Ignite Creation Date:
2024-05-06 @ 3:18 PM
Last Modification Date:
2024-10-26 @ 1:46 PM
Study NCT ID:
NCT04586075
Status:
RECRUITING
Last Update Posted:
2023-10-19
First Post:
2020-10-06
Brief Title:
UW Undiagnosed Genetic Diseases Program
Sponsor:
University of Wisconsin Madison
Organization:
University of Wisconsin Madison
Study Overview
Official Title:
UW Undiagnosed Genetic Diseases Program
Status:
RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 over approximately 5 years time
Detailed Description:
An estimated 10000 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
Aim 3 Provide functional assessments of selected candidate disease genes and genomic variants discovered in Aims 1 and 2 through collaborations with UW and external model organism researchers These efforts will be facilitated through the use of a UW model organism researcher database that is linked to the Canadian Rare Diseases Models and Mechanisms Network database and an emerging global network of model organism researcher databases
This research project is closely integrated with the UW-UDPs comprehensive clinical evaluations of undiagnosed patients The standard clinical care component entails patient referral collection and pre-visit assessment of medical records and clinic visits for extensive phenotyping at the beginning of the study and for the return of results at the end of the study The research workflow includes genome sequencing data sharing with global disease gene discovery networks and follow-up studies to determine causality of variants identified by genetic testing This study will advance understanding of the pathobiology of genetic disease improve clinical diagnostics and aid in the diagnosis and management of individuals with previously undiagnosed rare disorders both within Wisconsin and beyond its borders
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
Aim 3 Provide functional assessments of selected candidate disease genes and genomic variants discovered in Aims 1 and 2 through collaborations with UW and external model organism researchers These efforts will be facilitated through the use of a UW model organism researcher database that is linked to the Canadian Rare Diseases Models and Mechanisms Network database and an emerging global network of model organism researcher databases
This research project is closely integrated with the UW-UDPs comprehensive clinical evaluations of undiagnosed patients The standard clinical care component entails patient referral collection and pre-visit assessment of medical records and clinic visits for extensive phenotyping at the beginning of the study and for the return of results at the end of the study The research workflow includes genome sequencing data sharing with global disease gene discovery networks and follow-up studies to determine causality of variants identified by genetic testing This study will advance understanding of the pathobiology of genetic disease improve clinical diagnostics and aid in the diagnosis and management of individuals with previously undiagnosed rare disorders both within Wisconsin and beyond its borders
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| SMPH | OTHER | None | None |
| Protocol Version 8202020 | OTHER | UW Madison | None |