DEVELOPMENT OF SNP ANALYSIS FOR GENETIC VARIATION

遗传变异 SNP 分析的发展

• 批准号: 6073973
• 负责人: CHRISTOPHER H BECKER
• 金额: $ 9.93万
• 依托单位: GENETRACE SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2000-03-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6073973
• 关键词: DNA primers; biomedical automation; computer program /software; computer system design /evaluation; genetic markers; genetic polymorphism; genetic techniques; human genetic material tag; mass spectrometry; polymerase chain reaction; technology /technique development

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.

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（SNP）的常见发生。这些遗传变异也可能涉及许多复杂的疾病。 提出了开发用于SNP分析的全自动质谱分析方法。 在延伸反应中将使用新的可切割引物;这种方法有利于短的所得寡核苷酸的容易的多路复用和纯化。 每个（多重）样品的测量时间小于5秒，添加的碱的质量测量的标准偏差小于2道尔顿。 研发工作将集中在提高多重引物探针设计、多重SNP数据分析、验证研究和自动化开发的简便性和稳健性。单核苷酸多态性（SNP）在人类基因组中的高频率使其成为用于身份测试、基因组作图、风险评估和医学诊断的遗传标记的有价值的来源。 SNP的测定在制药工业中具有潜在的商业应用，用于预防、诊断和治疗其中个体的易感性和治疗结果与特定遗传多态性相关的疾病。 由于可能需要筛选数百至数千个个体的许多遗传基因座，以评估特定遗传变异的意义，因此检测的高通量能力将尤为重要。