Finding a cure for many genetic diseases — including some cancers and neurodegenerative ailments — may be much more complicated than previously thought, new research indicates.

An international team's work on alternative splicing, the process that produces 75,000 of the proteins in human cells, found that small changes in the environment near an alternative splice could produce a large change in the proteins produced.

That's important, because mutations in DNA sequences in alternative splicing cause more than half of all genetic diseases.

If the materials used in splicing are seen as forming a long sentence, then the individual parts can be considered words, said Tim Nilsen, director of the Case Western Reserve University School of Medicine's Center for RNA Molecular Biology in Cleveland.

"Adding or deleting one word," he said "can radically change the meaning of the sentence."

Biologists believe that rules hidden in the DNA code control alternative splicing, so once the code is broken, cures can be found for genetic diseases.

But the finding by Nilsen's team on the importance of the environment means the code is much more complicated than thought. That will likely delay progress by scientists who hope to amend the code to cure genetic diseases, said Joseph Nadeau, chair of the medical school's genetics department.

"It's context, not [genetic] code, that's important," he said.

The study, Dynamic regulation of alternative splicing by silencers that modulate 5' splice site competition, was published in the Dec. 24 issue of Cell.

Nilsen led a team from three U.S. institutions — Case Western, Columbia University and the Memorial Sloan-Kettering Cancer Institute — and the Max Planck Institute for Biophysical Chemistry in Germany.