Genomic medicine and gene function implementation for an underserved population

项目摘要 在这里，我们建议推进NHGRI的目标，以实现基因组医学，并专注于个人 他们负担不起DNA检测的费用这项研究发生在分子和 贝勒医学院（Baylor College of Medicine）和德克萨斯儿童医院（Texas Children Hospital）的人类遗传学。我们的团队的 临床医生，遗传学家，计算机科学家，基因组学家和模式生物研究人员已经进行了为期五年的 未诊断疾病网络（UDN）模式生物筛选中心（MOSC）的成功术语。 这包括成功鉴定了许多新的疾病基因，如EBF 3、IRF 2BPL、NACC 1、 TBX 2、TOMM 70、CDK 19、ACOX 1、WDR 37和ATP 5 F1 D。我们建议从一个 得克萨斯州休斯顿的服务不足人口患有疑似罕见疾病，无法支付 DNA测序通过保险我们将提供全外显子组测序，这将产生CAP/CLIA 我们预计每年可以诊断35-40人。剩下的人将 转化为基于家族的三人外显子组设计。该项目的所有测序费用将由 慈善捐赠给我们医院，并没有预算的赠款。我们将尽一切努力 每年通过机器学习和信息学使用MARRVEL诊断剩余的60人 平台，候选基因的果蝇功能研究，并通过持续6个月，12个月和2年 对患者进行随访，我们将使用GeneMatcher和Matchmaker等配对工作 交换以及我们自己的基因组数据库从UDN和其他研究来一个遗传 诊断.所有受试者将接受来自训练有素的团队的遗传咨询，并将为我们提供宝贵的 医学、心理和社会数据，以指导如何在服务不足的人群中实施基因组学 影响护理和家庭。这项工作不仅将产生新的见解，罕见的 疾病，未确诊家庭的诊断和基因组学的扩大作用，它将指导我们在未来 提供基因组学和功能研究，为所有个人服务，无论其支付能力如何。

PROJECT SUMMARY Here we propose to advance the goal of NHGRI to implement genomic medicine and focus on individuals who have not been able to afford DNA testing. The research takes place in the Department of Molecular and Human Genetics at Baylor College of Medicine (BCM) and Texas Childrens Hospital (TCH). Our team of clinicians, geneticists, computer scientists, genomicists and model organism researchers has had a five-year term of success with the Undiagnosed Diseases Network (UDN) Model Organisms Screening Center (MOSC). This has included successfully identifying a number of new disease genes such as EBF3, IRF2BPL, NACC1, TBX2, TOMM70, CDK19, ACOX1, WDR37, and ATP5F1D. We propose to recruit 100 individuals from an underserved population in Houston, Texas with suspected rare disease and without the means to pay for DNA sequencing through insurance. We will provide whole-exome sequencing which will generate a CAP/CLIA report that we anticipate could diagnose 35-40 individuals per year. The remaining individuals will then be converted to a family-based trio exome design. All the sequencing costs of this project will be covered by philanthrophic donation to our hospital and are not budgeted to the grant. We will make every effort to diagnose the remaining 60 individuals per year through machine learning and informatics using the MARRVEL platform, Drosophila functional studies of candidate genes and through ongoing 6 month, 12 month and 2 year follow-up with the patients where we will use matchmaking efforts such as GeneMatcher and Matchmaker exchange as well as our own genomic databases from the UDN and other studies to come to a genetic diagnosis. All subjects will receive genetic counseling from a trained team and will provide us with valuable medical, psychological and social data to guide how genomic implementation in an underserved population is perceived, impacts care and impacts the family. This work will not only produce novel insights into rare disease, diagnosis for undiagnosed families and an expanded role for genomics, it will guide us in the future to provide genomics and functional research to serve all individuals regardless of their ability to pay.