Since the mid-1900s, researchers have studied Finland’s uniquely high frequency and geographic distribution of cleft palate birth defects. The cause was long presumed to be genetic.
Now, researchers at Michigan State University (MSU) and their collaborators have identified a likely culprit: a change in a DNA variant near the IRF6 gene. This DNA change, which affects the risk of cleft palate but not cleft lip, is found only in Finland and Estonia.
The study, published in Nature Communications, compared genetic data from Finland to the “next largest” population of people with Finnish ancestry, which is in Michigan’s Upper Peninsula. Researchers noted that while the DNA change is present in Michigan, the region does not share Finland’s high rate of cleft palate cases.
Other factors behind cleft palate
This difference has led scientists to explore alternative explanations.
“If we find the DNA change in those Michigan samples, but the frequency of cleft palate is not high like it is in Finland, that would suggest an environmental or other component that makes cleft palate less common in Michigan than in Finland, despite the genetic connection between the people,” said Brian Schutte, geneticist, associate professor and co-director of the D.O.-Ph.D. Physician-Scientist Training Program at MSU’s College of Osteopathic Medicine.
Next phase of research
In the next phase of research, Schutte will work with the Michigan Department of Health and Human Services to genotype blood samples from Michigan’s BioTrust. These samples will come from babies born with cleft palates in five counties with significant populations of Finnish ancestry: Ontonagon, Houghton, Schoolcraft, Marquette and Chippewa.
“This has clinical, risk and public health ramifications,” Schutte added.
MSU researchers collaborated with teams from FinnGen, AbbVie Inc., the University of Helsinki, the University of Washington School of Dentistry, the Estonian Genome Center and others. They tied the DNA change, which alters a conserved binding site for the transcription factor IRF6, to Finland’s statistically significant geographic distribution of cleft palate cases. The prevalence of cleft palate increases from the southwest to the northeast of Finland, a pattern not observed anywhere else in the world.
By studying samples from Michigan, researchers hope to further investigate how demographic or environmental factors may influence cleft palate prevalence, shedding light on how genetics and environment interact in this rare condition.
