Molecular Analysis of Human Subtelomeric Rearrangements
人类亚端粒重排的分子分析
基本信息
- 批准号:7354822
- 负责人:
- 金额:$ 34.29万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-02-01 至 2009-01-31
- 项目状态:已结题
- 来源:
- 关键词:10pAffectAlagille SyndromeAtrial Heart Septal DefectsBiological AssayBlood VesselsCandidate Disease GeneCardiacChromosomal RearrangementChromosome BreakageChromosome DeletionChromosomesClassClinicalCollaborationsComplexCongenital Heart DefectsCountryCytogenetic AnalysisCytogeneticsDNADNA MarkersDNA SequenceDNA Sequence RearrangementDataDatabasesDefectDevelopmentDiagnosisDiagnosticDown SyndromeEmbryoFluorescent in Situ HybridizationG-BandingGenesGoalsHumanIncidenceIndividualInfantLaboratoriesLeadLungMapsMicrosatellite RepeatsMolecularMolecular AnalysisMolecular CytogeneticsMolecular ProbesMusMutateMutationP1 Bacteriophage Artificial ChromosomesParentsPatientsPatternPediatric HospitalsPhenotypePhiladelphiaProcessPulmonary artery structureRNAResearch PersonnelResolutionResourcesSamplingSourceStandards of Weights and MeasuresStructureSupravalvular aortic stenosisSyndromeTechnologyTestingTimeUpper armWilliams SyndromeXenopusbasecisplatin/cyclophosphamide/doxorubicin protocolclinical Diagnosisclinical phenotypecohortcongenital heart disorderdevelopmental diseasehuman diseaselymphoblastoid cell lineprobandsizestillbirthtelomere
项目摘要
Congenital heart disease affects approximately 1% of infants, with an incidence estimated at close to ten times that level among stillbirths. Heart defects are seen both as isolated findings and components of syndromes. Several chromosomal syndromes include heart defects as consistent parts of the phenotype. Examples of such syndromes include Down syndrome (AV canal defects), DiGeorge/velocardiofacial (conotruncal defects), Williams syndrome (supravalvular aortic stenosis, pulmonary vascular involvement), and Alagille syndrome (pulmonary artery defects). Identifying the specific genes involved in these and other
complex developmental disorders have contributed to our understanding of the molecular processes involved in cardiac development. Human telomeres and subtelomeres have a unique structure consisting of multiple classes of DNA sequence repeats, as well as single copy sequences. These unique sequence regions are highly gene rich and prone to breakage and rearrangement. Consequences of this chromosome breakage have been shown to result in human disease. The development of molecular probe sets that permit the analysis of the integrity
of the subtelomeric regions using fluorescence in situ hybridization (FISH) technology has recently advanced the clinical diagnosis of patients with these types of chromosomal rearrangements. Through the use of this testing we have identified over 40 cases of subtelomeric rearrangements. Twenty-five percent of these individuals have congenital heart defects. We have begun to molecularly characterize the deletion boundaries in those cases with a consistent finding of congenital heart defects (specifically chromosome 6p associated with atrial septal defects and pulmonary artery abnormalities, and 9q associated with conotruncal defects). We propose to study a cohort of patients with subtelomeric rearrangements and congenital heart defects, characterize their deletion boundaries, and identify genes within these deletions that are responsible for cardiac defects when mutated. We hypothesize that these studies will lead to the identification of genes responsible for normal cardiac development that when mutated will be responsible for both syndromic and isolated forms of congenital heart defects.
先天性心脏病影响大约1%的婴儿,估计死胎的发病率接近10倍。心脏缺陷被视为孤立的发现和综合征的组成部分。几种染色体综合征包括心脏缺陷作为表型的一致部分。此类综合征的实例包括唐氏综合征(AV管缺陷)、DiGeorge/velocardiofacial(圆锥动脉干缺陷)、威廉姆斯综合征(瓣上主动脉狭窄、肺血管受累)和Alagille综合征(肺动脉缺陷)。识别这些和其他相关的特定基因
复杂的发育障碍有助于我们理解心脏发育中涉及的分子过程。人类端粒和亚端粒具有由多个类别的DNA序列重复以及单拷贝序列组成的独特结构。这些独特的序列区域是高度基因丰富的,并且易于断裂和重排。这种染色体断裂的后果已被证明会导致人类疾病。分子探针组的发展,允许分析的完整性
利用荧光原位杂交(FISH)技术对亚端粒区域的研究,最近已经推进了这些类型染色体重排患者的临床诊断。通过使用这种测试,我们已经确定了超过40例亚端粒重排。这些人中有25%患有先天性心脏病。我们已经开始从分子水平上描述那些发现先天性心脏病的病例中缺失边界的特征(特别是与房间隔缺损和肺动脉畸形相关的染色体6p,以及与圆锥动脉干缺损相关的染色体9 q)。我们建议研究一组端粒下重排和先天性心脏缺陷的患者,描述其缺失边界,并确定这些缺失中突变时导致心脏缺陷的基因。我们假设,这些研究将导致识别基因负责正常的心脏发育,当突变将负责综合征和孤立形式的先天性心脏缺陷。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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IAN D. KRANTZ其他文献
IAN D. KRANTZ的其他文献
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{{ truncateString('IAN D. KRANTZ', 18)}}的其他基金
Advancing Child Health: Preparing the Next Generation of Pediatric Researchers
促进儿童健康:培养下一代儿科研究人员
- 批准号:
10613355 - 财政年份:2020
- 资助金额:
$ 34.29万 - 项目类别:
Genomic Diagnostics in Cornelia de Lange Syndrome, Related Diagnosis and Structural Birth Defects
Cornelia de Lange 综合征的基因组诊断、相关诊断和结构性出生缺陷
- 批准号:
9808671 - 财政年份:2019
- 资助金额:
$ 34.29万 - 项目类别:
Advancing Child Health: Preparing the Next Generation of Pediatric Researchers.
促进儿童健康:培养下一代儿科研究人员。
- 批准号:
8830125 - 财政年份:2015
- 资助金额:
$ 34.29万 - 项目类别:
Advancing Child Health: Preparing the Next Generation of Pediatric Researchers.
促进儿童健康:培养下一代儿科研究人员。
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9280625 - 财政年份:2015
- 资助金额:
$ 34.29万 - 项目类别:
NIPBL, Cohesin and Related Structural Birth Defects
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- 资助金额:
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A role for the CdLS gene NIPBL in HP1 gene silencing
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7356463 - 财政年份:2007
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$ 34.29万 - 项目类别:
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