰胆碱受体亚基基因(CHRNA7)15q13-14染色体位点的连锁不平衡。

Linkage disequilibrium for schizophrenia at the chromosome 15q13-14 locus of the alpha7-nicotinic acetylcholine receptor subunit gene (CHRNA7).

作者信息

Freedman R, Leonard S, Gault J M, Hopkins J, Cloninger C R, Kaufmann C A, Tsuang M T, Farone S V, Malaspina D, Svrakic D M, Sanders A, Gejman P

机构信息

Department of Psychiatry, University of Colorado Health Sciences Center, Denver 80262, USA.

出版信息

Am J Med Genet. 2001 Jan 8;105(1):20-2.

Abstract

The transmission/disequilibrium test was used for fine mapping of the linkage of schizophrenia to the chromosome 15q13-14 region, the site of a candidate gene, the alpha7 nicotinic acetylcholine receptor subunit gene (CHRNA7), in parent-child triads from the NIMH Schizophrenia Genetics Initiative families. This candidate gene was identified from neurobiological studies of deficits in schizophrenics of the inhibitory gating of the P50 auditory evoked potential. The neurobiological deficit was also used as a phenotype for subsequent linkage analysis. In the present study, significant genotype-wise disequilibrium (P < 0.007) was found at D15S165, a polymorphic simple sequence marker physically located within 1 megabase of both CHRNA7 and a partially duplicated, expressed sequence that includes exons 5-10 of CHRNA7. Replication of this result was found in an additional set of families. The results support this region as a chromosomal location involved in the genetic transmission of schizophrenia.

摘要

传递/不平衡检验用于对精神分裂症与15号染色体q13 - 14区域(一个候选基因——α7烟碱型乙酰胆碱受体亚基基因(CHRNA7)所在位点)之间的连锁进行精细定位,该检验在来自美国国立精神卫生研究所精神分裂症遗传学计划家庭的亲子三联体中进行。这个候选基因是从对精神分裂症患者P50听觉诱发电位抑制性门控缺陷的神经生物学研究中鉴定出来的。这种神经生物学缺陷也被用作后续连锁分析的一种表型。在本研究中,在D15S165处发现了显著的基因型不平衡(P < 0.007),D15S165是一个多态性简单序列标记,其物理位置在CHRNA7以及一个部分重复的、包含CHRNA7外显子5 - 10的表达序列的1兆碱基范围内。在另一组家庭中发现了这一结果的重复。这些结果支持该区域是参与精神分裂症遗传传递的一个染色体位置。

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