Genomic medicine and gene function implementation for an underserved population

针对服务不足人群的基因组医学和基因功能实施

• 批准号: 10640103
• 负责人: HUGO J BELLEN
• 金额: $ 96.22万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-13 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10640103
• 关键词: Affect; American; Artificial Intelligence; Attitude; Bioinformatics; Biological Assay; Candidate Disease Gene; Caring; Child; Clinic; Clinical; Computers; DNA; DNA sequencing; Data; Databases; Diagnosis; Disease; Drosophila genus; Drosophila melanogaster; Enrollment; Expert Systems; Explosion; Family; Future; Genes; Genetic Counseling; Genetic Diseases; Genetic Research; Genetic Variation; Genetic study; Genome; Genomic medicine; Genomics; Goals; Grant; Health Insurance; Healthcare; Hospitals; Human; Human Genetics; Individual; Informatics; Insurance; Insurance Coverage; Learning; Machine Learning; Medical; Medical Genetics; Medicine; Minority Groups; Modeling; Molecular Genetics; National Human Genome Research Institute; Parents; Patient-Focused Outcomes; Patients; Pediatric Hospitals; Perception; Persons; Play; Population; Rare Diseases; Recommendation; Reporting; Research; Research Personnel; Role; Scientist; Societies; Technology; Testing; Texas; Time; Training; Underserved Population; Validation; Variant; Work; actionable mutation; bioinformatics tool; cohort; college; cost; design; diagnostic tool; ethnic minority; exome; exome sequencing; experience; follow-up; gene discovery; gene function; genetic disorder diagnosis; genomic data; innovation; insight; interest; low socioeconomic status; medical schools; model organism; network models; novel; operation; personalized genomics; personalized medicine; proband; programs; protein function; psychologic; public health insurance; recruit; research clinical testing; research study; screening; social; success; tool; virtual visit

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.

项目概要 在此我们建议推进NHGRI实施基因组医学并关注个体的目标 那些无力承担 DNA 检测费用的人。该研究在分子和科学系进行 贝勒医学院 (BCM) 和德克萨斯儿童医院 (TCH) 的人类遗传学。我们的团队 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经历了五年 未确诊疾病网络 (UDN) 模式生物筛查中心 (MOSC) 的成功期限。 这包括成功鉴定许多新的疾病基因，如 EBF3、IRF2BPL、NACC1、 TBX2、TOMM70、CDK19、ACOX1、WDR37 和 ATP5F1D。我们拟从以下单位招聘 100 名人员： 德克萨斯州休斯顿的医疗服务不足的人群患有疑似罕见病且无力支付医疗费用 通过保险进行 DNA 测序。我们将提供全外显子组测序，生成 CAP/CLIA 报告称，我们预计每年可以诊断 35-40 人。剩下的人将被 转换为基于家族的三外显子组设计。该项目的所有测序费用将由 对我们医院的慈善捐赠并未列入补助金预算。我们将竭尽全力 每年使用 MARRVEL 通过机器学习和信息学诊断剩余的 60 个人 平台，对候选基因进行果蝇功能研究，并持续进行 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 UDN 基因组数据库和其他研究，以得出遗传 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信息 医学、心理和社会数据指导如何在服务不足的人群中实施基因组 被感知，影响护理并影响家庭。这项工作不仅会对稀有的事物产生新颖的见解 疾病、未确诊家庭的诊断以及基因组学的扩大作用，它将指导我们的未来 提供基因组学和功能研究，为所有人服务，无论其支付能力如何。

项目成果

Lessons learned from additional research analyses of unsolved clinical exome cases.

• DOI: 10.1186/s13073-017-0412-6
• 发表时间: 2017-03-21
• 期刊: Genome medicine
• 影响因子: 12.3
• 作者: Eldomery MK;Coban-Akdemir Z;Harel T;Rosenfeld JA;Gambin T;Stray-Pedersen A;Küry S;Mercier S;Lessel D;Denecke J;Wiszniewski W;Penney S;Liu P;Bi W;Lalani SR;Schaaf CP;Wangler MF;Bacino CA;Lewis RA;Potocki L;Graham BH;Belmont JW;Scaglia F;Orange JS;Jhangiani SN;Chiang T;Doddapaneni H;Hu J;Muzny DM;Xia F;Beaudet AL;Boerwinkle E;Eng CM;Plon SE;Sutton VR;Gibbs RA;Posey JE;Yang Y;Lupski JR
• 通讯作者: Lupski JR

Precision therapy for a medically actionable ATP1A3 variant from a genomic medicine program in an underserved population.

• DOI: 10.1002/mgg3.2272
• 发表时间: 2023-12
• 期刊: Molecular genetics & genomic medicine
• 影响因子: 2

Antioxidant proteins TSA and PAG interact synergistically with Presenilin to modulate Notch signaling in Drosophila.

• DOI: 10.1007/s13238-011-1073-7
• 发表时间: 2011-07
• 期刊: Protein & cell
• 影响因子: 21.1
• 作者: Wangler MF;Reiter LT;Zimm G;Trimble-Morgan J;Wu J;Bier E
• 通讯作者: Bier E

Unusually early presentation of small-bowel adenocarcinoma in a patient with Peutz-Jeghers syndrome.

黑斑息肉综合征患者异常早期出现小肠腺癌。

• DOI: 10.1097/mph.0b013e318282db11
• 发表时间: 2013
• 期刊: Journal of pediatric hematology/oncology
• 作者: Wangler,MichaelF;Chavan,Rishikesh;Hicks,MJohn;Nuchtern,JedG;Hegde,Madhuri;Plon,SharonE;Thompson,PatrickA
• 通讯作者: Thompson,PatrickA

Retrospective Diagnosis of Ataxia-Telangiectasia in an Adolescent Patient With a Remote History of T-Cell Leukemia.

具有 T 细胞白血病远史的青少年患者共济失调毛细血管扩张症的回顾性诊断。

• DOI: 10.1097/mph.0000000000001672
• 发表时间: 2021
• 期刊: Journal of pediatric hematology/oncology
• 作者: Sze,Sei-GyungK;Lederman,HowardM;Crawford,ThomasO;Wangler,MichaelF;Lewis,AndreaM;Kastan,MichaelB;Dibra,HarpreetK;Taylor,AlexanderMR;Wechsler,DanielS
• 通讯作者: Wechsler,DanielS