Analysis of Whole Genome Sequencing Data From an Infantile Hemangioma Syndrome Cohort

婴儿血管瘤综合征队列的全基因组测序数据分析

• 批准号: 9921445
• 负责人: Dawn H. Siegel
• 金额: $ 16.04万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9921445
• 关键词: 3-Dimensional; Address; Affect; Aortic coarctation; Arteries; Award; Benign; Bioinformatics; Biological Process; Biology; Blindness; Blood Vessels; Brain; Cancer Etiology; Cervical; Child; Congenital Abnormality; DNA Sequence Alteration; Dandy-Walker Syndrome; Data; Databases; Development; Diagnosis; Distress; Endothelial Cells; Epigenetic Process; Eye; Eyelid structure; Face; Family; Fibroblasts; Financial Hardship; Gene Expression; Genes; Genetic; Genetic Diseases; Genetic Predisposition to Disease; Genome; Genomics; Goals; Healthcare Systems; Hearing; Heart; Heart Abnormalities; Hemangioma; Individual; Infant; International; Joints; Knowledge; Lead; Link; Malignant Childhood Neoplasm; Morbidity - disease rate; Neoplasms in Vascular Tissue; Newborn Infant; Organ; PHACE syndrome; PIK3CA gene; Parents; Pathogenesis; Pathway interactions; Pediatric Research; Pericytes; Phenotype; Posterior Fossa; Prevention strategy; Public Health; Recurrence; Registries; Resources; Risk; Scalp structure; Single Nucleotide Polymorphism; Strawberry nevus; Structural Congenital Anomalies; Structure; Syndrome; Testing; Tumor Suppressor Genes; Variant; Vision; acronyms; arterial tortuosity; body system; brain malformation; cancer genetics; clinical phenotype; cohort; congenital heart disorder; data resource; deafness; epigenetic regulation; genetic architecture; genetic variant; genome sequencing; genomic data; human data; improved; infancy; innovation; mortality; next generation sequencing; novel therapeutics; phenotypic data; prevent; programs; recruit; stroke risk; surgical risk; targeted treatment; whole genome

PROJECT SUMMARY Infantile hemangiomas are the most common benign vascular tumor in infants, affecting 4-5% of children. Thirty percent of segmental infantile hemangiomas on the face and scalp are associated with birth defects of multiple organs. This condition is known as PHACE, an acronym for posterior fossa brain malformations, segmental facial hemangiomas, arterial anomalies, cardiac defects, eye anomalies, and sternal clefting. There is high morbidity associated with PHACE including risk to vision, congenital heart disease often requiring surgery, risk of stroke, deafness and neurodevelopmental delays. The hemangioma is a vascular tumor that requires treatment in infancy to prevent functional complications and disfigurement, but later undergoes involution. Our strategy is to use this highly valuable PHACE cohort to discover critical genes related to structural birth defects which will be a valuable resource to link multiple different projects in the Kids First Program. In Aim 1 we will analyze WGS to identify de novo genomic features in PHACE including single nucleotide variants, INDELS, copy number alterations, and structural variants. We then will use publicly available genome structural, epigenetic regulation, and gene expression data to identify epigenetic associations. In Aim 2 we will identify biologic processes affected by multiple different genomic variants for each major structural birth defect phenotype of PHACE. We will next use the Kids First Data Resource to integrate genomic and phenotypic data from a broad range of publicly available cohort databases to identify genetic pathways that are common to both PHACE and other childhood cancer and structural birth defect cohorts.

项目概要 婴儿血管瘤是婴儿最常见的良性血管肿瘤，影响4-5%的婴儿 孩子们。面部和头皮上 30% 的节段性婴儿血管瘤与此相关 患有多器官出生缺陷。这种情况被称为 PHACE，是后验的缩写。 脑窝畸形、节段性面部血管瘤、动脉异常、心脏缺陷、眼睛 异常和胸骨裂。 PHACE 的发病率很高，包括以下风险： 视力、通常需要手术的先天性心脏病、中风、耳聋和 神经发育迟缓。血管瘤是一种血管肿瘤，需要在婴儿期进行治疗 以防止功能性并发症和毁容，但随后会发生复旧。我们的策略是 利用这个非常有价值的 PHACE 队列来发现与结构性出生缺陷相关的关键基因 这将是链接“儿童优先”计划中多个不同项目的宝贵资源。目标 1 我们将分析 WGS 以识别 PHACE 中的从头基因组特征，包括单核苷酸 变异、INDELS、拷贝数改变和结构变异。然后我们将使用公开的 基因组结构、表观遗传调控和基因表达数据来识别表观遗传 协会。在目标 2 中，我们将识别受多种不同基因组影响的生物过程 PHACE 每种主要结构性出生缺陷表型的变体。接下来我们将使用 Kids First 数据资源，用于整合来自广泛公开可用的基因组和表型数据 队列数据库，用于识别 PHACE 和其他童年时期共有的遗传途径 癌症和结构性出生缺陷队列。