Biosensor Chip for Venous Thromboembolism Genotyping

描述（由申请人提供）：我们的假设是，导致静脉血栓栓塞风险的重要遗传因素尚未被确定，特别是在非裔美国人（AA）人群中。我们建议利用一种新型的、廉价的光学生物传感器检测方法，同时筛选样品中的多个单核苷酸多态性（snp）或indel（短插入/缺失）。Richard Marlar和Carolyn Welsh，以确定这些遗传因素。这些研究将使用患有遗传性血栓性疾病（HTD）的病例/对照人群（700例；1400例对照）和家庭（410例）。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性对静脉血栓栓塞风险的相对贡献进行统计评估。已报道的促成VTE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取代的snp将被分析。广泛的新基因数据集将被纳入与Marlar博士及其同事合作评估的获得性和生理性静脉血栓栓塞风险因素和集体风险参数的VA Merit Review研究中。我们建议对非裔美国人（AA）病例进行进一步的静脉血栓栓塞分析，包括来自HTD家族研究的34个AA家族的个体和来自病例/对照研究的AA个体。这些样本将通过混合制图进行分析，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，而在欧洲基因组中丰度较低或不存在。接下来将分析AA VTE家族和病例/对照研究中AA个体的VTE相关基因单倍型。

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.