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Nature: Milestones in Diabetes Research based on 520K genome samples
Nature: Milestones in Diabetes Research based on 520K genome samples. The researchers performed the largest GWAS to date for type 1 diabetes, analyzed 520,580 genome samples, and identified 69 new associated signals. Then, they located 448,142 cis-regulatory elements (non-coding DNA sequences within or near genes) in the pancreas and peripheral blood cell types.
By mapping the genetic basis of diabetes, researchers at the University of California San Diego School of Medicine determined the predictive causality of specific cell types in type 1 diabetes.
The results of the study will be published in the online edition of Nature on May 19, 2021.
Type 1 diabetes is a complex autoimmune disease characterized by damage and loss of insulin-producing pancreatic beta cells, followed by high blood sugar (hyperglycemia), which is harmful to the body and may cause other serious health problems. Such as heart disease and decreased vision. Type 1 diabetes is less common than type 2 diabetes, but its prevalence is rising. Currently, there is no cure, only disease management.
The pathogenesis of type 1 diabetes, including how autoimmunity is triggered, is currently unclear. Because it has a strong genetic component, a large number of genome-wide association studies (GWAS) have been carried out in recent years. Researchers have compared the entire genomes of people with the same disease or condition, looking for genetic codes that may be related to the disease or condition. The difference.
In the case of type 1 diabetes, the identified risk variants are largely found in non-coding regions of the genome. In the latest study, Dr. Kyle Gaulton, assistant professor of pediatrics at the University of California, San Diego School of Medicine, and his colleagues combined GWAS data with epigenome maps of peripheral blood and pancreatic cell types. The epigenome map describes in detail how and when genes in cells are turned on and off, which determines the production of proteins that are essential to specific cell functions.
Specifically, the researchers performed the largest GWAS to date for type 1 diabetes, analyzed 520,580 genome samples, and identified 69 new associated signals. Then, they located 448,142 cis-regulatory elements (non-coding DNA sequences within or near genes) in the pancreas and peripheral blood cell types.
Gaulton said: “By combining these two methods, we can identify the cell type-specific function of disease variants and discover the predictive causal role of pancreatic exocrine cells in type 1 diabetes, which we can verify through experiments.”
Enzymes produced by exocrine cells of the pancreas are secreted into the small intestine to help digest food.
Co-author Maike Sander, MD, said these findings represent a major leap in the understanding of the causes of type 1 diabetes. She described the work as “a landmark study.”
This means that the dysfunction of exocrine cells may be the main cause of the disease. This study provides a genetic roadmap from which we can determine which exocrine genes may play a role in disease pathogenesis. “
(source:internet, reference only)