Schork N J, Fallin D, Lanchbury J S
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
Clin Genet. 2000 Oct;58(4):250-64. doi: 10.1034/j.1399-0004.2000.580402.x.
In this review, we consider the motivation behind contemporary single nucleotide polymorphism (SNP) initiatives. Many of these initiatives are projected to involve large, population-based surveys. We therefore emphasize the utility of SNPs for genetic epidemiology studies. We start by offering an overview of genetic polymorphism and discuss the historical use of polymorphism in the identification of disease-predisposing genes via meiotic mapping. We next consider some of the unique aspects of SNPs, and their relative advantages and disadvantages in human population-based analyses. In this context, we describe and critique the following six different areas of application for SNP technologies: Gene discovery and mapping. Association-based candidate polymorphism testing. Diagnostics and risk profiling. Prediction of response to environmental stimuli, xenobiotics and diet. Homogeneity testing and epidemiological study design. Physiologic genomics. We focus on key issues within each of these areas in an effort to point out potential problems that might plague the use of SNPs (or other forms of polymorphism) within them. However, we make no claim that our list of considerations are exhaustive. Rather, we believe that they may provide a starting point for further dialog about the ultimate utility of SNP technologies. In addition, although our emphasis is placed on applications of SNPs to the understanding of human phenotypes, we acknowledge that SNP maps and technologies applied to other species (e.g. the mouse genome, pathogen genomes, plant genomes, etc.) are also of tremendous interest.
在本综述中，我们探讨当代单核苷酸多态性（SNP）研究项目背后的动机。其中许多项目预计将涉及大规模的人群调查。因此，我们强调SNP在遗传流行病学研究中的作用。我们首先概述遗传多态性，并讨论多态性在通过减数分裂图谱鉴定疾病易感基因方面的历史应用。接下来，我们考虑SNP的一些独特方面，以及它们在基于人群的人类分析中的相对优缺点。在此背景下，我们描述并评论SNP技术的以下六个不同应用领域：基因发现与定位；基于关联的候选多态性检测；诊断与风险评估；对环境刺激、异生素和饮食反应的预测；同质性检测与流行病学研究设计；生理基因组学。我们关注这些领域中的关键问题，旨在指出可能困扰SNP（或其他形式多态性）在这些领域应用的潜在问题。然而，我们并不认为我们所考虑的内容详尽无遗。相反，我们相信它们可能为进一步讨论SNP技术的最终效用提供一个起点。此外，尽管我们的重点是SNP在理解人类表型方面的应用，但我们承认应用于其他物种（如小鼠基因组、病原体基因组、植物基因组等）的SNP图谱和技术也极具吸引力。
