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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02927158
Recruitment Status : Recruiting
First Posted : October 6, 2016
Last Update Posted : January 10, 2018
Horizon Pharma USA, Inc.
Information provided by (Responsible Party):
Lina Ghaloul Gonzalez, University of Pittsburgh

September 22, 2016
October 6, 2016
January 10, 2018
August 2016
August 2026   (Final data collection date for primary outcome measure)
Exome and genome sequencing results for clinical diagnosis in participants. [ Time Frame: 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
Same as current
Complete list of historical versions of study NCT02927158 on Archive Site
Exome and genome sequence results for population genetic studies [ Time Frame: 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.
Same as current
Not Provided
Not Provided
Exome and Genome Analysis to Elucidate Genetic Etiologies and Population Characteristics in the Plain Community
Use of Whole Exome Sequencing/Whole Genome Sequencing in the Plain Communities
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.
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.
Observational Model: Cohort
Time Perspective: Prospective
Not Provided
Retention:   Samples With DNA
Whole blood will be collected and DNA will be isolated and stored. Samples may also be collected on newborn screening filter papers.
Non-Probability Sample
Families of Amish/Mennonite background which include at least one individual with a clinical phenotype and a pedigree suggestive of genetic disease will be considered for the undiagnosed disease portion of the study. Initial outreach will be to Plain Communities in western Pennsylvania, but all Pain Community members are eligible as long as they have been evaluated by a local clinical geneticist. Any individual (and their family members) from the Plain Community is eligible for the population based studies of founder effects and genetic drift.
Undiagnosed Disease
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
August 2030
August 2026   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Any person of Amish or Mennonite descent

Exclusion Criteria:

  • Individuals who are not of Amish or Mennonite descent
Sexes Eligible for Study: All
up to 100 Years   (Child, Adult, Older Adult)
Contact: Cate Walsh Vockley, MS, LCGC 412-692-7349
Contact: Jenifer Baker, MA 412-6926378
United States
Not Provided
Plan to Share IPD: Yes
Plan Description: Results relevant to the participant's clinical condition will be verified in a CLIA-certified laboratory and reported to the participant.
Lina Ghaloul Gonzalez, University of Pittsburgh
University of Pittsburgh
Horizon Pharma USA, Inc.
Principal Investigator: Lina Ghaloul Gonzalez, MD University of Pittsburgh
University of Pittsburgh
January 2018