Orofacial Clefts, Whole Genome Sequencing and Incidental Findings: Ethical considerations

口面部裂痕、全基因组测序和偶然发现：伦理考虑

基本信息

批准号：
10217501
负责人：
Azeez Butali
金额：
$ 15.7万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-06 至 2021-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10217501
关键词：
Adult Affect Affinity Africa Africa South of the Sahara African Alkanesulfonates Alleles Architecture Asians Bilateral Binding Biological Birth Canada Candidate Disease Gene Caring Cell Line Cells Child Chromatin Cleft Palate Cleft lip with or without cleft palate Code Collaborations Craniofacial Abnormalities Data Disease Embryo Embryonic Development Engineering Enhancers Environmental Risk Factor Enzymes Ethanol Ethics Etiology Europe European Family Folic Acid Gene Frequency Genes Genetic Genetic Risk Genetic study Genomics Genotype Goals HepG2 Hepatocyte Immigration Incidental Findings Individual Infant Infrastructure Iowa Knowledge Lead Link Liver MSX1 gene Measures Medical Meta-Analysis Metabolism Minor Modification Mutation National Human Genome Research Institute Nigerian Outcome Parents Pathogenesis Pathway interactions Patients Persons Phenotype Population Predictive Factor Prevention Publishing Reporter Reporting Research Risk Role Single Nucleotide Polymorphism Societies Specificity Steroids Testing Tissues Translating Triad Acrylic Resin United States Universities Untranslated RNA Variant Vitamin D Work Zebrafish base cell type chromatin immunoprecipitation cleft lip and palate clinical practice cost craniofacial development de novo mutation design effective intervention genetic variant genome sequencing genome wide association study genome-wide genome-wide analysis high risk in vitro Assay insight novel orofacial cleft proband promoter psychologic rare variant risk variant transcription factor whole genome

项目摘要

PROJECT SUMMARY The focus of this study is to identify meaningful genetic and genomic factors that predict cleft outcomes in families in the African population, translate findings to other populations in order to design strategies towards reducing the outcome and prevention of CLP. We plan to replicate African GWAS significant loci in 1000 CL/P cases, 400 CP and 2000 controls by genotyping 172 single nucleotide polymorphisms. We also plan to conduct whole genome sequencing of 300 triads (proband with bilateral complete cleft lip and palate) and analyses whole genome sequencing (WGS) data of 150 CL/P triads. Finally, we plan to determine the functional consequences of GWAS non-coding variants by systematically testing SNPs with strongest disease association. This study will be led by Dr Butali at the University of Iowa in collaboration with Dr Cornell, Dr Murray and Dr Cao at the University of Iowa, Dr Adeyemo at the NHGRI and Dr Taub at the John Hopkins University.

项目概要这项研究的重点是确定预测唇裂的有意义的遗传和基因组因素非洲人口家庭的结果，将研究结果转化为其他人群，以便设计减少 CLP 后果和预防的策略。我们计划复制通过基因分型确定 1000 个 CL/P 病例、400 个 CP 和 2000 个对照中的非洲 GWAS 显着位点 172 单核苷酸多态性。我们还计划对300个样本进行全基因组测序三联症（双侧完全性唇腭裂先证者）并分析全基因组 150 个 CL/P 三联体的测序 (WGS) 数据。最后，我们计划确定功能通过系统测试最强的 SNP 来分析 GWAS 非编码变异的后果疾病协会。这项研究将由爱荷华大学的 Butali 博士合作领导与爱荷华大学的康奈尔博士、Murray 博士和曹博士、NHGRI 的 Adeyemo 博士以及约翰·霍普金斯大学的陶布博士。