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THE human genome may be almost completely sequenced, but it鈥檚 still throwing up a few surprises. Italian researchers have discovered a new type of mutation that could cause a wide variety of diseases.

鈥淣o one could have predicted this phenomenon by computer or any analysis,鈥� says Francisco Baralle of the International Centre for Genetic Engineering and Biotechnology in Trieste, whose team made the discovery. 鈥淚t has really changed our thinking.鈥�

To create a protein, cells make an RNA copy of the instructions encoded in DNA, and then use this to make the protein. But before these RNA blueprints can be used, 鈥渏unk鈥� sections that don鈥檛 code for any part of the protein have to be removed. These so-called introns are spliced out by a complex molecular machine.

Genetic mutations in the gene being spliced can disrupt the process, with disastrous effects. But all the mutations known to do this lie either within the coding sections or at their edges. The rest of the introns themselves weren鈥檛 thought to affect the process. At least, not until Baralle and his colleagues started studying a splicing defect in a gene called ATM. This mutation affects the brain and immune system, and also predisposes people to cancer.

To their surprise, the defect lay in the centre of an intron, where four 鈥渓etters鈥�, or nucleotides, had been deleted. The mutation stops the splicing machinery from binding to the intron, which somehow causes the intron to be included in the final RNA.

The work reveals another level of complexity in the splicing machinery, says James Manley, a splicing expert at Columbia University in New York. 鈥淚 think we will see these kinds of mutations more and more as we look more carefully,鈥� he says.