DEVELOPMENT OF SNP ANALYSIS FOR GENETIC VARIATION

个体之间的遗传变异在很大程度上是由于单核苷酸多态性（SNPs）的普遍存在。这些遗传变异也可能与许多复杂的疾病有关。建议开发一种全自动的质谱分析方法用于SNP分析。一种新型可切割引物将用于延伸反应；这种方法有利于合成的短寡核苷酸的容易多路复用和纯化。每个（多路复用）样品的测量时间小于5秒，添加基的质量测量的标准偏差小于2道尔顿。研发工作将集中在增加多重引物探针设计、多重SNP数据分析、验证研究和自动化开发的易用性和稳健性上。人类基因组中单核苷酸多态性（snp）的高频率使其成为身份检测、基因组定位、风险评估和医学诊断的有价值的遗传标记来源。单核苷酸多态性测定在制药工业中具有潜在的商业应用，用于预防、诊断和治疗个人的易感性和治疗结果与特定遗传多态性有关的疾病。为了评估特定遗传变异的重要性，可能需要筛选数百到数千个个体的许多遗传位点，因此该检测的高通量能力将尤为重要。

Genetic variation between individuals is due in large part to the common occurrence of single nucleotide polymorphisms (SNPs). These genetic variations are also likely to be involved in numerous complex diseases. It is proposed to develop a fully automated mass spectrometric assay for SNP analysis. A novel cleavable primer will be used in an extension reaction; this approach is advantageous for facile multiplexing and purification of the short resultant oligonucleotides. Measurement times are less than five seconds per (multiplexed) sample, with standard deviations in mass measurement of the added base of less than two Daltons. R and D work will center on increasing the ease and robustness of multiplex primer-probe design, multiplex SNP data analysis, validation studies, and automation development. PROPOSED COMMERCIAL APPLICATION The high frequency of single nucleotide polymorphisms (SNPs) in the human genome makes them a valuable source of genetic markers for identity testing, genome mapping, risk assessment, and medical diagnostics. Assays for SNPs have potential commercial applications in the pharmaceutical industry for the prevention, diagnosis and treatment of diseases where the susceptibility of individuals and the outcome of treatment is related to particular genetic polymorphisms. Because it is likely that many genetic loci from hundred to thousands of individuals will need to be screened in order to assess the significance of specific genetic variants, the high-throughput capabilities of the assay will be especially important.