Characterizing Genetic Risk Through Next Generation Sequencing in the Dover Amish (Pilot Year 6)
Matthew Demczko, Nemours (PI); Erin Crowgey, Nemours(Co-I); Michael Fox, Nemours(Co-I); Anders Kolb, Nemours(Co-I); Erik Puffenberger, Nemours(Co-I); Kevin Strauss, Nemours(Co-I)
What we wanted to learn and why it matters
Next generation sequencing (NGS) technology has transformed the practice of clinical genetics and patient care. This powerful technology has not yet been used to identify patients who are risk for genetic disorders but are not symptomatic. The Old Order Amish (Plain community) are an especially vulnerable population who have a significant risk for debilitating and oftentimes fatal inherited disorders. In this study, we aimed to better understand the genetic risk factors within the Dover Plain community that would permit earlier diagnosis and personalized care delivery.. We also assessed the community’s perception of broad genetic screening and perspectives on how the data should be shared and used.
What we did and learned
We used two unique NGS approaches to determine the rates of disease-causing genes present in samples from 211 individuals. Of the panel data processed thus far, we have identified 145 unique variants present within the community. These variants are associated with over 50 disorders (metabolic, endocrine, cardiovascular most commonly), many with available treatment and/or screening modalities available. Our survey indicated that the community is well versed in genetic testing and screening and welcomes this type of work to improve the health of future generations. Over 80% said that this type of screening would help to avoid surprises at birth or during a child’s early life. Almost all (90%) said that it would be helpful for extended family members to be aware of the genetic conditions they may be at risk for and 83% expressed a desire to know their status for conditions that begin in adulthood so they might seek treatment.
To read more about this study
Williams, K. B., Brigatti K. W., Puffenberger E. G., Gonzaga-Jauregui C., Griffin L. B., Martinez E. D., et al. (2019). Homozygosity for a mutation affecting the catalytic domain of tyrosyl-tRNA synthetase (YARS) causes multisystem disease.. Hum Mol Genet. 28(4), 525-538. [PMCID: PMC6360277]
Demczko MM. A Wave. JAMA. 2019;322(9):815–816. doi:10.1001/jama.2019.12599