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

• 批准号: 8668191
• 负责人: Ali Murat Maga
• 金额: $ 23.9万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 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/8668191
• 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; Genomics; Goals; Growth; Health; Human; Image; Imaging Techniques; Lead; Location; Long-Term Effects; Malnutrition; Maps; Maternal Age; Measurable; Mediating; Medicine; Methodology; Methods; 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; digital imaging; dosage; epigenome; fetal; fetal programming; improved; in utero; in vivo; interest; malformation; medical schools; member; mouse development; mouse model; news; novel; offspring; pediatric department; peer; pre-clinical; prevent; programs; response; skeletal; skills; tomography; tool; trait; web interface

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.

项目总结