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The role of noncoding regulatory variants in orofacial clefts

非编码调控变异在口面部裂中的作用

基本信息

批准号：
10302874
负责人：
ELIZABETH JANE LESLIE
金额：
$ 15.65万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10302874
关键词：
3&apos Untranslated Regions Accounting Address Affect Architecture Atlases Biological Assay Biological Models Chromatin Code Collaborations Complex Congenital Abnormality Data Developmental Biology Disease Economics Elements Embryo Enhancers Environmental Exposure Environmental Risk Factor Etiology Face Family Gene Expression Gene Expression Regulation Genes Genetic Polymorphism Genetic Risk Genetic Variation Genetic study Genome Genomics Goals Heritability Heterogeneity Human Individual Inherited Knowledge Maps Medical Genetics Mendelian disorder MicroRNAs Mus Mutation Newborn Infant Nucleotides Parents Pathogenicity Pediatric Research Phenotype Prevention Prognosis Regulatory Element Research Research Design Resources Risk Risk Factors Role Source Structure Syndrome Testing Tissues Translating Untranslated RNA Variant Work clinical application cohort craniofacial craniofacial development craniofacial tissue empowered exome sequencing genetic architecture genetic risk factor genetic testing genetic variant genome sequencing genome wide association study genome-wide genomic locus human disease improved insight miRNA expression profiling orofacial cleft programs promoter rare variant social targeted sequencing trait transcriptome sequencing usability whole genome

项目摘要

PROJECT SUMMARY Orofacial clefts (OFCs) are the most common craniofacial birth defect in humans and are caused by multiple genetic and environmental risk factors. Elucidating the etiology of OFCs is critical not only for our knowledge of developmental biology and for how clefts arise, but ultimately for improved prevention, treatment, and prognosis for individuals affected by OFCs. Clinical applications of genome sequencing are growing, but the usability for OFCs is hindered by a substantial missing fraction of heritable risk and a poor understanding of how variants in non-coding regulatory elements contribute to OFC risk. These elements include (but are not limited to) enhancers, promoters, noncoding RNAs (e.g., microRNA), and topologically associated domain boundaries. Despite the mounting evidence that non-coding regulatory variants are important contributors to human disease, widespread analysis of such variants in OFCs has been limited by the lack of a large resource of whole genome sequences in individuals with OFCs and difficulties annotating craniofacial regulatory variants. In this proposal, we will take advantage of several recent initiatives that directly address these barriers by analyzing rare de novo, inherited, and structural variants from over 1,300 case-parent trios with OFCs sequenced through the Gabriella Miller Kids First Research Program. We will integrate these data with genomic atlases of chromatin profiling, microRNAs, and RNA-seq data generated from human and mouse craniofacial tissues. These analyses will provide key insights into the genetic architecture of OFCs and will reveal the full potential of WGS data for OFCs.

项目总结