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

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.

Inclusion Criteria:

- Any person of Amish or Mennonite descent

Exclusion Criteria:

- Individuals who are not of Amish or Mennonite descent