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[精神疾病行为遗传学的研究方法]

[Research approaches in the behavioral genetics of psychiatric disorders].

作者信息

Shamir Alon, Shaltiel Galit

机构信息

Zlotowski Center for Neuroscience, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

出版信息

Harefuah. 2002 May;141(5):455-61, 497.

Abstract

Multi-factorial inheritance combines genetic and environmental effects. Each factor contributes a relatively small part to the overall phenotype. Multi-factorial multi-genetic illnesses are usually divided into two categories: 1. Continuous variation of the normal distribution--phenotypes that can be measured within the normal scale (i.e. blood pressure). A normal distribution is obtained and the mean is in the middle. 2. Multi-factorial threshold trait--a threshold separates between the existence or absence of the phenotype. The curve of distribution obtained only predicts sensitivity for the illness rather than it's existence, since the illness appears only beyond a specific threshold, which represents a specific combination of defected genes. Mental illnesses (psychoses, affective disorders and neuroses) are multi-factorial illnesses, affected at a level of approximately 50% by inheritance. These diseases are not inherited in a simple Mendelian way, and, most probably, many genes are involved. Today, there is still no biochemical or molecular marker for any of the mental illnesses, and diagnosis of patients is obtained according to behavioral accepted scales. The aim of behavioral genetics is to understand the interaction between genes and behavioral variability among individuals. Most behaviors are complex, and when a genetic influence is observed, we can not point at a single responsible gene. Behavioral genetics targets to identify multiple genes and to understand the contribution of each of them to a specific behavioral trait. Methods to study multi-gene diseases include linkage analysis, family studies, twin and adoption studies, search for candidate genes affected by drug therapy of the patients, analysis of candidate genes using knockout mice and SNP's, methods that identify the effect of specific genes on behavior by QTL, and gene expression using DNA differential display and DNA microarray chips. The present review summarizes and exemplifies these issues.

摘要

多因素遗传结合了遗传和环境效应。每个因素对整体表型的贡献相对较小。多因素多基因疾病通常分为两类:1. 正态分布的连续变异——可在正常范围内测量的表型(即血压)。获得正态分布,且均值位于中间。2. 多因素阈值性状——一个阈值将表型的存在与否区分开来。所获得的分布曲线仅预测对该疾病的易感性而非其存在情况,因为该疾病仅在特定阈值之外出现,该阈值代表缺陷基因的特定组合。精神疾病(精神病、情感障碍和神经症)是多因素疾病,约50%受遗传影响。这些疾病并非以简单的孟德尔方式遗传,而且很可能涉及许多基因。如今,仍没有任何精神疾病的生化或分子标志物,患者的诊断是根据行为公认量表进行的。行为遗传学的目的是了解基因与个体间行为变异性之间的相互作用。大多数行为都很复杂,当观察到遗传影响时,我们无法指出单个负责的基因。行为遗传学旨在识别多个基因,并了解它们各自对特定行为特征的贡献。研究多基因疾病的方法包括连锁分析、家族研究、双胞胎和收养研究、寻找受患者药物治疗影响的候选基因、使用基因敲除小鼠和单核苷酸多态性分析候选基因、通过数量性状位点确定特定基因对行为的影响的方法,以及使用DNA差异显示和DNA微阵列芯片进行基因表达分析。本综述总结并举例说明了这些问题。

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