Biosensor Chip for Venous Thromboembolism Genotyping

用于静脉血栓栓塞基因分型的生物传感器芯片

• 批准号: 7120547
• 负责人: DAVID C WARD
• 金额: $ 33.06万
• 依托单位: NEVADA CANCER INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-10 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7120547
• 关键词: African American; alleles; aminoacid; biosensor device; blood coagulation; caucasian American; family genetics; genetic mapping; genetic susceptibility; genome; genotype; high throughput technology; human data; polymerase chain reaction; racial /ethnic difference; single nucleotide polymorphism; thromboembolism

DESCRIPTION (provided by applicant): Our hypothesis is that important genetic factors that contribute to VTE risk have not yet been identified, particularly within the African American (AA) population. We propose to utilize a novel, inexpensive optical biosensor assay for screening multiple single nucleotide polymorphisms (SNPs) or Indels (short insertions/deletions) simultaneously in samples made available through collaboration with Drs. Richard Marlar and Carolyn Welsh in order to identify such genetic factors. Both a case/control population (700 cases; 1,400 controls) and families (410) with Hereditary Thrombolic Disorder (HTD) will be used in these studies. The relative contribution of individual or multiple polymorphisms inherited simultaneously on VTE risk will be statistically assessed by our biostatistician, Dr. Hongyu Zhao. SNPs that have been reported to contribute to VTE, and SNPs that are in promoter regions or create nonconservative amino acid substitutions in genes associated with coagulation homeostasis will be analyzed. The extensive set of new genetic data will be incorporated into the VA Merit Review study of acquired and physiological VTE risk factors and collective risk parameters assessed in collaboration with Dr. Marlar and his associates. We propose to focus additional work on analysis of VTE in African American (AA) cases, both individuals from the 34 AA families from the HTD family study and AA individuals from the case/control study. These samples will be analyzed by admixture mapping to identify genomic regions containing disease related alleles that are present in the African genome and of lower abundance or absent in the European. This will be followed by analysis of VTE associated gene haplotypes in the AA VTE families and AA individuals in the case/control study.

描述(由申请人提供)：我们的假设是，导致静脉血栓栓塞症风险的重要遗传因素尚未被识别，特别是在非裔美国人(AA)人群中。我们建议利用一种新的、廉价的光学生物传感器试验，在理查德·马拉博士和卡罗琳·威尔士博士合作提供的样本中同时筛选多个单核苷酸多态(SNPs)或插入/缺失(Short Insertion/Deles)，以确定这些遗传因素。这些研究将使用病例/对照人群(700例；1400名对照)和遗传性血栓障碍(HTD)家族(410名)。我们的生物统计学家赵宏宇博士将对同时遗传的个体或多个多态对静脉血栓栓塞症风险的相对贡献进行统计评估。已被报道与VTE有关的SNP，以及位于启动子区域或在与凝血稳态相关的基因中产生非保守氨基酸替换的SNPs将被分析。这组广泛的新基因数据将被纳入退伍军人事务部功绩回顾研究，该研究与Marlar博士及其同事合作，对获得性和生理性VTE风险因素和集体风险参数进行了评估。我们建议将更多的工作重点放在分析非裔美国人(AA)病例中，既有来自HTD家族研究的34个AA家族的个体，也包括来自病例/对照研究的AA个体。这些样本将通过混合作图进行分析，以确定包含疾病相关等位基因的基因组区域，这些等位基因存在于非洲基因组中，丰度较低或在欧洲不存在。随后将分析病例/对照研究中AA VTE家系和AA个体的VTE相关基因单倍型。