Genomic medicine and gene function implementation for an underserved population

项目总结 在这里，我们建议将NHGRI的目标推进到实施基因组医学并专注于个体 那些负担不起DNA检测的人。这项研究在分子和生物系进行。 贝勒医学院(BCM)和德克萨斯儿童医院(TCH)的人类遗传学研究。我们的团队 临床医生、遗传学家、计算机科学家、基因学家和模型生物体研究人员已经有了五年的 未诊断疾病网络(UDN)模式生物筛选中心(MOSC)的成功期限。 这包括成功地鉴定了一系列新的疾病基因，如EBF3、IRF2BPL、NACC1、 TBX2、TOMM70、CDK19、ACOX1、WDR37和ATP5F1D。我们建议从一个 得克萨斯州休斯敦服务不足的人群患有疑似罕见疾病，没有能力支付 通过保险进行DNA测序。我们将提供完整的外显子组测序，这将产生CAP/CLIA 我们预计每年可以诊断35-40个人的报告。剩下的人将被 转换为基于家族的三重外显体设计。该项目的所有排序费用将由 慈善捐赠给我们的医院，并不是预算中的赠款。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个人 平台，果蝇候选基因的功能研究，并通过正在进行的6个月、12个月和2年 对我们将使用GeneMatcher和MatchMaker等相亲努力的患者进行随访 交换以及我们自己的基因组数据库从UDN和其他研究中得出了一个基因 诊断。所有受试者都将接受训练有素的团队的遗传咨询，并将为我们提供有价值的 医疗、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 被察觉，影响照顾，影响家庭。这项工作不仅将产生对稀有 疾病，对未确诊家庭的诊断，以及基因组学的扩大作用，它将指导我们未来 提供基因组学和功能研究，为所有个人服务，无论他们的支付能力如何。

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.