April 16, 2013
Amish Lend Window into Research of Rare Genetic Disease
Dr. Matthew Pelletier, department of biology chair and associate professor of biology at Houghton College, has been conducting research, in conjunction with a select group of Houghton students, on propionic acidemia (PA), a rare genetic disease prevalent in the local New York / Pennsylvania Amish populations.
PA is inherited by only one in 100,000 of the country’s population. It is a biochemical defect that prevents those in whom it is present from adequately metabolizing certain amino acids. Lethargy, ketosis, developmental retardation, episodic vomiting, and protein intolerance are characteristic of PA. Those diagnosed with PA are treated with a low-protein diet and other dietary alterations, meaning diseased individuals may lead relatively healthy lives. Early diagnosis is paramount, as there was, until 10 years ago, no routine screening for PA in New York and Pennsylvania. If a carrier generally consumed a low-protein diet or had mild symptoms, the disease may have gone undiagnosed.
Pelletier gave a talk on DNA typing for Houghton alumni during the 2011 homecoming weekend. After his talk Pelletier was approached by an alumnus regarding the child of an Amish friend with PA and suggested Pelletier might be interested in researching the disease further, in hopes of contributing to development in current and future PA treatment.
The team met and researched with Dr. Holmes Morton, a Lancaster County physician and Harvard Medical School graduate recognized for working in depth with the area’s Amish and Mennonite populations. Pelletier also had the opportunity to meet and learn about the Amish community family with the PA-carrying child. In a community of 500 the family asserted the known existence of seven diagnosed cases of PA.
The Amish family with whom Pelletier discussed the community’s known PA ratio arranged for Houghton students Stephen Trinidad, Ashley Page-Trinidad, Kara Mastin, Shannon Hritz, and Jonathan Figueroa to meet the community, present a summary of the disease – “kind of like Genetics 101 for PA,” says Pelletier – and offer testing. Dozens of volunteers had their cheeks swabbed for DNA samples after giving informed consent.
“One of the biggest challenges in the research is getting the family pedigrees right. Early on in our screening experiment, some of the data we had gathered didn’t make sense -- a child was a carrier for the disease-causing allele, while neither parent was, “ reports Pelletier. “It turns out there were three different volunteers with the same first and last name --a senior, junior, and 3rd --and I had gotten them mixed up.” Pelletier was thankful for the Amish family’s cooperation -- “With their help, I was able to straighten that out.”
Back at Houghton, the team conducted DNA sequencing to check for individuals carrying the disease without their knowledge and for carriers with the disease-causing allele. The team pinpointed several carriers from the volunteer community sample. After further research and collaboration with Morrow, it was discovered that several patients with PA developed severe heart problems, which may be related to the variable regions known as “SNPs,” or single nucleotide polymorphisms present in certain individuals with PA.
“Ultimately, this could help us understand the pathophysiology of the disease and how to best treat it” reports Pelletier. Soon Pelletier’s Human Genetics and Disease class students will examine the SNPs from the Amish community. “We hypothesize that the variability among patients with regard to heart problems might be related to some of these SNPs present among different individuals,” Pelletier says.
The team’s research was recently presented by Pelletier at a national conference on PA, “The next steps will involve more of a focus on treatment of the disease,” assures Pelletier.
In addition to scientific research, Pelletier valued his experience of an often misunderstood American culture and appreciated the opportunity to meet Amish community members. “I feel like I’ve made some friends in the community,” says Pelletier, “and it is extremely rewarding to be working on a problem that could one day really make a difference in the lives of people living with this disease.”