The Future's Genomic

Genome sequencing could ultimately change the face of biology. More immediately, it is likely to change the way scientists conduct their research. With the completion of the working draft of the human genome, the DNA letters (ACGT) that make up our 60 000-100 000 genes are in the public domain, freely accessible to all who want to interpret and exploit the sequence data.

Under the direction of Dr John Sulston, the Sanger Center in Cambridgeshire has contributed a third of the sequence data to the international Human Genome Project. Dr Sulston regards this not only as a scientific milestone but also a celebration of life: "Over the decades and centuries to come, this sequence will inform all of medicine, all of biology, and will lead us to a total understanding of not only human beings but all of life."

Making the most of the 'genomic revolution' is the great challenge for the coming decade and with around 90 per cent of the human genome sequence already available worldwide, the next step is providing the 'gold standard' sequence - filling the gaps and finishing. This will increase overall sequence accuracy to 99.99% or one mistake in 10,000 letters.

Dr Michael Morgan, Chief Executive of the Wellcome Trust Genome Campus considers this to be a natural next step: "The 'Holy Grail' is within our grasp and it would be a tragedy if we stopped at this stage. Until we have got all the sequence from one end to another we won't know exactly how many genes there are."

The genomics revolution is already having a dramatic effect on the way scientists work. With a draft map of the genome readily available, scientists have access to a framework which provides a more rational approach to gene hunting and determining the function of those genes.

"With the working draft now complete, something that takes gene hunters three or four years could happen in a year to a year and a half," says Professor Tony Monaco, from the Wellcome Trust Center for Human Genetics at the University of Oxford.

Once genes are identified, scientists can work from the gene towards function, but at present most genes - probably tens of thousands - remain a mystery. This presents a further challenge to analyse the data and assign functions to genes.

Researchers are already analysing the DNA sequence to identify variations in our genome (known as single nucleotide polymorphisms - or SNPs) which, with the help of the working draft, can easily be spotted: "This will lead to accurate diagnosis of people's propensity for certain disease," said Dr Sulston.

In 1999, the Wellcome Trust and ten pharmaceutical companies formed a joint initiative to identify the common variations in our genes. The SNP Consortium (which now numbers 12 companies and the Trust), one of the first projects set up to exploit data from the human genome project, is pinpointing the subtle genetic differences that predispose some but not others to diseases such as Alzheimer's, cancer and diabetes: "SNPs are a vital research tool," comments Dr Morgan, "which promise to usher in an era of personalised medicine. This will not happen tomorrow but at some point in the near future."

Without the knowledge arising from human genome project, tracking the SNPs would be a difficult task. Similarly, Professor Mike Stratton could not develop his Cancer Genome Project, which aims to identify the genes associated with all forms of human cancer. Set up at the Sanger Center in February 2000, Dr Stratton and his team will compare DNA sequence in cancers against the 'normal' blueprint of the human genome, in a bid to detect abnormal cancer genes: "Ultimately, identification of these genes will highlight the weak points in cancer cells with which we can interfere with and treat the disease," says Dr Stratton.

Allied to identifying SNPs and the cancer genome project, the sequence data will be exploited in the future in a burgeoning area of research called functional genomics - that is, assigning a function to the genome. Our genome is not just about genes, some regions regulate the activity of genes, others help control the accuracy and timing of cell division. One of the aims of functional genomes is to identify these regions and understand how they work.

The human genome project has identified an abundance of new proteins, encoded in the gene sequences. Research has already moved on to an analysis of these proteins.

Researchers are using computing technologies to try to predict the 3-D structure of proteins from DNA sequence. A vital component of this is so-called 'structural genomics', hence the proposal to establish a new UK-based synchrotron, to replace the current facility which is fast becoming obsolete.

A synchrotron is an extremely powerful large X-ray machine, which emits very bright beams of light. It is these beams which make it possible to identify the structure of molecules. In the case of proteins, such knowledge is invaluable in the design of drugs that influence the action of the protein.

Completion of the working draft is the end of the beginning and Dr Sulston stresses that we should not underestimate this event in human history: "In a sense this can be compared with putting man on the moon, which illustrated our power and understanding. In the same way with the human DNA sequence, it's a bit iconic - we are celebrating our understanding of life."

Completion of draft human genome:

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