National Biological Sample and Data Repository for PAH

描述（由申请人提供）：这是一项研究者发起的资源相关研究项目申请（R24），旨在为世界卫生组织（WHO） 1组肺动脉高压（PAH）患者创建生物样本和遗传数据的生物库。一旦建立，这一国家资源将大大加强对这一毁灭性和致命疾病的基础、转化和临床研究。收集的生物样本和从这些样本中产生的遗传数据将使前所未有的假设驱动的科学成为可能，迄今为止，这在多环芳烃或其他形式的肺动脉高压中是不可能的。国家多环芳烃生物样本和数据储存库将代表全美学术PH中心之间前所未有的合作，其努力将导致国内或国际上最大的多环芳烃患者队列的收集。由此产生的患者队列和数据可以为tour de force研究工作提供急需的催化剂，旨在通过识别导致该疾病的新途径或遗传因素来加速新疗法的开发。无可否认，该资源库满足了国家需求，实现了NHLBI的战略愿景，并为更广泛的科学界提供了真正独特的资源。为了建立这一国家资源，我们建议：1)与美国多环芳烃学术中心合作，收集和维护不少于2500名WHO 1组多环芳烃患者的生物材料。每个患者的样本包括基因组淋巴细胞DNA、EBV转化的外周血淋巴细胞和血浆；2)生成2500例入库患者全基因组SNP基因型数据和BMPR2/ALK1序列/MLPA数据。SNP数据将在其沉积在基因型和表型数据库（dbGaP）之前进行“清洗”；3)广泛推广和分发国家多环芳烃生物样本和数据库中保存的样本和基因型/序列数据。所有生物样本、临床数据以及患者的SNP基因型和测序数据将向科学界提供。

DESCRIPTION (provided by applicant): This is an Investigator-Initiated Resource-Related Research Project Application (R24) to create a biorepository of both biological samples and genetic data for patients with World Health Organization (WHO) Group 1 pulmonary arterial hypertension (PAH). Once established, this national resource will significantly enhance the conduct of basic, translational, and clinical research for this devastating and lethal disorder. The biological samples collected and genetic data generated from these samples will enable unprecedented hypothesis-driven science which to date has not been possible for PAH or other forms of pulmonary hypertension. The National Biological Sample and Data Repository for PAH will represent an unprecedented collaboration between academic PH centers across the United States whose efforts will lead to the collection of the largest cohort of PAH patients either nationally or internationally. The resulting cohort of patients and data can provide the much needed catalyst for tour de force research efforts aimed at accelerating the development of novel therapies through the identification of novel pathways or genetic factors contributing to the disorder. This repository undeniably addresses a national need that fulfills the strategic vision of NHLBI and provides truly unique resources to the broader scientific community. To establish this national resource, we propose to: 1) Work with PAH academic centers in the United States to collect and maintain biological material from no less than 2500 WHO Group 1 PAH patients. Samples to be banked on each patient include total genomic lymphocyte DNA, EBV transformed peripheral blood lymphocytes, and plasma; 2) Generate both genome wide SNP genotype data and BMPR2/ALK1 sequence/MLPA data on 2500 patients enrolled in the bank. The SNP data will be "cleaned" prior to its deposition in the database of Genotypes and Phenotypes (dbGaP); 3) Widely promote and distribute samples and genotype/sequence data maintained at the National Biological Sample and Data Repository for PAH. All biological samples, clinical data, as well as the SNP genotype and sequencing data for the patients will be made available to the scientific community.