Intermountain West Clinical Center for a Childhood Liver Disease Research Network

项目摘要 我们的目标是继续Intermountain West儿童肝病研究临床中心 网络（ChiLDReN）在犹他州和小学儿童医院的大学。在过去的融资中 周期，我们招募并保留了大量的参与者，实现了出色的网站性能， 并以高度协作的方式参与网络的所有活动。此外，在此前的 在资金周期内，我们转移、比对和处理DNA序列，以支持所有网络基因组学 努力，并提供了基础设施，通过网络与网络调查人员共享这些序列数据， 基于密码保护的软件工具。在目标1中，我们将继续招募婴儿、儿童和 在当前和未来的ChiLDReN方案中，青少年将继续提交有价值的生物样本， 准确和及时的数据，并协同参与所有网络活动。在目标2中，我们建议测试 胆道闭锁新生儿筛查计划在大型综合医疗保健系统中的可行性， 每年约30，000次交付。该医疗保健系统中的所有新生儿均已接受总血清胆红素检查 筛查作为标准护理的一部分。我们会在目的2中加入一项先导研究，以量度对母亲的影响 采用病例对照重复测量研究设计，在 目的3：对10名参与者及其父母进行全基因组测序， 测序未能确定分子诊断。为了实现这一目标，网络调查人员将与 使用犹他大学开发的基于网络的工具选择受试者进行全基因组测序。这些 这些工具不需要生物信息学专业知识，并且能够进行专家级的全网络中心基因组审查。 作为一个高度合作的儿童健康中心，实现拟议的目标将带来新的知识 关于儿童肝脏疾病的生物化学，生理学和机制，并改善 诊断和管理的选择与他们的孩子受苦。

PROJECT SUMMARY ABSTRACT Our goal is to continue the Intermountain West Clinical Center for the Childhood Liver Disease Research Network (ChiLDReN) at the University of Utah and Primary Children's Hospital. During the previous funding cycle, we enrolled and retained a significant number of participants, achieved outstanding site performance, and participated in a highly collaborative manner in all Network activities. Additionally, during the previous funding cycle, we transferred, aligned, and processed DNA sequences in support of all Network genomics efforts, and provided the infrastructure to share these sequence data with Network investigators via web- based, password protected software tools. In Aim 1, we will continue to enroll infants, children, and adolescents in current and future ChiLDReN protocols, continue to submit valuable biological specimens and accurate and timely data, and collaboratively participate in all Network activities. In Aim 2, we propose to test the feasibility of a biliary atresia newborn screening program in a large integrated healthcare system covering ~30,000 deliveries per year. All newborns in this healthcare system already undergo total serum bilirubin screening as part of standard of care. We will embed a pilot study in Aim 2 to measure the impact on mothers of newborns with a false positive newborn screen using a case-control repeated measures study design. In Aim 3, we will perform whole genome sequencing on 10 participants and their parents in whom exome sequencing failed to identify a molecular diagnosis. For this Aim, Network investigators will collaboratively select subjects for whole genome sequencing using University of Utah-developed web-based tools. These tools require no bioinformatic expertise and enable expert, Network-wide central genome review. Accomplishing the proposed aims as a highly collaborative Center for ChiLDReN will lead to new knowledge regarding the biochemistry, physiology, and mechanisms of childhood liver diseases, and improve the diagnostic and management options for children afflicted with them.