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.

项目摘要 婴儿血管瘤是婴儿中最常见的良性血管肿瘤， 孩子面部和头皮上30%的节段性婴儿血管瘤与 多个器官的先天缺陷这种情况被称为PHACE，是后 颅窝畸形，面部节段性血管瘤，动脉异常，心脏缺陷，眼 畸形和胸骨裂与PHACE相关的发病率较高，包括以下风险： 视力、先天性心脏病（通常需要手术）、中风风险、耳聋和 神经发育迟缓血管瘤是一种血管肿瘤，需要在婴儿期治疗 以防止功能性并发症和毁容，但后来经历复旧。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， 这将是一个宝贵的资源，以连接多个不同的项目在儿童第一计划。目标1 我们将分析WGS以鉴定PHACE中的从头基因组特征，包括单核苷酸 变体、INDELS、拷贝数改变和结构变体。然后我们将使用公开可用的 基因组结构，表观遗传调控和基因表达数据，以确定表观遗传 协会.在目标2中，我们将确定受多种不同基因组影响的生物过程。 PHACE的每个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，整合来自广泛的公开可用的基因组和表型数据 队列数据库可识别PHACE和其他儿童时期常见的遗传途径 癌症和结构性出生缺陷队列。