Exome and Genome Analysis to Elucidate Genetic Etiologies and Population Characteristics in the Plain Community

Recruiting

• Conditions: Undiagnosed Disease

• Registration Number: NCT02927158
• Lead Sponsor: University of Pittsburgh

Brief Summary

This study is designed to utilize whole exome and whole genome sequencing techniques to identify underlying genetic causes for undiagnosed disorders in the Plain Communities, and to do population genetic studies looking at genetic drift and founder mutations in this unique population.

Detailed Description

The long term goal of this proposal is to establish a Translational Medicine Program for the Old Order Amish and Mennonite communities that is accessible to their members with decreasing cost and effective diagnostic strategies, and to leverage the genetic information obtained to better understand the genetic forces and risks driving the health of these populations. As a bridge to do so, next-generation sequencing technology will be used to identify genetic defects in Old Order Amish families/individuals who have a clinical picture suggestive of a Mendelian disorder but with unknown diagnosis. Investigators plan to develop targeted analytical NGS panels optimized for general use in the clinical setting when dealing with Plain Communities patients and families, yielding better and more prompt clinical intervention and improvement of outcomes. The study also involves use of whole genome sequencing for a mutant allele discovery platform to identify novel genetic risks in this population not yet identified in patients, and to use this platform to describe genetic differences in Old Order Amish communities across Pennsylvania and ultimately across the country. With WGS will be used to analyze population genetics by comparing the distribution of genetic variants among the various Amish communities and to compare these with their European ancestry variants available in 1000 genome project, to study the influence of founder-selection and genetic drift in these populations.

Study Timeline

• Study Start: 2016-08
• Study First Submitted: 2016-09-22
• Study First Submitted QC: 2016-10-05
• Study First Posted: 2016-10-06
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-28
• Last Update Posted: 2025-05-01
• Primary Completion: 2026-08
• Study Completion: 2030-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Any person of Amish or Mennonite descent

Exclusion Criteria

• Individuals who are not of Amish or Mennonite descent

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Exome and genome sequencing results for clinical diagnosis in participants.	Within approximately one year for each participant	Each participant will be sequenced and DNA data will be analyzed for gene mutations consistent with the clinical symptomatology

Secondary Outcome Measures

Name	Time	Method
Exome and genome sequence results for population genetic studies	Through study completion, approximately 5 years	Exome and genome sequencing will be used to evaluate genetic changes in specific communities within the Amish and Mennonite communities. These changes/differences will be compared among the groups to show how population migration and new genetic mutations effect the burden of genetic disease in these populations.

Trial Locations

Locations (1)

Children's Hospital of Pittsburgh of UPMC; 🇺🇸 Pittsburgh, Pennsylvania, United States