Core C: Genetic Core

核心C：遗传核心

• 批准号: 8528333
• 负责人: MIIKKA S. VIKKULA
• 金额: $ 15.56万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8528333
• 关键词: Address; Behavior; Blood Vessels; Blood capillaries; Blood specimen; Boston; Candidate Disease Gene; Cell Culture Techniques; Cell Line; Cells; Clinical; Clinical Data; Collaborations; Collection; Complementary DNA; DNA; Data; Data Analyses; Database Management Systems; Databases; Disease; Endothelial Cells; Evaluation; Family; Family member; Functional disorder; Future; Genetic; Genomics; Goals; Hemangioma; Human Herpesvirus 4; Inborn Genetic Diseases; Inheritance Patterns; Inherited; Instruction; Link; Measures; Molecular; Mutation; Pathway interactions; Patients; Penetrance; Play; Prevalence; Proteins; Publications; Questionnaires; RNA; Research Personnel; Resources; Role; Sampling; Somatic Mutation; TEK gene; Tissue Sample; Tissues; Venous Hemangioma; Venous Malformation; Venous blood sampling; Work; base; capillary; genetic analysis; genetic pedigree; indexing; interest; lymphoblast; malformation; novel diagnostics; programs; research study; sample collection; screening

The goal of this Core is to provide DNA, RNA, protein and tissue samples, as well as lymphoblasts, from vascular anomaly patients. In addition, this Core will isolate endothelial cells and non-endothelial cells (mural cells) from hemangiomas and venous anomalies. These samples and cell lines will be used in the analyses related to all three projects of this Program Project. In addition, the Core collects clinical information and pedigree data pertinent to the samples. This data is essential not only for the genetic approaches (Projects 1 and 3), but also when analysing tissues or cell lines for differential expression, somatic mutations or altered behaviour in cell culture in vascular anomaly subtypes (Projects 1, 2, and 3). The sample collection will also ultimately serve for fast and efficient screening of newly identified candidate genes in a well-characterized sample set. The work of Core C is largely based on the extensive collaborative work and expertise of Dr J.B. Mulliken, Vascular Anomalies Center, Boston and Dr LM Boon, Vascular Anomalies Center, Brussels. This collaboration has led to numerous clinical publications describing novel diagnostic measures, prevalence and treatment of vascular anomalies. In addition, in collaboration with Drs Vikkula and Olsen, genetic background has been elucidated for certain forms. For example, due to this tight collaboration, the two teams newly recognised an inherited disorder characterized by atypical capillary malformations associated with fast- flow vascular anomalies (CM-AVM). Using the samples collected by Core C, Project 3 also recently discovered that 49% of sporadic venous malformations are due to somatic hyperphosphorylating TIE2 mutations. Moreover, in collaboration with Project 2 and 3, Project 1 led to the discovery of genetic alterations that play an important role in hemangioma pathophysiology, using samples of this Core. Core C has collected 897 famiUes, 1795 blood samples, 515 tissue samples, and established 135 cell lines. This unique collection of well-characterized samples will be enlarged continuously throughout the Program Project. This allows access of all three Projects of this Program Project to sufficient numbers of samples that are essential for achieving their Aims. RELEVANCE (See instructions): This project aims to collect blood and tissue samples and derive cell-lines from them, from well-characterized patients with vascular anomalies, also known as "angiomas". Such a resource enables efficient research studies to identify the causes of these disorders. Therefore, more specific, better, treatments can be developed in the future.

该核心的目标是提供DNA，RNA，蛋白质和组织样本，以及淋巴母细胞， 血管畸形患者。此外，该核心将分离内皮细胞和非内皮细胞（壁细胞）。 细胞）从血管瘤和静脉异常。这些样本和细胞系将用于分析 这三个项目都与本项目有关。此外，核心还收集临床信息， 与样本相关的谱系数据。这些数据不仅对遗传学方法（项目1）至关重要， 和3），而且当分析组织或细胞系的差异表达、体细胞突变或改变时， 血管异常亚型细胞培养中的行为（项目1、2和3）。样本采集还将 最终用于在良好表征的基因组中快速有效地筛选新鉴定的候选基因。 样本集核心C的工作主要基于J.B.博士的广泛协作和专业知识。 Mulliken，波士顿血管异常中心和LM布恩博士，布鲁塞尔血管异常中心。这 合作导致了许多临床出版物，描述了新的诊断措施，患病率和 治疗血管异常。此外，与Vikkula博士和Olsen博士合作， 已经针对某些形式阐述了背景技术。例如，由于这种紧密的合作，两个团队 新发现的一种遗传性疾病，其特征为与快速- 血流血管异常（CM-AVM）。利用核心C收集的样本，项目3最近还 发现49%的散发性静脉畸形是由于体细胞过度磷酸化TIE 2 突变。此外，与项目2和项目3合作，项目1导致发现了遗传 在血管瘤病理生理学中起重要作用的改变，使用本核心样本。 核心C收集了897个家系，1795份血液样本，515份组织样本，建立了135个细胞系。 在整个项目期间，这一独特的、具有良好特征的样品集将不断扩大 项目这允许本计划项目的所有三个项目访问足够数量的样本， 对于实现其目标至关重要。 相关性（参见说明）： 该项目旨在收集血液和组织样本，并从中获得细胞系， 患有血管异常的患者，也称为“血管瘤”。这样的资源可以进行有效的研究 研究以确定这些疾病的原因。因此，更具体，更好的治疗方法可以 在未来发展。