Health

How does DNA Atlas provide clues to heart disease risk?


“This new atlas will help us narrow down the cell types responsible for gene regulation in the cardiovascular system. It will also provide a pathway to explain non-coding disease variants in the right tissues. best,” said Miller, UVA Center for Public Health Genomics and Department of Biochemistry and Molecular Genetics and Public Health Sciences. “Knowing how these variants function through cell type-specific regulatory factors will help facilitate translational and mechanistic studies across the coronary disease spectrum.”

As plaque builds up, the arteries narrow. This reduces the supply of oxygen-rich blood to major organs in the body, which can lead to a heart attack or death.

Both environmental and genetic factors contribute to an individual’s lifetime risk of developing coronary heart disease. Understanding which genes may play a part in driving the risk of disease in its early stages could help researchers develop more precise or preventive treatments.

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“Using state-of-the-art single-cell sequencing technology, we have increased the resolution of this atlas to an unprecedented level,” said co-author Chongzhi Zang, PhD, also a member of China UVA’s Center for Public Health Genomics said Department of Biochemistry and Molecular Genetics and Public Health Sciences. “For the first time, we were able to directly study the chromatin factors that control coronary artery disease genes in thousands of individual cell nuclei.”

Chromosomes are the combination of DNA and proteins that make up our chromosomes; it plays an important role in directing the activity of genes. In this case, the new chromosome atlas will allow researchers to better understand how chromatin controls genes that contribute to coronary disease.

“By pinpointing genes that can cause disease, we can ultimately develop more effective interventions tailored to an individual’s risk profile,” Miller said. “Our work aims to advance our ability to target genes in specific cells or cell types.”

Using coronary artery segments from 41 patients with different stages of coronary heart disease, Miller and colleagues profiled more than 28,000 nuclei and identified 14 distinct clusters representing different cell types such as smooth muscle cells, endothelial cells, and immune cells. Additional analyzes discovered more than 320,000 regulatory and transcription factors at the cellular level, which regulate the switching on or off of RNA molecules to make proteins or serve other functions.

Using this approach, Miller and colleagues were able to capture the regulatory structure of several important genes, including PRDM16 and TBX2. These genes are transcriptional regulators that have been implicated in cardiovascular processes and may play a role in the development of coronary artery disease in an individual.

“We hope this resource will enable others to investigate the complex mechanisms of coronary disease in different cell types and model systems,” says Miller. “This work would not have been possible without interdisciplinary collaboration and study participants, and we look forward to extending similar resources to the cardiovascular community.”

Source: Eurekalert



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