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Maternal alcohol exposure: impact on genetic control of craniofacial phenotype

母亲酒精暴露：对颅面表型遗传控制的影响

基本信息

批准号：
8884399
负责人：
Ali Murat Maga
金额：
$ 24.9万
依托单位：
SEATTLE CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8884399
关键词：
Address Adult Adverse effects Affect Alcohol consumption Alcohols Animal Model Award Backcrossings Bioinformatics Chromosome Mapping Chronic Clinical Research Communities Confounding Factors (Epidemiology)Consumption DNA Methylation Data Dentistry Development Developmental Gene Diagnosis Diagnostic Disease Dose Dysmorphology Embryo Embryology Environment Environmental Risk Factor Epigenetic Process Ethanol Event Exposure to Face Faculty Fetal Alcohol Spectrum Disorder Fetal Alcohol Syndrome Fetal Development Fetus Future Gender Gene Expression Gene-Modified Genes Genetic Genetic Variation Genomic Segment Genomics Goals Growth Health Human Image Imaging Techniques Lead Location Long-Term Effects Malnutrition Maps Maternal Age Measurable Mediating Medicine Methodology Methods Microarray Analysis Mind Modeling Modification Molecular Molecular Profiling Morphogenesis Morphology Mouse Strains Mus Optics Outcome Pathway interactions Perinatal Exposure Phase Phenotype Postdoctoral Fellow Pregnancy Quantitative Genetics Quantitative Trait Loci Race Reporting Research Research Infrastructure Research Personnel Resolution Role Science Shapes Skeleton Stress Techniques Testing Time Translating Uncertainty Universities Variant Washington alcohol effect alcohol exposure alcohol response base clinical practice craniofacial craniofacial development differential expression digital imaging dosage epigenome fetal fetal programming genetic variant improved in utero in vivo interest malformation medical schools member microCT mouse model news novel offspring pediatric department peer pre-clinical prevent programs quantitative imaging response skeletal skills tomography tool trait web interface

项目摘要

Project Summary I am a postdoctoral fellow in the Division of Craniofacial Medicine, Department of Pediatrics, University of Washington in Seattle. My research interests lie in understanding the mechanisms (ie. contributions of genes and environmental factors) responsible for human malformations, specifically craniofacial disorders, and normal phenotypic variation. With this in mind, my goal is to exploit tomographic imaging techniques as well as geometrics morphometrics as a means to quantitatively assess craniofacial phenotypes. I apply to this K99/R00 Pathways to Independence Award with the long-term goal becoming an independent researcher in the field of craniofacial dysmorphology. I have developed a research program to augment my background in quantitative morphology and 3D digital imaging with quantitative genetics and embryology to transition myself into an independent investigator in biomedical sciences. As the first step towards this goal, I will explore the effect of gestational alcohol exposure on the embryonic and post-natal craniofacial development of mice using: (1) state-of-the-art high-resolution in-vivo microCT and optical projection tomography, (2) traditional 3D shape quantification methods and a new 3D grid deformation methodology to characterize phenotypic differences, and (3) the use of a novel mouse model of moderate dose chronic ethanol exposure that produces FAS related measurable phenotypes in adults Long-term goals of this proposal are to (1) investigate the role of epigenetic programming in the presentation of alcohol-related malformations through detailed quantification of the craniofacial phenotype and (2) correlate genomic differences with these features to find epigenetically modified genes responsible for the phenotypic differences . In the future, these genes and the mechanism(s) by which they are modified in this model can be translated into clinical research and can offer the potential to find ways to better diagnose or even prevent or circumvent the negative effects of alcohol on fetal development. The role for epigenetic programming in alcohol-related phenotypes will be addressed through these specific aims: K1. To explore the effect of gestational alcohol exposure on embryonic craniofacial development: K2. To assess the impact of genetic variation on craniofacial development. R1. To characterize fetal craniofacial gene expression changes in response to gestational ethanol exposure R2. To explore the longitudinal effects of maternal alcohol consumption on post-natal craniofacial development R3. To develop a bioinformatics model infrastructure for making data and results from this proposal available. The University of Washington Schools of Medicine and Dentistry have over 1,800 full-time faculty members in 38 Departments, including 8 Nobel laureates. This year the UW Department of Pediatrics was ranked 6th by the US News and World Report among its peers.

项目摘要我是一名博士后研究员，在颅面医学部，儿科，大学华盛顿在西雅图。我的研究兴趣在于了解机制（即。基因贡献和环境因素）造成人类畸形，特别是颅面疾病，正常表型变异考虑到这一点，我的目标是利用断层成像技术以及几何形态测量学作为定量评估颅面表型的手段。我适用于此 K99/R00独立之路奖，长期目标是成为一名独立的研究人员，颅面畸形学领域。我已经开发了一个研究项目，定量形态学和3D数字成像与定量遗传学和胚胎学，成为生物医学领域的独立调查员作为实现这一目标的第一步，我将探讨妊娠期酒精暴露对小鼠胚胎和出生后颅面发育的影响： (1)最先进高分辨率体内microCT和光学投影断层扫描，（2）传统的3D形状量化方法和新的3D网格变形方法来表征表型差异，和（3）使用中等剂量慢性乙醇暴露的新型小鼠模型，其产生FAS相关的成人可测量表型该提案的长期目标是（1）调查表观遗传编程在以下表现中的作用：通过详细量化颅面表型的酒精相关畸形和（2）相关基因组差异与这些功能，以找到表观遗传修饰的基因负责的表型差异在未来，这些基因和它们在该模型中被修饰的机制可以被进一步研究。转化为临床研究，可以提供找到更好的诊断甚至预防方法的潜力，避免酒精对胎儿发育的负面影响。表观遗传编程在酒精相关的表型将通过这些具体目标来解决： K1探讨妊娠期酒精暴露对胚胎颅面发育的影响： K2评估遗传变异对颅面发育的影响。 R1描述妊娠期乙醇暴露对胎儿颅面基因表达的影响 R2.探讨母亲饮酒对出生后颅面发育的纵向影响 R3.开发生物信息学模型基础设施，以提供本提案的数据和结果。华盛顿大学医学院和牙科学院拥有超过1,800名全职教师， 38个部门，包括8名诺贝尔奖获得者。今年，华盛顿大学儿科系排名第六，《美国新闻与世界报道》