Molecular approaches to gene identification in congenital heart disease

先天性心脏病基因鉴定的分子方法

• 批准号: 7768339
• 负责人: Wendy K Chung
• 金额: $ 25.65万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7768339
• 关键词: Adult; Age; Aneuploidy; Animal Model; Benign; Blood; Candidate Disease Gene; Cardiac; Cessation of life; Child; Chromosome abnormality; Clinical; Congenital Abnormality; Copy Number Polymorphism; Cytogenetics; Databases; Defect; Development; Diagnosis; Diagnostic; Etiology; Family; Family history of; Family member; Frequencies; Gene Dosage; Gene Mutation; Genes; Genetic; Genetic Counseling; Genomics; Goals; Growth; Heart Transplantation; Human; Hypoplastic Left Heart Syndrome; Incidence; Instruction; Knowledge; Laboratories; Life; Live Birth; Location; Methods; Molecular; Mosaicism; Mutation; Nervous System Physiology; Neurocognitive; Oligonucleotide Microarrays; Outcome; Parents; Pathway interactions; Patients; Point Mutation; Principal Investigator; Recruitment Activity; Recurrence; Reproductive History; Resolution; Risk; Sampling; Screening procedure; Second Pregnancy Trimester; Sequence Analysis; Support Groups; Syndrome; Systemic disease; Tissues; base; congenital heart disorder; density; genome-wide; improved; malformation; novel; offspring; outcome forecast; prognostic; programs; prospective; reproductive; research study

DESCRIPTION (provided by applicant): Congenital heart disease (CHD) is the most common birth defect with an incidence of 1% of all live births. Many cytogenetic abnormalities have been associated with CHD, and evidence is accumulating that many developmental defects can result from small genomic alternations invisible at the cytogenetic level, resulting in changes in copy number of contiguous genes. We propose to identify genetic contributions to CHD by screening for changes in gene copy number, using genome-wide high resolution oligonucleotide microarrays. We will also screen for genetic mutations in candidate genes in intervals of segmental aneuploidies and in candidate genes identified molecular cardiac development pathways and through model organism screens in the Cardiac Genetics Consortium using high throughput sequencing and analysis of intragenic deletions/duplications using customized oligonucleotide microarrays. Our long-term goals are to define a set of novel genetic and genomic aberrations important in the etiology of CHD, to characterize new syndromes associated with CHD, and to develop improved methods of clinical genetic diagnostics for CHD. We believe this information will provide more accurate clinical prognostic information that can improve genetic counseling and assist families in accurately determining risk of recurrence and prognosis associated with CHD RELEVANCE (See instructions): As CHD is increasingly diagnosed within the second trimester prenatally and as adults with CHD are living to reproductive age, some of the most critical clinical questions for prospective parents are whether or not the CHD in their family has an underlying genetic basis, quantifying the risk of recurrence, and determining prognosis including predictions of neurological function and systemic disease.

描述（由申请人提供）： 先天性心脏病 (CHD) 是最常见的出生缺陷，发病率占所有活产婴儿的 1%。许多细胞遗传学异常与先天性心脏病有关，并且越来越多的证据表明，许多发育缺陷可能是由细胞遗传学水平上不可见的微小基因组改变引起的，从而导致邻近基因拷贝数的变化。我们建议通过使用全基因组高分辨率寡核苷酸微阵列筛选基因拷贝数的变化来确定对先心病的遗传贡献。我们还将在节段性非整倍体间隔中筛选候选基因中的基因突变，以及在分子心脏发育途径中确定的候选基因中筛选基因突变，并通过心脏遗传学联盟中的模型生物筛选，使用高通量测序和使用定制寡核苷酸微阵列进行基因内删除/重复分析。我们的长期目标是定义一组在 CHD 病因学中重要的新型遗传和基因组畸变，表征与 CHD 相关的新综合征，并开发改进的 CHD 临床遗传诊断方法。我们相信这些信息将提供更准确的临床预后信息，从而改善遗传咨询并帮助家庭准确确定与 CHD 相关的复发风险和预后（参见说明）：随着 CHD 在产前妊娠中期和成年后越来越多地被诊断出来，冠心病在育龄期，对于准父母来说最关键的一些临床问题是其家族中的冠心病是否有潜在的遗传基础、量化复发风险以及确定预后，包括预测神经功能和全身功能。 疾病。