HUMAN DIALLELIC INSERTION/DELETION OF POLYMORPHISMS

描述：(申请者摘要)发现人类DNA多态 在许多研究和临床测试领域中的应用，特别是在 致病基因的连锁图谱。短串联重复序列 多态目前是这些应用的选择标记， 但双等位基因多态最终可能会取代STRP，因为 对微型DNA阵列(DNA芯片)进行更高效的分析。的目标 本研究项目是第一个，开发1500个新的人类双等位基因 短插入/缺失类的多态，第二，调查 新的方法，并加强现有的分析方法 DNA基因感受器上的插入/缺失多态，第三， 逐步引入基于芯片的双等位基因分析 在马什菲尔德的基因分型工厂。双等位短 插入/缺失多态与碱基相比有许多优势 替代多态，尤其是改良杂交的多态 等位基因之间的区别。新的、假定的插入/删除 多态将通过比较公共可用的重叠来识别 基因组和编码DNA序列。假定的多态将得到确认 通过实验室打字。等位基因频率将按以下几组进行测量 有美洲、欧洲、非洲和亚洲血统的人。戴维斯博士。 橡树岭国家实验室的Beattie和Doktycz在 新型多孔DNA芯片材料，特别是毛细管通道玻璃。这个 与传统芯片相比，多孔芯片支持提高杂交反应动力学 扁平的薯条。芯片生产的协议将得到改进，用于 将DNA靶标与芯片杂交，并用于检测 杂交的DNA。许多新的多态性分析方法绕过 杂交靶标的聚合酶链式反应扩增要求为 探索过了。芯片阵列和读数的仪器设备将得到改进。 最后，用于识别短插入/缺失多态的DNA芯片将是 逐步引入马什菲尔德的基因分型工厂以补充 STRP分型在疾病基因连锁分析中的应用。

DESCRIPTION: (Applicant's abstract) Human DNA polymorphisms find application in many areas of research and clinical testing, particularly in the linkage mapping of genes responsible for disease. Short tandem repeat polymorphisms are currently the markers of choice for these applications, but diallelic polymorphisms will likely eventually replace STRPs because of more efficient analysis on miniaturized DNA arrays (DNA chips). Goals of this research project are first, to develop 1,500 new human diallelic polymorphisms of the short insertion/deletion class, second, to investigate new approaches and to enhance existing approaches for the analysis of the insertion/deletion polymorphisms on flow through DNA genosensors, and third, to gradually introduce the chip-based analysis of the diallelic polymorphisms into the genotyping factory at Marshfield. Diallelic short insertion/deletion polymorphisms have a number of advantages over base substitution polymorphisms, especially that of improved hybridization discrimination between alleles. New, putative insertion/deletion polymorphisms will be identified by comparing publicly available overlapping genomic and coding DNA sequences. Putative polymorphisms will be confirmed by laboratory typing. Allele frequencies will be measured in groups of individuals with American, European, African, and Asian ancestry. Drs. Beattie and Doktycz at Oak Ridge National Laboratory have pioneered work on novel, porous DNA chip materials, particularly capillary channel glass. The porous chips support increased hybridization reaction kinetics compared to flat chips. Protocols will be enhanced for production of chips, for hybridization of DNA targets to the chips, and for detection of the hybridized DNA. A number of novel polymorphism analysis methods that bypass the requirement for PCR amplification of hybridization targets will be explored. Instrumentation for chip arraying and reading will be improved. Finally, DNA chips for typing short insertion/deletion polymorphisms will be gradually introduced into the genotyping factory at Marshfield to supplement STRP typing in linkage analysis of disease genes.