ANALYSIS OF CUSHING DISEASE WHOLE EXOME SEQUENCING DATA 2020

2020 年库欣病全外显子组测序数据分析

• 批准号: 10270238
• 负责人: MICHAEL TSAI
• 金额: $ 28.09万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-24 至 2023-09-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10270238
• 关键词: Adrenal Glands; Area; Bioinformatics; Clinical; Code; Collaborations; Copy Number Polymorphism; Corticotropin; Data; Disease; Endocrine; Face; Genetic; Genetic Code; Height; Hydrocortisone; Intramural Research; Knowledge; Laboratories; Length; Literature; Medical; Methods; Nose; Outcome; Paper; Patients; Pituitary Gland; Pituitary Neoplasms; Pituitary-dependent Cushing' s disease; Proteins; Publications; Publishing; Research; Technology; United States National Institutes of Health; Variant; Work; clinical center; cost effective; exome sequencing; expectation; genetic variant; interest; population health; stem

Cushing's disease (CD) is a condition in which the pituitary gland produces inappropriate levels of adrenocorticotropic hormone (ACTH). ACTH stimulates the adrenal gland to produce excess cortisol, leading to clinical disease. CD is commonly caused by ACTH secreting pituitary tumors. It is noteworthy that patients who have CD also have abnormal features including abnormal facial height and nasal length. Stemming from our work in CD, we have developed an interest in other pituitary and endocrine conditions which requires the same work as indicated for CD below. This collaboration has been very successful in producing important discoveries now published in the medical literature. The Division of Intramural Population Health Research (DIPHR) and the Division of Intramural Research (DIR) have been collaborating in the search for genetic variants associated with CD via whole exome sequencing (WES). WES is an efficient, cost effective method to interrogate the genetic code responsible for coding proteins. With the use of WES technology in the studying of the Cushing disease a large amount of data was generated for analysis. The work has been highly productive and made possible the publication of 6 papers to date in this area. With the large number of variants discovered in this study far exceeding the original expectation and comparison to controls, we continue to enhance our search for copy number variants. This task order will continue to expand our knowledge of CD by analyzing the WES data on CD and other cases in collaboration with Dr. Constantine Stratakis at the NIH clinical center. Cases will be selected from those with the best associated clinical and laboratory data.

库欣病 (CD) 是一种垂体产生不适当水平的 促肾上腺皮质激素（ACTH）。 ACTH 刺激肾上腺产生过量的皮质醇， 导致临床疾病。 CD通常是由分泌ACTH的垂体肿瘤引起的。这是 值得注意的是，CD 患者也有异常特征，包括面部高度异常 和鼻长。 由于我们在 CD 方面的工作，我们对其他垂体产生了兴趣 和内分泌条件，需要与下面针对 CD 所示的相同的工作。 这 合作非常成功地产生了重要发现，现已发表在 医学文献。 校内人口健康研究部 (DIPHR) 和校内部 Research (DIR) 一直在合作寻找与 CD 相关的遗传变异 全外显子组测序（WES）。 WES 是一种高效、经济的方法来询问 遗传密码负责编码蛋白质。 随着WES技术在库欣病研究中的应用，获得了大量数据 生成用于分析。 这项工作卓有成效，使 6 本书得以出版 迄今为止该领域的论文。随着这项研究迄今为止发现的大量变异 超出最初的预期并与对照进行比较，我们继续加强我们的搜索 对于拷贝数变体。 该任务订单将通过分析 CD 上的 WES 数据来继续扩展我们对 CD 的了解， 与 NIH 临床中心的 Constantine Stratakis 博士合作的其他病例。 案件将 从具有最佳相关临床和实验室数据的那些中选择。