An Innovative, High-Throughput Method of SNP Haplotyping

描述（由申请人提供）：目的是完善一种用于单核苷酸多态性（SNP）单倍型分析的新型高通量方法，并开发具有重要科学/临床和商业相关性的特定单倍型的检测方法。目前，没有简单、可靠、准确的方法用于高通量SNP单体型分型。应用程序是; 1）筛选与特定疾病易感性相关的单倍型的大量样品; 2）与疾病易感性、药物遗传学和免疫学谱相关的单倍型的诊断测试; 3）使用单倍型的饱和基因分型，以缩小基于个体SNP的连锁研究所定义的候选基因组区域; 4）位于候选基因组区域的基因或通过其他方法鉴定的候选基因的连锁不平衡和关联研究。 I期活动将基于板的2-SNP单体型分析转化为基于多SNP珠的分析，产生显著的通量和再现性改善，同时降低成本、劳动力和时间，并证明了在E-选择素基因单体型分析中的实用性。 第二阶段的目标是： 1)减少分析开发工作和分析成本; 2)开发快速、简便的试剂盒，用于对几种具有功能和临床意义的细胞因子进行单倍型分型，包括单独和多重检测 3)开发具有潜在临床/科学/商业价值的单倍型的检测方法，这些单倍型在科学文献和/或HAPMap数据库中被确定为具有价值的基因。

DESCRIPTION (provided by applicant): Objectives are refining a novel, high-throughput method for haplotype analysis of single nucleotide polymorphisms (SNPs) and developing assays for specific haplotypes of significant scientific/clinical and commercial relevance. Presently, no simple, reliable, accurate methods exist for high-throughput SNP haplotyping. Applications are; 1) screening large numbers of samples for haplotypes associated with susceptibility to a particular disease; 2) diagnostic tests for haplotypes associated with disease susceptibility, pharmacogenetic and immunologic profiling; 3) saturation genotyping using haplotypes to narrow candidate genomic regions defined by linkage studies based on individual SNPs; and 4) linkage disequilibrium and association studies of genes located in candidate genomic regions or candidate genes identified by other methods. Phase I activities converted a plate-based 2-SNP haplotyping assay to a multi-SNP bead-based assay yielding dramatic throughput and reproducibility improvements while decreasing cost, labor and time, and demonstrated utility in haplotyping the E-selectin gene. Phase II aims are: 1) To reduce assay development effort and assay cost; 2) To develop rapid, easy kits for haplotyping several cytokines of functional and clinical significance, including both individual and multiplexed assays 3) To develop assays for haplotypes of potential clinical/scientific/commercial value, identified in the scientific literature and/or HAPMap database for genes presumed to have value.