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HUGO 2013, Part 1: What does it all mean?

Kahlil Lawless
| Apr 18, 2013
HGP Image

After several days of fascinating and varied talks by a multitude of talented researchers at the Human Genome Meeting/International Congress of Genetics, my head is swimming – and I doubt that I’m the only one. Midway through the conference, we celebrated ten years since the Human Genome Project was officially completed. At the time, this milestone was heralded as the dawn of the genomic era where researchers and clinicians would be able to leverage this new level of understanding to produce incredible discoveries, and deliver significant benefits to the world. Ten years on and the discoveries have been incredible, but once again we appear to have underestimated the phenomenal complexity of biological systems and our ability to understand and manipulate them. Our fancy new tools and databases have unleashed upon us a tsunami of new information, and the question on everyone’s lips is – what does it all mean?

Sample Size of One

The first setback was coming to the realisation of how limited a resource our Human Genome reference sequence actually is, and the emphasis here is on the singular – it is one genome, compiled from several different individuals. The diversity of Earth’s 7 billion humans is not represented in this database, and the more distantly related a person is from this reference, the less useful it becomes. This problem has spawned duplicate genome projects the world over. In our region, the Pan-Asian Population Genomics Initiative (PAPGI) has tackled this issue with gusto, with collaborators from the middle east to south east Asia and everywhere in between have been generating vast datasets and public resources that will become critical reference and research tools1.

Dotting i’s and Crossing t’s

A second potential source of concern is that the human genome reference, even after 19 consecutive revisions, has proved a moving target. Each time it gets better, but still errors remain. Stephan Schuster’s presentation on the RP11 genome assembly showed more than 80 new regions not found in the reference, some containing whole genes.

We Are Not Alone...

One of the hottest emerging fields is metagenomics, as evidenced by a standing room only crowd at the HUGO session to hear Martin Hibberd proclaim that the “future is biomes”. He demonstrated a strong link between diseases such as Age-Related Macular Degeneration and eye flora, while others such as Kyu Young Song from Korea set themselves on a course to understanding the role of microbial genomes in complex diseases such as Inflammatory Bowel Syndrome (which I don’t need to see any more photos of– thank you very much).

DNA is History

Literally. The history of an organism, or even of a single cell, is indelibly inked on its DNA. Julian Parkhill from the Sanger Institute presented his sequencing results on cholera strains for the last 100 years. He was able to show that rather than independent environmental events leading to regional epidemics, virtually all strains could be traced back to strains emerging from south Asia. This analysis showed conclusively that the cholera outbreak in Haiti was not the result of earthquake-damaged sanitation systems, but rather the arrival of Nepalese peacekeepers stationed upstream of Haiti’s main river. He also demonstrated this on a smaller scale tracing transmissions of methicillin-resistant Staph aureus (MRSA) in a hospital outbreak in the UK2. On a smaller scale, the mutational variants that make such analysis possible can also be tracked within an individual over time.

Patrick Tan used comprehensive understanding of the rates and types of somatic mutation to plot the accumulation of variation within a single lifespan, and to pinpoint sudden mutational events that are significant contributors to cancer. Through studying mutation types and frequencies, they were even able to elucidate which mutagens individuals had been exposed to, and determine if these exposures were the causative agent in particular cancers. Needless to say, from here I’m now going to studiously avoid Chinese herbal remedies that may contain wild ginger, as aristolochic acid appears to confer a cancer risk equivalent of smoking ten packs a day... 

One Man’s Junk is Another’s Treasure

Geneticists have been eating their words ever since the day when 99% of the genome was proclaimed to be ‘junk’ DNA. This should have become apparent the moment we found out the human genome only had 20,000 genes, far less than anyone expected. Since then, researchers have identified GWAS loci where there were no genes at all, alternative splicing, antisense, small and long non-coding RNA, DNA methylation, a multitude of chromatin regulation mechanisms, DNA-DNA interactions….the list goes on. With the benefit of hindsight, we now say “it’s not the number of genes, it’s what you do with them”, and the study of gene regulation has risen to the fore.

As John Mattick said in his talk on long ncRNA and their role in disease, “the human genome is a zip-file extraordinaire”. Decoding this is proving much more challenging than sequencing the DNA itself. Regulation is dynamic, responsive, and often unpredictable. Due to perennial changing state of organisms, and the myriad of regulatory mechanisms in play, applying a reductionist scientific approach to regulation has proved a significant challenge.

Understanding these systems requires cross-disciplinary approaches, and at HUGO this year it wasn’t uncommon to see a talk employ everything from DNA-Seq, RNA-Seq, ChIP-Seq, proteomics, microscopy, genetic engineering and everything in between to gain an understanding of a single mechanism. Joseph Takahashi’s 20-year journey to understand mammalian cellular circadian rhythms illlustrates the intense cross-disciplinary paths that lead to success.

So, Why do We Care?

At some stage, we all hope this understanding can be applied in some useful manner (at least that’s what the funding bodies are hoping, otherwise I’m sure none of the presented work would ever have been done). That was the other half of HUGO this year, and comprised many success stories from the world of applied genomics, and how the tsunami of data can be ridden successfully into clinic beach while avoiding the submerged rocks of misdiagnosis and treatment. Stay tuned for my post on HUGO Part 2 – What is it all for?


  1. Ranganathan S, Tongsima S, Chan J, Tan TW, and C Schönbach (2012) Advances in translational bioinformatics and population genomics in the Asia-Pacific BMC Genomics 13 (Suppl 7)S1.

  2. Harris SR, Cartwright E, Tӧrӧk ME, Holden M, Brown N, et al. (2013) Whole-genome sequencing for analysis of an outbreak of methicillin-resistant Staphylococcus aureus: a descriptive study. Lancet Infectious Dis. 13(2) 130–136.

  3. Image courtesy of US Department of Energy Genome Program’s Biological and Environmental Research Information System