April 25, 2020

Why do diseases such as COVID-19 and cancer hit some people harder than others?

By Susan Murphy

As the nation marks DNA Day on April 25 — commemorating the discovery of DNA's double helix in 1953 and the completion of the Human Genome Project in 2003 — Mayo Clinic researcher Nicholas Chia, Ph.D., continues to search for answers to the question of why some people are more susceptible to getting a severe disease than others. A major clue can be found in DNA, the genetic code inside every cell in the body that carries the blueprint of life.

“We realize the genome — a person’s complete set of DNA — is just a blueprint,” says Nicholas Chia, Ph.D., the Bernard and Edith Waterman co-director for the Mayo Clinic Center for Individualized Medicine Microbiome Program. “But a blueprint doesn't tell you how a building is used. It may tell you how many people the kitchen could support and that it has 25 bathrooms, but you don't really know how exactly that building is used.”

Every person has their own unique sequence of DNA, composed of twisting paired strands that carry instructions needed for an organism to develop, survive and reproduce. DNA passes hereditary information from one generation to the next, such as skin, eye and hair colors, but it can also pass down susceptibility to diseases and genetic mutations, including those acquired in a person’s lifetime.

Taking a deeper dive into multi-omics

Mayo Clinic has spent decades exploring and sequencing the human genome, allowing doctors to tailor a range of therapies to a patient’s genes, including for hard-to-treat cancers and rare diseases. Now, they are also going a step further and focusing on “multi-omics” data in their search for answers, including proteomics (study of proteins in a cell), microbiome (study of bacteria, fungi, protozoa and viruses that live inside the body) and metabolomics (study of chemical processes) to identify the underlying causes of diseases.

Dr. Chia says taking a deeper dive into multi-omics and researching beyond DNA — into the RNA, metabolites and proteins — can paint an even more detailed picture to help uncover medical mysteries. 

“The RNA, the proteomes, the microbiome, the metabolites tell you what is actively being turned on and off,” he explains, “What is actually happening enzymatically, what your environmental exposures are and what metabolites are being exchanged. These are all really important elements because they are part of how we molecularly behave and they define our biological state, which defines our state of disease.”

Dr Chia says DNA defines a person’s potential to get disease, but it does not define the disease itself. He references a bacterial infection as an example. 

“A bacterial infection is explained by your exposure to a certain bacterium,” he says. “It's explained by your microbiome not protecting you against that bacterium. It's explained by how your immune system reacts to that bacterium. It's explained by the inflammation, the fever, and by specific actions and specific subsets of cells. We're trying to understand all the variation, how all the parts come together.”

Autoimmune diseases and the microbiome

Some of Dr. Chia’s other research is centered on autoimmune diseases and the relationship with the microbiome. He says when this population of bacteria is disrupted, it can lead to serious health problems. 

“The premise of an autoimmune disease is that part of your immune system is somehow attacking part of your body,” he says. “One-third of those patients don't actually have an autoimmune disease — they're reacting to something in their microbiome. It could be a virus, a bacteriophage, a virus that infects bacteria, it or could be a bacteria.”

 Dr. Chia is looking forward to the day when researchers will be able to wipe out a third of autoimmune disease by doing micro-biomedicine to alter the microbiome.

According to Dr. Chia, DNA sequencing contributes a wealth of knowledge, but researching beyond DNA to advance discoveries and diagnostics has the potential to transform human health.

Tags: cancer genomics, DNA, education, genomics, microbiome, Microbiome, rare disease, Research, Uncategorized

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