New DNA sequencing technology used to correctly diagnose genetic disease

A team of researchers at the Howard Hughes Medical Institute (HHMI) has become the first to successfully diagnose a patient through the use of a high-throughput DNA sequencing technology.

The clinical use of this new DNA analysis technique was reported in the journal Proceedings of the National Academy of Sciences. The new sequencing technology allows rapid, selective analysis of the one per cent of our genome that encodes proteins, otherwise known as our 'exome'. 85 per cent of mutations known to have major clinical implications reside within this exome.

The technology utilises microarray technology to separate the exome from the rest of the genome. By applying a DNA sample to a microarray chip, which contains 180,000 fragments of DNA sequences, the protein encoding regions will stick to their matching fragments on the chip. The 'non-stuck' DNA can then be washed away and the 'stuck' DNA analysed for mutations.

Once Richard Lifton and his team at the HHMI were satisfied that the technology yielded accurate results and could find mutations amongst the 34 million base pairs that make up the exome, they tried out the protocol on a blood sample taken from a five month old Turkish boy suspected of having Bartter syndrome: a rare and potentially life threatening disease in which the kidneys fail to absorb salt, potassium and water correctly. Exome analysis found the boy had gene mutations that cause congenital chloride diarrhoea, a disease where the gastrointestinal tract fails to absorb chloride and water correctly. Without this new DNA analysis the patient would not have got the correct diagnosis.

'I think in the coming years we're going to see a dramatic increase in the use of this kind of technology', says Lifton.

There is some concern that using this technology for diagnosis would be too time consuming and the results would need specialist analysis. However Lifton does not think this should be an issue: 'This is really not the case, it is really quite straight forward to perform and interpret'.

The team hopes their technology will offer a way to speed up the identification of new mutations. 'In genetics now we're quite good at finding mutations where we are able to pinpoint the location of a disease-causing gene because it is present in many family members, but we haven't a good method to find mutations that arise anew in an affected child of unaffected parents, the ability to sequence all the genes will enable one to find these new mutations and link them to disease', said Lifton.