PLOS COMPUTATIONAL BIOLOGY, RUTH BARSHIR ET AL.Genes that cause hereditary diseases are often expressed across a wide range of cells in the human body, but the diseases they cause can be specific to a few tissues or organs. Many of these genes are expressed at higher levels in diseased tissues, and their proteins have a significantly greater tendency for tissue-specific protein interactions, according to a study published last week (June 12) in PLOS Computational Biology.
“Together the two factors we identified are relevant for as many as two thirds of the tissue-specific hereditary diseases [studied here],” Esti Yeger-Lotem from Israel’s Ben-Gurion University of the Negev and her colleagues wrote in their paper.
The researchers suggested that these tissue-specific interactions, known as an interactome, highlight disease mechanisms, and can provide an efficient filter to identify causal genes within diseased tissues.
To identify these interactomes, Yeger-Lotem‘s team combined gene and protein expression data for 16 different tissues, such as lung, brain, and breast, with data on protein-protein interactions within each. The researchers found all these tissues shared a core network of nearly 5,000 proteins and more than 26,000 protein-protein interactions.
When they analyzed genes linked to 303 hereditary diseases, the researchers found that over 80 percent of the causal genes were expressed in 10 or more tissues, but these same genes only caused disease in a small subset. Such causal genes were transcribed at higher levels and interacted with more proteins in disease-affected tissues than unaffected ones.
While tissue-specific protein-protein interactions may not be entirely responsible for the disease, they may contribute to its clinical manifestations, according to the authors.
“The distinct features we identified provide a starting point for elucidating the molecular basis of many hereditary diseases,” the authors wrote.