Molecular Haplotyping of Long Genomic Distances of DNA

DNA 长基因组距离的分子单倍型分析

• 批准号: 6832454
• 负责人: BAOCHUAN GUO
• 金额: $ 10万
• 依托单位: GLC BIOTECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-29 至 2005-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6832454
• 关键词: Crohn' s disease; apolipoprotein E; clinical research; family genetics; genetic polymorphism; genetic susceptibility; genotype; high throughput technology; human genetic material tag; human tissue; method development; molecular pathology; nucleic acid hybridization; nucleic acid probes; nucleic acid purification; nucleic acid quantitation /detection; nucleic acid sequence; nucleic acid structure; patient oriented research

This SBIR project is proposed to commercialize a novel method referred as PDESA for revealing patient's individual haplotypes. Our preliminary data shown that PDESA could reveal haplotypes of sequences of 134kb in length, which is about three times longer than the longest sequence haplotyped using other molecular methods. PDESA is simple, easy to implement, and importantly, it works! Thus, this project is warranted. Phase I of this SBIR project is to further demonstrate the feasibility of PDESA and the specific aims of Phase I are: Aim 1: applying PEDSA to hapiotyping a sequence block near the IBD5 locus to establish the fact that PDESA is indeed, a robust, general molecular method for haplotyping; Aim 2: evaluating the accuracy of PDESA by haplotyping a family with a total of 16 individuals in both the ApoE4 and IBD5 loci; and Aim 3: demonstrating the feasibility of using PDESA to haplotype ultra long distances of genomic DNA (longer than 150kb). The goals in Phase II will be (1) to develop the assays that meet the requirements of clinical applications; (2) to develop rapid, easy kits for haplotyping a number of genes of functional and clinical significance, including both individual and multiplexed assays; (3) to develop assays for haplotyping of potential clinical and commercial value, identified in the scientific literature and/or HAPmap database for genes presumed to have values. By the end of this project, we shall have many well-developed assays that are ready to implement for haplotyping both short and long distances of DNA in an accurate, robust, low-cost, high-throughput manner. Thus, success of this project will not only be of commercial significance to GLC Biotechnology Inc., but also will have profound impacts on many fields, particularly on pharmacogenetics, and personalized medicine.

这个SBIR项目是为了将一种名为PDESA的新方法商业化，该方法用于揭示患者的个体单倍型。我们的初步数据显示，PDESA可以揭示134kb的序列单倍型，大约是其他分子方法单倍型最长序列的三倍。PDESA很简单，很容易实现，而且重要的是，它有效！因此，这个项目是值得的。这项SBIR项目的第一阶段是为了进一步证明PDESA的可行性，第一阶段的具体目的是：目的1：应用PEDSA对IBD5基因座附近的序列块进行单倍型分析，以确定PDESA确实是一种可靠的、通用的单倍化分子方法；目标2：通过对一个在ApoE4和IBD5基因座上都有16个个体的家庭进行单倍化来评估PDESA的准确性；以及目标3：证明使用PDESA对超长距离基因组DNA(大于150kb)进行单倍化的可行性。第二阶段的目标是(1)开发符合以下要求的分析方法 为满足临床应用的需要，(2)开发快速、简便的试剂盒，用于对一些具有功能和临床意义的基因进行单倍型分析，包括单独和多重分析；(3)开发在科学文献和/或HapMap数据库中确定的具有潜在临床和商业价值的单倍型分析方法，以寻找被认为有价值的基因。到这个项目结束时，我们将有许多发展良好的分析方法，准备好以准确、可靠、低成本、高通量的方式实施短距离和长距离DNA单倍体鉴定。因此，这个项目的成功将不仅仅是商业上的 对GLC生物技术公司具有重要意义，但也将对许多领域产生深远影响，特别是在药物遗传学和个性化医学方面。