Clinical trial NCT02927158: Exome and Genome Analysis to Elucidate Genetic Etiologies and Population Characteristics in the Plain Community
Official title: Use of Whole Exome Sequencing/Whole Genome Sequencing in the Plain Communities
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Undiagnosed Disease
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Horizon Pharma USA, Inc.
First posted: 2016-10-06
Enrollment: 300
Sex: ALL
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 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.

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.

Eligibility criteria: Inclusion Criteria:

* Any person of Amish or Mennonite descent

Exclusion Criteria:

* Individuals who are not of Amish or Mennonite descent

Primary outcomes:
measure: Exome and genome sequencing results for clinical diagnosis in participants.
timeFrame: Within approximately one year for each participant
Secondary outcomes:
measure: Exome and genome sequence results for population genetic studies
timeFrame: Through study completion, approximately 5 years
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh of UPMC
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Lina Ghaloul Gonzalez, MD
role: PRINCIPAL_INVESTIGATOR
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