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Liverpool Pair Identifies Common Genetic Modifiers of Neurodegeneration

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Combining data from more than two dozen studies of three model organisms, the University of Liverpool's Bob Burgoyne and Xi Chen identified common genetic modifiers of neuro-degenerative disease — including 34 genes shared across Caenorhabditis elegans, Saccharomyces cerevisiae, and Drosophila melanogaster that also have human orthologs.

"We had been studying a model for neurodegeneration in C. elegans, and wanted to get a full understanding of what key regulatory genes had already been identified [in other organisms] to feed the information into the design of our own study," Burgoyne says. "From previous work on model organisms, it seemed that there was only limited overlap between studies on different disease models."

Because of this, he and Chen were surprised to find as many as 34 overlapping genes among the three model organisms in their analysis. Aware that many, if not most, of those genes might not have human orthologs, Burgoyne and Chen analyzed functional data for each, expecting to find a reasonable degree of species-specificity among them. They were surprised to find that all 34 had human orthologs. "This is very reassuring, as it supports the idea that the model organisms may indeed be providing clues relevant to the human neurodegenerative diseases," Burgoyne says.

Some of those 34 genes that showed cross-species overlap are well conserved and have been widely studied, Burgoyne adds, while "a number [had] not previously been specifically studied to any extent in the context of neuro-degeneration."

He says that this type of integrative analysis may be amenable to other diseases that have been studied in multiple model organisms.

Going forward, Burgoyne and Chen intend to follow up on this study, published online in advance in BMC Genomics in February, "with [a] more detailed investigation into our C. elegans model of some of the less-studied examples from the list of 34 overlapping genes."

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