Identification of genetic susceptibility to thrombosis i

临床基因组学实验室的任务之一是为医生提供在人类疾病研究中应用基因组和遗传学方法的培训。与这一目标相关的是我们试图设计全球方法来识别和筛选复杂疾病的风险因素。为此，我们设计了一种基于杂交的高通量方法，用于筛选血栓形成的易感危险因素。 血栓形成被认为在大脑假瘤的发生中起一定作用。静脉血栓每年每1000人中就有1人受到影响，是死亡和发病的主要原因之一，仅在美国每年就导致约30万人住院和50000人死亡。然而，如果实行目前可用的预防性治疗，它是一种可以避免的疾病。我们的计算表明，同时使用10项基因检测可以使静脉血栓检测的阳性预测值增加至少25倍。我们已经设计了一种方法(为识别血栓形成[MERT]而发展的方法，正在申请专利)，它将通过快速、同时筛选8个不同基因中所有已知的143个静脉血栓相关的反复突变和多态来预测和准确评估几个种族群体的遗传性血栓形成，以便为风险适应预防制定分层方案。初步研究取得了积极的结果。我们正在验证所制造的微阵列的临床适用性。

One of the missions of the Laboratory of Clinical Genomics is to provide training to physicians in the application of genomic and genetic approaches in the studies of human diseases. Relevant to this goal is our attempts to device global approaches in the identification and screening of risk factors of complex disorders. To this end we have designed a hybridization-based high throughput method for screening of susceptible risk factors for thrombophilia. Thrombosis is suggested to play a role in the development pseudotumor cerebri. Venous thrombosis affects 1 per 1000 individuals annually and is one of the leading causes of mortality and morbidity resulting in approximately 300,000 hospitalizations and 50,000 fatalities per year in the United States alone. It is, however, an avoidable disease if currently available prophylactic treatment is instituted. Our calculations demonstrated that concurrent use of a panel of 10 genetic tests increases the positive predictive value of testing for venous thrombosis at least 25 fold. We have devised an approach (Method Evolved for Recognition of Thrombophilia [MERT], patent pending) that will allow prediction and accurate assessment of hereditary thrombophilia in several ethnic populations by rapid, concurrent screening of an array of all known 143 venous thrombosis associated recurrent mutations and polymorphisms in 8 different genes in order to develop stratification protocols for risk-adapted prophylaxis. Positive results were obtained in preliminary studies. We are in the process of verifying the clinical applicability of the fabricated microarrays.