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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Use of Whole Exome Sequencing/Whole Genome Sequencing in the Plain Communities

Conditions
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Undiagnosed Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any person of Amish or Mennonite descent Exclusion Criteria: Individuals who are not of Amish or Mennonite descent

Ages Eligible for Study
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Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exome and genome sequencing results for clinical diagnosis in participants. | Each participant will be sequenced and DNA data will be analyzed for gene mutations consistent with the clinical symptomatology | Within approximately one year for each participant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exome and genome sequence results for population genetic studies | 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. | Through study completion, approximately 5 years |