The 13-year project to read the entire genetic code of a human being is now complete, say the scientists involved. A detailed analysis of the final human genome 'gold standard' sequence appears in the latest issue of the journal Nature. Surprisingly, it reveals that the estimated number of genes has fallen again, to 20-25,000, from the 35,000 in the version published last April. The latest study provides 'the clearest picture yet' of our genetic make-up, according to Francis Collins, head of the US human genome effort.
At the start of the Human Genome Project (HGP), most scientists thought that the human genome would contain around 100,000 different genes. But as the mammoth study got underway, this number has steadily fallen. According to Tim Hubbard, of the Sanger Institute in Cambridge, UK the new, lower figure means that 'each gene can be used in a variety of different ways depending on how it is regulated'. So although we may not have many more genes than the nematode worm (18,000), it is the way in which these genes are used - where and when in the body - that is important. Also, genes are made up of 'sub-units', which can often be put together and combined with parts of other genes in a variety of different ways.
The researchers say the finished product is 99.999 per cent accurate, an error rate of 1 in every 100,000 of the 2.85 billion DNA 'letters', or base-pairs. And there are now only 341 gaps remaining, compared to the 150,000 gaps in the 'rough draft' unveiled in June 2000. But these gaps cannot easily be closed using technology currently available, and will require more research, say the scientists. US scientist Eric Lander said the final genome sequence 'far exceeds' expectations, in terms of accuracy, completeness and continuity. 'It reflects the dedication of hundreds of scientists working together toward a common goal, creating a solid foundation for biomedicine in the 21st century', he added.
As well as a more accurate estimate of the number of human genes, the new study also sheds light on the phenomenon of duplicated regions of the genome, some of which are involved in disease such as Williams syndrome, Charcot-Marie-Tooth and DiGeorge syndrome. It looks as though such 'segmental duplications' account for about 5.3 per cent of the human genome, more than twice the proportion present in the genetic code of the mouse. Many scientists think that these large DNA duplications played an important role in evolution, providing 'raw material' in the form of copies of existing genes.
Some of the challenges now facing researchers include the identification of genetic variations that cause disease, finding out how all our genes are controlled, and working out how genes and proteins interact with each other in the body.