High resolution DNA copy/LOH measurements on WGG arrays

WGG 阵列上的高分辨率 DNA 拷贝/LOH 测量

• 批准号: 6934807
• 负责人: KEVIN L GUNDERSON
• 金额: $ 58.4万
• 依托单位: ILLUMINA, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6934807
• 关键词: chromosome disorders; computer program /software; computer system design /evaluation; gene deletion mutation; genotype; human genetic material tag; human tissue; laser capture microdissection; loss of heterozygosity; neoplasm /cancer genetics; technology /technique development

DESCRIPTION (provided by applicant): Anomalies of the genome, such as congenital chromosomal imbalances, can be present from birth or can arise during cell division and lead to formation of cancer. Progression of cancer can be followed by monitoring changes in the genome. For instance, allelic deletions of tumor suppressor genes and amplifications of oncogenes are well known events in carcinogenesis. The primary goal of this project is to develop a high resolution array-based approach to detecting and monitoring changes in tumor samples. A secondary goal is to detect microdeletions and amplifications in congenital chromosomal disorders. The proposed work will focus on developing DNA copy and loss of heterozygosity (LOH) measurements using our novel whole genome genotyping (WGG) platform. The WGG technology was developed, in part, through phase I funding. Under phase I, we developed a whole genome amplification protocol and an arraybased primer extension assay that enabled direct readout of the genome - both copy number and genotypes. This development obviates the need for the original proposed complexity reduction step (reduced representation). The number of genotypes that can be read out from a single sample is limited only by the number of probes on the array. The proposed work will use a WGG array that is currently under development to perform genotyping and copy number analysis at the same time, at an average resolution of approximately 30 kb across the genome. This revolutionary assay system will allow regions of genomic alteration to be precisely defined accurately and robustly, and has the potential to be used directly in clinical applications. Once fully developed, the assay will be employed to characterize biological tumor/normal sample pairs as well as congenital chromosomal imbalances.

描述（由申请人提供）：基因组异常，如先天性染色体不平衡，可以从出生时就存在，也可以在细胞分裂期间出现，并导致癌症的形成。癌症的进展可以通过监测基因组的变化来跟踪。例如，肿瘤抑制基因的等位基因缺失和癌基因的扩增是癌发生中众所周知的事件。该项目的主要目标是开发一种基于高分辨率阵列的方法来检测和监测肿瘤样本的变化。第二个目标是检测先天性染色体疾病中的微缺失和扩增。拟议的工作将集中在开发DNA拷贝和杂合性丢失（洛）测量使用我们的新的全基因组基因分型（WGG）平台。WGG技术的开发部分是通过第一阶段的资金。在第一阶段，我们开发了一个全基因组扩增方案和一个基于阵列的引物延伸试验，使直接读出基因组-拷贝数和基因型。这种发展消除了对最初提出的复杂性降低步骤（减少表示）的需要。可以从单个样品中读出的基因型数量仅受阵列上探针数量的限制。拟议的工作将使用目前正在开发的WGG阵列同时进行基因分型和拷贝数分析，整个基因组的平均分辨率约为30 kb。这种革命性的检测系统将允许基因组改变的区域被精确地、准确地、鲁棒地定义，并且具有直接用于临床应用的潜力。一旦完全开发，该检测试剂盒将用于表征生物肿瘤/正常样本对以及先天性染色体失衡。