Comparative toxicogenomics to determine conserved genetic and environmental interactions in craniofacial birth defects

项目摘要 颅面畸形是人类最常见的先天缺陷之一。的多因素基 人类先天缺陷阻碍了对罪魁祸首基因和毒物的识别。环境暴露 发生在混合物中，遗传变异可以使胚胎对这些混合物敏感。本提案使用 生物信息学和高通量分析用于预测和表征分娩过程中的多因素交互作用 使用斑马鱼和老鼠的缺陷。这项建议的目的是：(1)定义相互之间的协同作用 环境毒物；(2)基因-环境相互作用的模型和特征；(3)测试人类疾病 相关性和进化守恒。这种方法利用了我在斑马鱼和老鼠方面的专业知识 发展毒理学，快速有效地洞察最重要的未解答问题 围绕出生缺陷病因学。建议的研究将为通过风险进行预防提供直接途径 传播新的环境和遗传风险因素。

Project Summary Craniofacial dysmorphologies are among the most common human birth defects. The multifactorial basis of human birth defects has hindered identification of culpable genes and toxicants. Environmental exposures occur in mixtures, and genetic variation can sensitize embryos to these mixtures. This proposal uses bioinformatics and high-throughput analyses to predict and characterize multifactorial interactions in birth defects using zebrafish and mice. The aims of this proposal are: (1) Define synergistic interactions between environmental toxicants; (2) Model and characterize gene-environment interactions; (3) Test human disease relevance and evolutionary conservation. This approach leverages my expertise in zebrafish and mouse developmental toxicology to rapidly and efficiently gain insights into the most important unanswered questions surrounding birth defect etiology. The studies proposed will provide a direct avenue for prevention through risk communication of novel environmental and genetic risk factors.