A Toxicogenomic Approach to Human Neural Tube Defects

人类神经管缺陷的毒理学方法

• 批准号: 6997532
• 负责人: Anastasia L Wise
• 金额: $ 4.62万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-14 至 2006-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6997532
• 关键词: Caenorhabditis elegans; RNase protection assay; biotechnology; clinical research; congenital nervous system disorder; corn; disease /disorder etiology; environmental exposure; food contamination; functional /structural genomics; gene environment interaction; gene expression; gene expression profiling; genetic screening; genetic susceptibility; human genetic material tag; human subject; linkage mapping; microarray technology; mycotoxins; neural plate /tube; polymerase chain reaction; predoctoral investigator; single nucleotide polymorphism; statistics /biometry; toxicant screening

DESCRIPTION (provided by applicant): With neural tube defect (NTD) rates of up to 106 cases per 10,000 births (20:10,000 world average), Guatemala's NTD prevalence is among the highest in the world (Cifuentes 2002). As the predisposition to and development of NTDs is complex, with both environmental and hereditary factors implicated, it is hypothesized that the high prevalence of NTDs in Guatemala is due to interactions between an underlying genetic predisposition in association with a common environmental exposure, fumonisin. The NTD Collaborative Study's whole genome single nucleotide polymorphism (SNP) screen will be used as a starting point for linkage analysis and potential candidate gene investigation. To compliment this linkage analysis, the transcriptome of fumonisin exposed C. elegans will also be characterized through the use of microarray technology. Using the candidate genes detected in the whole genom e SNP screen and C. elegans studies, 100 simplex Guatemalan pedigrees will then be evaluated using fam ily-based association methods. Fumonisin exposure will also be looked at as a potential environmental risk factor using statistical methods to test for gene-environment interactions.

描述（由申请人提供）：危地马拉的NTD患病率是每10,000个出生（20：10,000世界平均）的神经管缺陷（NTD），最多106例（20：10,000世界平均），是世界上最高的（Cifuentes 2002）。由于NTD的倾向和发展是复杂的，因此环境和遗传因素都牵涉到涉及的环境和遗传因素，因此假设危地马拉中NTD的高流行率是由于与常见的环境暴露相关的潜在遗传倾向之间的相互作用是造成的。 NTD协作研究的整个基因组单核苷酸多态性（SNP）筛选将用作连锁分析和潜在候选基因研究的起点。为了补充这种连锁分析，烟素暴露的秀丽隐杆线虫的转录组也将通过使用微阵列技术来表征。使用在整个基因E SNP筛查和秀丽隐杆线虫研究中检测到的候选基因，然后将使用基于FAM ILY的关联方法评估100个单纯危地马拉血统。使用统计方法来测试基因环境相互作用的统计方法，还将将暴露于富穆诺菌素暴露为潜在的环境风险因素。