c-Kit基因与抑郁症关联分析_生物技术.rar

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摘要:抑郁症是一种常见的精神疾病,主要表现为情绪低落、兴趣减退、悲观、思维迟缓、缺乏主动性、自责自罪、饮食睡眠差、身体不适等,严重者可出现自杀念头和行为。抑郁症是精神科自杀率最高的疾病,在西方被称为“蓝色隐忧”,据有关调查显示,在我国抑郁症发病率约为3%-5%,情况也不容乐观。

  目前对于抑郁症具体是由什么引起的还没有完全了解。大多认为抑郁症是各种遗传、心理和环境因素复杂相互作用的结果。关于抑郁症的产生机理,神经递质学说得到了广泛的认同,普遍认为,是神经系统中的去甲肾上腺素、5-羟色胺、多巴胺、乙酰胆碱等神经递质的水平影响了情绪状况。

  c-Kit是一种原癌基因,编码受体酪氨酸激酶家族的一种跨膜蛋白c-Kit,配体为SCF(Stem cell factor,Kitl)。SCF/c-Kit信号在发育以及疾病发生中扮演着重要作用,影响造血系统、生殖系统、消化系统及神经系统等,目前研究表明,c-Kit基因的突变会导致这些系统的发育失常,甚至会引起各种癌症。

  很早已经知道,c-Kit受体及其配体SCF在中枢神经系统(CNS)和外周神经系统(PNS)中都有表达,尤其在中枢神经系统中起重要作用。

  我们实验室发现c-Kit突变体小鼠在行为学实验中表现出抑郁症表型,猜测c-Kit基因与抑郁症的产生可能有一定关系。在实验中选择了c-Kit基因中的9个SNP位点及一个ENU突变鼠中的突变位点作为遗传标记,通过对抑郁症患者和正常对照人群的DNA样本各288个进行扩增测序进行基因分型,运用统计学分析手段检测c-Kit基因和抑郁症的关联程度。

关键词:抑郁症,c-Kit/SCF,关联分析,SNP(单核甘酸多态性)

 

Abstract:Depression is a common kind of mental diseases, characterized by being "down in the dumps”, decreased energy, retardation, lack of initiative, feels of guilt, insomnia, loss of appetite, Chronic aches and pains, and even thoughts or behavior of suicide. Among all mental diseases, the ratio of patients committing suicide of depression is the largest. Depression affects approximately 19 million Americans, or 9.5% of the population in any given one-year period. In China, the situation is no better, as depression affects about 3% to 5% of the population according to some reports.

  Up to now, the exact causes of depression have not been fully known. It is generally believed that depression is most often caused by the combination of biological and genetic factors, environmental influence, psychological factor, medical illness, and so on. Referring to the biological mechanism of depression, neurotransmitter hypothesis has been widely accepted. Levels of some neurotransmitters such as noradrenalin, 5-HT, dopamine, acetylcholine are thought to be able to affect mood condition. 

  c-Kit is a proto-oncogene and codes a transmembrane protein c-Kit, a member of receptor tyrosine kinase family. SCF is its ligand. SCF/c-Kit signaling plays an important role in development and human diseases, affecting hematopoietic system, digestive system, reproductive system, nervous system, etc. It has been shown that mutations of c-Kit result in abnormal development of these systems, and even cancers.

  Previous researches have demonstrated that c-Kit and its ligand SCF express in both central nervous system (CNS) and peripheral nervous system (PNS), and this c-Kit/SCF signaling is of great importance in CNS.

  We found c-Kit mutant mice showed depression-like behaviors in behavior tests and this fact suggests there might be some association between c-Kit gene and depression. In order to explore this kind of association, Here we select 9 SNPs and a mutant site of ENU induced mutant mice as genetic markers. Through amplification, sequencing and genotyping of 288 DNA samples of depression patients and 288 control DNA samples, we study the association of c-Kit gene and depression, using statistic analysis. 

Key words: depression, c-Kit/SCF, association study, SNP