De La Vega Francisco M
Applied Biosystems, Foster City, CA, USA.
Methods Mol Biol. 2007;376:177-93. doi: 10.1007/978-1-59745-389-9_13.
The design of genetic association studies using single-nucleotide polymorphisms (SNPs) requires the selection of subsets of the variants providing high statistical power at a reasonable cost. SNPs must be selected to maximize the probability that a causative mutation is in linkage disequilibrium (LD) with at least one marker genotyped in the study. The HapMap Project performed a genome-wide survey of genetic variation with over 3 million SNPs typed in four populations, providing a rich resource to inform the design of association studies. A number of strategies have been proposed for the selection of SNPs based on observed LD, including construction of metric LD maps and the selection of haplotype-tagging SNPs. Power calculations are important at the study design stage to ensure successful results. Integrating these methods and annotations can be challenging: the algorithms required to implement these methods are complex to deploy, and all the necessary data and annotations are deposited in disparate databases. Here, we review the typical workflows for the selection of markers for association studies utilizing the SNPbrowser software, a freely available, stand-alone application that incorporates the HapMap database together with gene and SNP annotations. Selected SNPs are screened for their conversion potential to genotyping platforms, expediting the set up of genetic studies with an increased probability of success.
利用单核苷酸多态性（SNP）进行基因关联研究的设计需要选择变异子集，以便在合理成本下提供高统计效能。必须选择SNP，以使致病突变与研究中至少一个进行基因分型的标记处于连锁不平衡（LD）状态的概率最大化。国际人类基因组单体型图计划（HapMap计划）对四个群体中超过300万个SNP进行了全基因组遗传变异调查，为关联研究的设计提供了丰富资源。已经提出了许多基于观察到的LD来选择SNP的策略，包括构建度量LD图谱和选择单倍型标签SNP。在研究设计阶段进行效能计算对于确保获得成功结果很重要。整合这些方法和注释可能具有挑战性：实施这些方法所需的算法部署起来很复杂，而且所有必要的数据和注释都存放在不同的数据库中。在这里，我们回顾了利用SNPbrowser软件选择关联研究标记的典型工作流程，该软件是一个免费的独立应用程序，它整合了HapMap数据库以及基因和SNP注释。对选定的SNP进行其向基因分型平台转化潜力的筛选，加快遗传研究的建立，提高成功概率。
