Part 2 of a 6-part series
The DNA sequence of the human genome is an iconic breakthrough in biology.
Originally released more than 10 years ago, it has fuelled many advances in human health and disease.
Surprisingly, though, the genome sequence is not complete, and work by Massey University senior lecturer Dr Austen Ganley is helping to fill in important gaps in the human genome.
These areas were originally left out of the human genome sequence because they were thought to be difficult to find the sequence of.
"Its like a giant jigsaw puzzle where some parts are difficult to do, so they are just left unfinished," Dr Ganley said. "We thought it was time to revisit them."
In research published in the leading journal Genome Research, Dr Ganley's research group and collaborators at the National University of Ireland, Galway, have for the first time filled in key gaps in five human chromosomes.
Filling in the missing regions involved painstakingly recreating the sequences - strings of the DNA "letters" A, G, C and T - from fragments of DNA. Despite the anticipated problems, the work went smoothly.
"There was only one region that we had real trouble with," Dr Ganley said.
The sequences were now publicly available for anyone to use.
Together, these new sequences account for 0.1 per cent of the total human genome.
"While this may not sound like much, it is still more letters than in the complete Lord of the Rings collection - but the reason that we targeted these sections is because we think they are important for disease, particularly cancer."
The connection with cancer comes from what these regions do.
Special parts of our cells, called nucleoli, have an altered appearance in many cancers, something that has been known for over 100 years.
Such nucleolar alterations are still used as a cancer diagnostic today.
The missing regions targeted by Dr Ganley and co-workers direct the formation of these nucleoli, therefore they may be involved in cancer.
"We suspect that mutations in these regions lead to the nucleolar alterations seen in cancer, and hence may be a cause of cancer," he said.
"Thus it's astonishing that these regions were ignored for so long. Now that we have these sequences, we can investigate what role they play in cancer."
The researchers are now looking at this.
"We are looking for cancer-associated mutations in these regions because if we find some, we might be able to use them to develop novel anti-cancer drugs", said Saumya Agrawal, a Massey University PhD student in computational biology who worked with Dr Ganley and did most of the computer analyses.
The international collaboration arose from a chance meeting between Dr Ganley and Professor Brian McStay, one of the world leaders on nucleoli, at a scientific conference in Germany.
"We agreed that medical science could really benefit from the sequences of these regions, therefore we decided to use our complementary skills to get them," he said.
The Massey University research team focused on the computer analyses, while the Irish group concentrated on the way these regions behave in cells.
The study, which was funded by the Auckland Medical Research Fund, the Royal Society of New Zealand, and Massey University, is a part of Dr Ganley's research programme on the Albany campus looking at the effects of this region of the genome on several aspects of human health including cancer, ageing, and chromosome inheritance.
Dr Ganley expects this work to attract international attention to the level of genomics expertise at Massey University.
"There are not many places in the world that are able to meld biological expertise with the computational expertise necessary to carry out world-leading genomics research.
"This work is testament to the strengths we have in this area at Massey University. It is also reflected in Massey's Albany campus establishing a Genetics major for the first time this year, and this new major will showcase the genomics prowess that we have."
Dr Ganley says the work also highlights the importance of bringing highly skilled foreign PhD stu-dents to New Zealand.
"There are very few students in New Zealand with the computer skills in biology to perform this work, and so without Saumya's involvement the project would have foundered."
Full gene picture promises a new era of discovery
Genome research has come along way since the genome - the entirety of an organism's hereditary information - was first sequenced back in 1977.
It took almost 20 years before the first genome of a free-living organism was sequenced, a bacterium which causes human infections, in 1995.
The human genome only took another six years after that to be sequenced, although not completely.
But Dr Austen Ganley believes scientists will be able to complete the genome puzzle within this decade, providing vital information in research areas including cancer and ageing.
Getting the full picture, he said, would allow scientists to make discoveries they could not have anticipated.
"What we do find is likely to be important for our understanding of disease - and therefore health," he said. "For example, there are many diseases that are known to have a genetic basis, but for which we have really struggled to find what these changes are."
The problem was the search was limited to two things: first, we don't yet know our complete genetic make-up, and secondly, we don't understand enough about what genes do and how they are controlled.
"So, at the moment it's a bit like searching for a piece of jewellery someone has dropped in town - the problem is, some of the places they went, you can't go to, and they haven't told you what the jewellery piece they've dropped is.
"The likelihood of success is increased the more places you can search and the more you know. The full picture will remove the first problem, and scientists around the world are working very hard on the second.
"We can't say what diseases, etc this will help us to understand, but we do expect it will help us with something."
• Part 1: Tackling the obesity epidemic
• Part 2 (Today): The human genome
• Part 3: The Kiwi-made biotech wonder
• Part 4: Learning mental time travel
• Part 5: The birth of the artificial muscle
• Part 6: The age of wearable computing