UW Undiagnosed Genetic Diseases Program
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 1,000
- 试验地点
- 2
- 主要终点
- Number of New Disease Genes Discovered
研究概览
简要总结
The primary purpose of this study is to discover new disease genes for rare Mendelian disorders and its secondary purpose include diagnosing people with rare genetic disorders that have not been previously diagnosed through conventional clinical means, learning more about the pathobiology of genetic disorders, and developing novel diagnostic technologies and analytics. 500 participants with undiagnosed and suspected genetic disorders will be recruited.
详细描述
An estimated 10,000 rare Mendelian genetic disorders affect, in aggregate, one in twelve individuals. Importantly, just over half of these diseases have a known genetic cause. This leaves thousands of disease genes waiting to be discovered and millions of affected individuals without a diagnosis. The investigators will address these critical issues in genomic medicine by using genome sequencing and other 'omics technologies to assess patients whose comprehensive clinical workups have failed to yield a diagnosis. The hypothesis is that, when carefully selected, these undiagnosed disease patients will be a rich resource for new disease gene discovery.
This study is the research arm of the UW Undiagnosed Disease program (UW-UDP). The primary objective of this study is to discover new disease genes and expand the known phenotypes of rare Mendelian disorders. The secondary objectives are: a) Diagnose individuals with genetic disorders who have not been diagnosed using conventional clinical means and provide them with actionable knowledge to manage their disorders; b) Improve our understanding of the pathobiology of genetic disorders and the relationships between genomic variation and disease; and c) Develop and trial novel diagnostic technologies and analytics.
These objectives will be achieved through three aims:
Aim 1: Identify candidate disease variants in individuals suspected of an undiagnosed genetic disorder through the use of trio short read genome sequencing and data sharing with the rare disease databases GeneMatcher and MatchMaker Exchange.
Aim2: Further evaluate those individuals not diagnosed in Aim 1 by using novel 'omics technologies and bioinformatics algorithms. These approaches include a) ultra-long read de novo assembly-based genomic sequencing; b) RNA-Seq; c) epigenomics profiling, and d) conformational analysis of chromatin organization.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- — 至 100 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The applicant has a condition that remains undiagnosed despite thorough evaluation by healthcare providers (including clinical genetic testing).
- •The applicant has at least one objective finding that is likely to have an identifiable genetic etiology.
- •The applicant likely has a currently undescribed/new genetic condition or a known genetic condition associated with a novel gene.
- •The applicant/legal guardian agrees to the collection, storage and recurrent sharing of coded information and biomaterials for research and diagnostic purposes both within and outside of the University of Wisconsin-Undiagnosed Diseases Program (UW-UDP)
- •The applicant/legal guardian agrees to receive secondary findings from genetic testing.
- •The applicant/legal guardian has sufficient proficiency in English to understand the consent.
排除标准
- •The applicant already has a diagnosis that explains the objective findings.
- •A specific diagnosis is suspected and a standard clinical workup performed by the referring/primary care provider would be appropriate.
- •The UW-UDP is unlikely to improve on the comprehensive workup the applicant has already received.
- •The applicant's symptoms are likely multifactorial or due to a non-genetic cause.
结局指标
主要结局
Number of New Disease Genes Discovered
时间窗: up to 5 years
Number of Expanded Disease Gene Phenotypes
时间窗: up to 5 years
次要结局
- Number of Participants Diagnosed per Analytical Technique(up to 5 years)
- Number of Participants who are Diagnosed in 5 years(up to 5 years)
- Diagnostic Rate by Disease Presentation(up to 5 years)