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| Name | Class |
|---|---|
| Horizon Pharma USA, Inc. | INDUSTRY |
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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.
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.
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| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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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.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Cate Walsh Vockley, MS, LCGC | Contact | 412-692-7349 | catherine.walshvockley@chp.edu | |
| Jenifer Baker, MA | Contact | 412-6926378 | jennifer.baker@chp.edu |
| Name | Affiliation | Role |
|---|---|---|
| Lina Ghaloul Gonzalez, MD | University of Pittsburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital of Pittsburgh of UPMC | Recruiting | Pittsburgh | Pennsylvania | 15224 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 15496913 | Background | International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature. 2004 Oct 21;431(7011):931-45. doi: 10.1038/nature03001. | |
| 19498102 | Background | Pruitt KD, Harrow J, Harte RA, Wallin C, Diekhans M, Maglott DR, Searle S, Farrell CM, Loveland JE, Ruef BJ, Hart E, Suner MM, Landrum MJ, Aken B, Ayling S, Baertsch R, Fernandez-Banet J, Cherry JL, Curwen V, Dicuccio M, Kellis M, Lee J, Lin MF, Schuster M, Shkeda A, Amid C, Brown G, Dukhanina O, Frankish A, Hart J, Maidak BL, Mudge J, Murphy MR, Murphy T, Rajan J, Rajput B, Riddick LD, Snow C, Steward C, Webb D, Weber JA, Wilming L, Wu W, Birney E, Haussler D, Hubbard T, Ostell J, Durbin R, Lipman D. The consensus coding sequence (CCDS) project: Identifying a common protein-coding gene set for the human and mouse genomes. Genome Res. 2009 Jul;19(7):1316-23. doi: 10.1101/gr.080531.108. Epub 2009 Jun 4. |
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Results relevant to the participant's clinical condition will be verified in a CLIA-certified laboratory and reported to the participant.
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| ID | Term |
|---|---|
| D000080842 | Undiagnosed Diseases |
| ID | Term |
|---|---|
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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Whole blood will be collected and DNA will be isolated and stored. Samples may also be collected on newborn screening filter papers.
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| 21331778 | Background | Ku CS, Naidoo N, Pawitan Y. Revisiting Mendelian disorders through exome sequencing. Hum Genet. 2011 Apr;129(4):351-70. doi: 10.1007/s00439-011-0964-2. Epub 2011 Feb 18. |
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