New Atlas Shows How Neurodegenerative Cell Traits are Linked to the Genome

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by Ana Belo |

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Researchers have created an atlas that links a set of genes in the DNA to a particular trait or disease, a tool that may advance understanding of certain cell characteristics in neurological diseases like Alzheimer’s, Parkinson’s and amyotrophic lateral sclerosis (ALS).

This atlas can be further developed and updated by other studies, making the research in the future more visible, up-to-date, and coherent.

The article, “iPhemap: an atlas of phenotype to genotype relationships of human iPSC models of neurological diseases,” was published in the journal EMBO Molecular Medicine.

“The ultimate goal of this research is to be able to determine the phenotypes [physical characteristics of a trait] and genotypes [set of genes in the DNA] relationship in neurological diseases … to find new medications to stop neurodegeneration,” Jaime Imitola, MD, lead author of the study, said in a press release. Imitola is director of the Progressive Multiple Sclerosis Multidisciplinary Clinic and Translational Research Program at Ohio State University’s Wexner Medical Center.

The first cells of a fetus, called embryoid cells, can generate all cells of a human body. While this is helpful for developing therapies, ethical concerns have impaired the use of such cells.

However, researchers have come up with ways of creating embryoid-like cells by reprogramming blood or skin cells in the lab. These reprogrammed cells that are in a pluripotent state can be pushed into becoming any other type of cells of the body. They are called induced pluripotent stem cells (iPSC).

Since iPSCs were discovered nearly a decade ago, hundreds of studies have addressed how genes influence a certain disease trait. But the abundance of information on neurological diseases using pluripotent stem cells has become difficult to follow and interpret.

Also, how research is done using iPSC in neurological diseases varies among different laboratories, Imitola said.

In an attempt to link this information, Imitola and colleagues conducted an analysis of 93 studies, totaling 31 neurological and neurodegenerative diseases. Most studies, however, used iPSCs from Alzheimer’s, Parkinson’s, Huntington’s, or ALS patients, to understand and treat these neurological disorders.

From a total of 243 patients and 214 healthy controls, researchers identified 663 central nervous system cell traits and linked them to a particular genotype. This allowed them to develop a map, which they termed iPhemap, that displayed the links discovered the analysis.

The online map, available to researchers worldwide, revealed that previously unrelated genes lead to the same disease trait. It also showed that changes in gene expression in certain brain regions may lead to disease.

The scientific community can easily update and repeatedly refine and use the information in the database. As a result, the online database will show continuously up-to-date results to all scientific community.

This will help the research community accelerate development of new and more effective therapies.

“Synthesizing this information to understand the phenotypic role of disease-promoting genes and identifying the limitations of our current practices will be crucial steps toward achieving the great translational potential of induced pluripotent stem cell models of neurological diseases,” Imitola said.