An Innovative, High-Throughput Method of SNP Haplotyping

描述(由申请人提供)：目标是提炼一种新的、高通量的单核苷酸多态(SNPs)单倍型分析方法，并开发具有重大科学/临床和商业意义的特定单倍型的分析方法。目前，还没有简单、可靠、准确的高通量SNP单倍型方法。应用包括：1)筛选与特定疾病易感性相关的大量样本的单倍型；2)与疾病易感性、药物遗传学和免疫学相关的单倍型诊断测试；3)利用单倍型缩小基于单个SNPs的连锁研究确定的候选基因组区域的饱和基因分型；以及4)位于候选基因组区域或通过其他方法确定的候选基因的连锁不平衡和关联研究。 I期活动将基于平板的2-SNP单倍型分析转变为基于多SNP珠的单倍型分析，显著提高了产量和重复性，同时减少了成本、劳动力和时间，并证明了在单倍化E-选择素基因方面的实用价值。 第二阶段的目标是： 1)减少化验开发工作量和化验成本； 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体鉴定，包括单项和多重分析。 3)开发在科学文献和/或HapMap数据库中确定的具有潜在临床/科学/商业价值的单倍型的分析方法，以寻找推定有价值的基因。

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.