Unexpected discoveries in human genome
19 February 2008
When the first draft of the human genome was completed, Sir John Sulston argued that it was a beginning not an end. The wave of unexpected discoveries that have followed have vindicated that view. And it is fitting that the Wellcome Trust Sanger Institute has been at the forefront of efforts to understand the genome - as illustrated by its work on conserved regions and copy number variation.
The ENCODE (Encyclopedia of DNA Elements) project is an international collaboration analysing in detail 1 per cent of the human genome. This analysis has thrown up a whole host of surprising findings - from the unexpectedly large proportion of the genome copied into RNA to the seemingly almost random distribution of gene control regions. The ENCODE project, to which Sanger Institute researchers Dr Manolis Dermitzakis and Dr Tim Hubbard made key contributions, is challenging received wisdom about how genes and genomes are organised - highlighting how much is still to be learned about genome function and evolution.
Last year, Dr Matt Hurles and colleagues discovered surprisingly high levels of copy number variation - blocks of DNA present in different numbers, or missing entirely, in different people. Further analysis by Dr Dermitzakis, Dr Hurles and colleagues has revealed that copy number variation does not necessarily correlate with another source of human genetic variation, single nucleotide polymorphisms (SNPs). Hence SNP-based searches for disease-linked variants may miss out on predispositions caused by changes in copy number.
And research continues to identify conditions influenced by copy number variation. In an unusual recent case, Professor Tim Aitman and colleagues discovered a link between copy number variation affecting the FCGR3B gene and susceptibility to autoimmune diseases - but only those affecting the whole body rather than specific organs.
Further reading
- ENCODE Project Consortium. Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 2007;447(7146):799-816.
- Stranger BE et al. Relative impact of nucleotide and copy number variation on gene expression phenotypes. Science 2007;315(5813):848-53.
- Fanciulli M et al. FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity. Nat Genet 2007;39(6):721-3.