A collaboration between researchers at UTHealth School of Dentistry at Houston and Baylor College of Medicine has led to a study published in the journal Science. “Allele-Specific Epigenome Maps Reveal Sequence-Dependent Stochastic Switching at Regulatory Loci” appeared in the journal’s Aug. 23 online edition.
UTHealth Assistant Professor Walid Fakhouri, MSc, PhD and Research Assistant Jessica Bertol, PhD, were among collaborators working with the principal investigator, Dr. Aleks Milosavljevic of BCM, to advance understanding of how variations in regulatory DNA regions and human genome signatures affect gene expression. It is an area of research that remains a challenge for biomedical and clinical applications.
The Human Genome Project revealed that each human cell has approximately 20,000 genes, with each gene distinctly regulated by time and position to determine the cell’s fate. Genes are regulated by codes encrypted in the DNA sequence and by the epigenetic process, which transforms undifferentiated cells into cells that give rise to organs and tissues the originals did not have. Variations in regulatory DNA sequences and marks can disrupt gene expression and alter the way cells develop.
The new study showed that genes inherited from the mother have different “signatures” in their DNA regulatory codes than corresponding genes inherited from the father, and that those differences are associated with DNA sequence variations that affect gene expression. Fakhouri’s lab contributed to the study by revealing how the differences can work at the molecular level.
In a BCM news release, Milosavljevic said the study's findings could be useful in a variety of ways.
“For instance, our findings may add another layer of complexity that so far has not been taken into account in certain intricate human diseases,” he said. “If we add this layer of complexity, we might be able to better understand how dosage-sensitive genes may contribute to human diseases that have so far been hard to tackle, such as neuropsychiatric disorders.
“This work is meant to provide insights into a new important layer of biological complexity,” he added, “and hopefully create the basis for subsequent research into specific diseases.”