Whole Genome Sequencing for Orofacial Clefts, Incidental Findings and Role of Community Gatekeepers

项目概要： 口面裂（OFC）是人类最常见的先天性异常， 全球每700例活产。病因是多因素的，具有复杂的相互作用的遗传和 环境因素几种策略已被用于确定OFCs的遗传病因，这些策略包括： 包括连锁、全基因组关联研究（GWAS）和全基因组测序（WGS）。的 WGS数据的鲁棒性允许发现新的裂缝风险位点和候选基因，同时还提供 有机会确定与主要研究意图不同的“偶然发现”， 对研究参与者及其亲属的直接医疗影响。有证据表明， 来自家庭成员、朋友、社区成员、卫生保健工作者和受影响的父母， 与OFCs有关。最大限度地造福和公正的结果，在人口中有巨大的遗传 多样性尽管在遗传和基因组研究中代表性不足，但需要与几个人合作， 探索在这些地区行之有效的方法，包括社区参与。可用 有证据表明，守门人在非洲不同背景下的研究中具有影响力。但 关于遗传学和基因组学研究中守门人的作用的信息很少。拟议的研究目标 评估尼日利亚社区守门人的理解以及他们对沟通的看法 在离岸金融中心的背景下，偶然的遗传研究结果已经与污名化有关。这 将通过解决以下问题来实现（1）确定看门人对基因组风险的感受 信息，（2）探讨把关人对其成员接受偶然发现的意见 （3）评估宗教领袖参与参与和协作决策的可能性- 基因组研究的风险沟通。该项目将由Butali博士作为负责人推动 调查员他将与拉各斯大学的Odukoya博士和NHGRI的Adeyemo博士合作。 总的来说，我们预计这项研究将有助于提高人们对组学研究的认识， 他们是把关人，反过来，他们的影响力将提高公众对基因组研究的认识。

PROJECT SUMMARY: Orofacial clefts (OFCs) are some of the most common congenital anomalies in humans, affecting one out of every 700 live births globally. The etiology is multifactorial, with a complex interaction of genetic and environmental factors. Several strategies have been used to identify the genetic etiology of OFCs; these include Linkage, Genome-wide Association Studies (GWAS), and Whole Genome Sequencing (WGS). The robustness of WGS data allows the discovery of new cleft risk loci and candidate genes while also providing the opportunity to identify "incidental findings" different from the primary research intent that may have immediate medical implications for study participants and their relatives. Evidence suggests that stigmatization from family members, friends, community members, health-care workers, and the affected parents are associated with OFCs. Maximizing beneficence and justice from results in a population with vast genetic diversity albeit underrepresented in genetic and genomic research requires working with several people and exploring methods with proven success in these regions, including community engagement. Available evidence has shown gatekeepers to be influential in research across varying context in Africa. However, there is little information on the role of gatekeepers in genetics and genomics research. The proposed research aims to assess the understanding of community gatekeepers in Nigeria and their opinions on communicating incidental genetic research findings in the context of OFCs that is already associated with stigmatization. This will be achieved by addressing the following (1) determine the feelings of gatekeepers about genomic risk information, (2) explore the opinions of gatekeepers on the acceptance of incidental findings by their members and (3) evaluate the possibility of religious leaders' involvement in participatory and collaborative decision- making for genomic research risk communications. This project will be driven by Dr Butali as Principal Investigator. He will collaborate with Dr. Odukoya at the University of Lagos, and Dr. Adeyemo at the NHGRI. Collectively, we anticipate that this study will help create the awareness for omics research amongst the gatekeepers, who in turn from their point of influence will increase genomic research awareness in the public.