ChapterHumanGeneMappingandDiseaseGeneIdentification精品.ppt

Chapter 10 Human Gene Mapping and Disease Gene Identification 第10章 人类基因的定位和疾病基因的鉴定 Two fundamental approaches to disease gene identification (2种鉴定疾病基因的基本方法) The first approach, linkage analysis, is family-based. Linkage analysis takes explicit advantage of family pedigrees to follow the inheritance of a disease over a few generations by looking for consistent, repeated inheritance of a particular region of the genome whenever the disease is passed on in a family. 一种是基于家系的连锁分析。连锁分析能直接利用系谱中几代之间特异基因组区域的一致的重复遗传方式来研究疾病的遗传。 The socond approach, association analysis, is population-based. Association analysis dose not depend explicitly on pedigrees but instead looks for increased or decreased frequency of a particular allele or set of alleles in a sample of affected individuals taken from the population, compared with a control set of unaffected people. Association analysis takes advantage of the entire history of a population to look for alleles that are found more or less frequently in patients with a disease compared with a control unaffected population. 另一种方法是基于群体的关联分析。关联分析不直接涉及系谱，但是却以群体为研究对象，比较群体中的患者和正常个体的一个或一组特异等位基因的频率。因此，关联分析是从一个群体的整个历史出发，通过与正常对照组对比，寻找患者更常见或更少见的疾病关联等位基因。 THE GENETIC LANDSCAPE OF THE HUMAN GENOME（人类基因组的遗传学全貌） How does gene mapping contribute to medical genetics? （基因定位对医学遗传学的贡献？） To develop indirect linkage methods for use in prenatal diagnosis, presymptomatic diagnosis, and carrier testing. 间接地进行连锁分析，从而实现产前诊断、症状前诊断和携带者筛查。 Positional cloning 定位克隆 To characterize the disorder as to the extent of locus heterogeneity, the spectrum of allelic heterogeneity, the frequency of various disease-causing or predisposing variants in various populations, the penetrance and positive predictive value of mutations, the fraction of the total genetic contribution to a disease attributable to the variant at any one locus, and the natural history of the disease in asymptomatic at-risk individuals. 疾病基因的定位克隆可以确定：疾病的基因座异质性，等位异质性范围，不同人群中各疾病易感基因变异体的频率，外显率和突变的阳性预测值，基因座变