Biosensor Chip for Venous Thromboembolism Genotyping

描述（由申请人提供）：我们的假设是，尚未确定导致VTE风险的重要遗传因素，特别是在非洲裔美国人（AA）人群中。 我们建议利用一种新的，廉价的光学生物传感器检测筛选多个单核苷酸多态性（SNP）或插入/缺失（短插入/缺失），同时通过与理查德·马拉和卡罗琳·威尔士博士合作提供的样品，以确定这样的遗传因素。 这些研究将使用遗传性血栓性疾病（HTD）的病例/对照人群（700例; 1，400例对照）和家族（410例）。 我们的生物统计学家赵洪宇博士将对同时遗传的单个或多个多态性对VTE风险的相对贡献进行统计学评估。 将分析已报告导致VTE的SNP，以及启动子区或在凝血稳态相关基因中产生非保守氨基酸取代的SNP。 广泛的新遗传数据集将被纳入与Marlar博士及其同事合作评估的获得性和生理性VTE风险因素和集体风险参数的VA Merit Review研究中。 我们建议将更多的工作集中在非洲裔美国人（AA）的情况下，无论是个人从34个AA家庭的HTD家庭研究和AA个人的情况下/对照研究的VTE分析。 将通过混合作图分析这些样品，以鉴定含有存在于非洲基因组中且在欧洲基因组中丰度较低或不存在的疾病相关等位基因的基因组区域。 随后将分析病例/对照研究中AA VTE家族和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.