Researchers at North Carolina State University have created an innovative array to analyze the methylation levels of genes found in imprint control regions (ICRs) in the human genome. This array offers a budget-friendly and effective way to investigate possible associations between environmental factors and epigenetic disruptions linked to early developmental origins of diseases and behavioral issues.
Researchers at North Carolina State University have developed an innovative array to analyze the methylation levels of genes found in imprint control regions (ICRs) in the human genome. This array offers a budget-friendly and effective way to investigate possible associations between environmental factors and epigenetic disruptions linked to early developmental origins of diseases and behavioral issues.
ICRs manage the expression of imprinted genes—those genes for which only one parent’s version is active, while the other is silenced during initial development. These imprinted genes are particularly significant for epidemiologists, geneticists, and toxicologists studying the links between environmental factors and disease, as the methylation patterns that regulate their expression can be influenced by the environment.
Such DNA methylation changes can remain stable throughout an individual’s life and may even be inherited by their descendants. This area is crucial in epigenetics, which examines heritable shifts in gene expression that occur without alterations to the DNA sequence.
“Methylation—determining whether a gene is ‘on’ or ‘off’—is the most straightforward aspect to investigate when exploring epigenetic influences,” explains Cathrine Hoyo, a professor of biological sciences at NC State and one of the lead authors of the study. “It provides a starting point for understanding the connections between the environment and gene expression.”
While various methylation arrays are available for studying gene expression, most do not focus on ICR-specific probes. As a result, scientists examining imprinted gene regulation typically need to sequence an entire genome, a process that is expensive, time-consuming, and inefficient for large population analyses.
This new array features 22,000 fluorescent probes tailored to 1,000 of the 1,488 known ICRs within the human genome. These probes are short DNA sequences aimed at specific methylation sites within the ICRs, with different probes binding to either the methylated or unmethylated forms. Each type of probe emits a distinct fluorescent signal, enabling the measurement of the binding ratio and allowing determination of the methylation level at each location.
As a proof of concept, the research team analyzed DNA from a group of Alzheimer’s patients, comparing the ICR methylation data from the array with results from whole genome sequencing, and found a strong correlation between both methods. Notably, the array results were ready within a week, contrasting sharply with the months typically needed for whole genome interpretations.
“In extensive studies, we must screen the participants,” Hoyo points out. “For instance, with 1,000 participants, conducting complete genomic sequences in a timely and cost-efficient manner isn’t feasible. It’s particularly inefficient when we are focused solely on 22,000 specific sites among millions in the genome.
“This array efficiently conducts screening for us—it targets only the relevant sites and allows us to dedicate time and resources to full sequencing only when it’s absolutely necessary. Essentially, it helps us filter out the unnecessary data so we can concentrate on the ICRs that might be critical in disease development.”
This research is published in Epigenetics Communications and received support from the National Institutes of Health through grant numbers R01ES093351, R01HD098857, R01MD011746, and R21HD093351, along with assistance from NC State’s Center for Human Health and the Environment. The technology is now licensed by TruDiagnostic, Inc., with Ryan Smith from TruDiagnostic serving as a co-corresponding author. Other contributors include lead author Natalia Carreras-Gallo, Varun B. Dwaraka, and Tavis L. Mendez from TruDiagnostic; Dereje D. Jima, David A. Skaar, Antonio Planchart, and Randy L. Jirtle from NC State University; and Wanding Zhou from the University of Pennsylvania.
