Association mapping of disease loci, by use of a pooled DNA genomic screen
Association mapping of disease loci, by use of a pooled DNA genomic screen
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DOI：
10.1086/515512
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发表时间：
1997-09-01
影响因子：
9.8
通讯作者：
Thomson, G
中科院分区：
文献类型：
--
作者：
Barcellos, LF;Klitz, W;Thomson, G
通过关联来绘制疾病基因座的基因组筛选需要自动化，DNA样本的汇集，以及3,000-6,000个高度多态、均匀分布的微卫星标记。病例对照样本可以在初始筛查中使用，随后是基于家庭的数据，以确认标记关联。关联图谱与复杂疾病的遗传研究有关，在复杂疾病的遗传研究中，连锁分析可能不那么有效，也与难以获得多代数据的情况有关，包括罕见或晚发疾病和传染病。该方法还可以有效地用于跟踪和确认连锁研究中确定的区域或调查候选疾病基因座。研究设计可以通过在筛选前对样本进行适当细分来纳入疾病异质性和交互作用效应。在这里，我们报告使用混合DNA扩增--准确确定病例对照和核心家系数据的标记物-疾病相关性--包括口吃伪影和优先扩增校正方法的应用，这些问题与统计能力和实验设计的讨论相结合，定义了检测疾病位点的必要要求，同时几乎消除了假阳性，表明了使用联合DNA筛查进行关联映射的可行性和效率。
Genomic screening to map disease loci by association requires automation, pooling of DNA samples, and 3,000-6,000 highly polymorphic, evenly spaced microsatellite markers. Case-control samples can be used in an initial screen, followed by family-based data to confirm marker associations. Association mapping is relevant to genetic studies of complex diseases in which linkage analysis may be less effective and to cases in which multigenerational data are difficult to obtain, including rare or late-onset conditions and infectious diseases. The method can also be used effectively to follow up and confirm regions identified in linkage studies or to investigate candidate disease loci. Study designs can incorporate disease heterogeneity and interaction effects by appropriate subdivision of samples before screening. Here we report use of pooled DNA amplifications-the accurate determination of marker-disease associations for both case-control and nuclear family-based data-including application of correction methods for stutter artifact and preferential amplification, These issues, combined with a discussion of both statistical power and experimental design to define the necessary requirements for detecting of disease loci while virtually eliminating false positives, suggest the feasibility and efficiency of association mapping using pooled DNA screening.