The decoding of the first Irish genome represents a significant advance in the quest to understand the link between genetic variation and disease susceptibility on this island.
This places the Irish genetic code in the public domain for the first time and permits it to be compared with mappings of the codes of other population groups.
This is important as it is only by comparing the genome with other sequences that scientists can hope to isolate a specific “Irish genetic signature”, and to understand the genetic basis of our susceptibility to certain diseases.
A principal reason for sequencing Irish DNA was that it was not represented in any of the large genomic studies under way, explained the Irish project’s originator Prof Brendan Loftus of University College Dublin’s Conway Institute.
“Certain gene variants can become locked in a population due to factors like geography. Irish people’s genes mirror the island’s peripheral location in Europe, which makes it an interesting subgroup to sequence,” Prof Loftus said.
“Some 13 per cent of the variation we uncovered has not been seen before. It’s likely that some of that variation is specific to the individual and some is more diagnostic of him being Irish. We will only find out which is which over time.”
A Mayo-born graduate of Dublin City University, Prof Loftus spent the 1990s working in the US under the well-known Craig Venter, collaborator on the first human genome sequencing project completed in 2003 at a cost of €2.7 billion.
In contrast with the original human genome project, the Irish project was carried out with the resources of a small lab over about 13 months and at a cost of €30,000.
Prof Loftus said the project illustrated how rapidly the accumulation of genomic information on a population level can be generated.
But he acknowledged that while the capacity to generate the sequence data is proceeding at pace, the rate at which the data can be reliably interpreted has lagged behind.
One area where genetic sequencing is likely to play a major role is in patient response to medication.
“The majority of blockbuster drugs, from aspirin to cancer medication, don’t appear to work on significant sections of the population,” said Prof Loftus.
“There is a big thrust in the medical community towards personalising medicine and nutrition because people respond in different ways to the same product.
“And one of the most likely reasons for this is their genetic background. The drug companies are interested to see who these people are, and to find out if they will respond to variations of the existing drug compounds.”
Since the first human sequence was generated in the US in 2003, between 20 and 30 full human genome sequences have been published.
However, the rapid acceleration in DNA sequencing technology in recent years has seen a proliferation of projects, with more than 100 separate projects in progress.With the cost of sequencing dropping all the time, experts maintain it won’t be long before people will be carrying around parts of their genome on a USB key.
US company 23andMe, established by Anne Wojcicki – wife of Google founder Sergey Brin – already offers to sequence portions of the genome using a sample of saliva, for as little as $350.
Dr Gerard Cagney, principal investigator in functional genomics at the Conway Institute, said representative species from all branches of the tree of life – bacteria, fungi and plants, along with animals ranging from worms to insects and from fish to monkeys – are now being sequenced daily.
“Nevertheless, the technical difficulty associated with sequencing a small virus like HIV, containing some 9,000 units of DNA, pales in significance next to the challenge of sequencing a human genome, composed of more than three billion units.
“The problem is compounded by the fact that the entire sequence is assembled from short individual sequence fragments – typically less than 200 units – so the final product is similar to piecing together a huge jigsaw puzzle, and requires the work of computer scientists and statisticians,” Dr Cagney said.
“There are also large regions of repeated sequence in human genomes and their biological significance is still not fully understood.
“The sequencing process therefore relies partly on comparison with other known sequences, and it is for this reason that reading an Irish genome is significant.
“It can be used to place Irish genes in the context of worldwide human genome diversity.”
