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In their experiment, Seidman and his colleagues discovered more than 700 genetic discrepancies between their two samples, compared with about 50 found using traditional screening methods. “We’re pretty sure it’s a big deal,” says Seidman. “These mutations lead to a thickening in the heart wall, and also cause muscle cells to die, and also cause cardiac arrhythmias. And we had thought that probably one followed the other. But now we think there are probably three different pathways activated for each process. And we think this method would be very useful for distinguishing those.”

However, some scientists, like Silke Sperling, a cardiovascular geneticist at the Max Planck Institute for Molecular Genetics, warn against overinterpreting such results. “To date, the importance of genes with very low RNA levels is unclear in general,” says Sperling. “[Also], the individual variability of gene-expression profiles even between litter mates in mice is quite high, and to make a general causative biological assumption, the analysis of several mice is required.”

Seidman acknowledges this risk. “It’s absolutely true that if you see an RNA go up or down, you don’t know if RNA is the cause of the disease or the result,” he admits. But, he says, further studies could help clarify the roles of the RNA.

Down the road, Seidman also sees applications for the new technique in better diagnosis of other diseases such as different types of cancer. Scientists have already shown that “some changes in RNA expression were diagnostic of a particular type of tumor. If we could measure all RNAs, that might allow for further stratification of tumor types.”

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Credit: Jon Seidman

Tagged: Biomedicine, DNA, genetics, disease, tumor, RNA

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