New research from 13 different research centres in Britain and the US has revealed an unsuspected amount of variation between each individual's DNA. The research, published simultaneously in the journals Nature, Nature Genetics and Genome Research gives a much more comprehensive picture of human genetic variation, and may allow scientists to determine why different individuals are more susceptible to certain diseases.
Our genome operates by sending instructions from DNA in the form of mRNA for the manufacture of proteins. The first studies of the human genome indicated that one person's DNA was likely to be 99.9 per cent identical to that of another. The differences were caused by single base changes called SNP (single nucleotide polymorphism) which can cause small changes in the proteins that DNA codes for.
In the 1990s scientists discovered that people also differed in the number of copies of genes they had, and that large sections of an individual's genome could be duplicated many times over, or be completely absent in others. It was known that these duplications, called copy-number variants (CNV's) could cause disease in some cases, for example, varying copy numbers of the globin genes were shown to be responsible for various disorders such as alpha-thalassaemia. However these duplications are difficult to sequence, due to their repetitive nature, and were given less attention than the other regions of our genome which were considered to be more interesting.
New studies of the human genome have now revealed much more variation than previously suspected in the number of copies of genes a person has, which may explain many of the differences observed between individuals. The studies suggest that variation in the number of copies of genes is normal, but many diseases may be triggered by the loss or gain of copies of certain key genes.
Stephen Scherer at the Hospital for Sick Children in Toronto and his team looked for differences in deleted or duplicated chunks of DNA in the two human genome sequences completed to date and found that almost 24 million bases are involved in CNVs. He said this meant 'significantly more variation exists between humans than was previously estimated'.
At the same time, Matt Hurles at the Wellcome Trust Sanger Institute in Cambridge compared the genome of 270 people in four ethnic groups and measured the number of copies of genes. They managed to document almost 1,500 variable regions covering 12 per cent of the human genome, including hundreds of genes and other functional elements. More than half the CNV's they identified overlap known genes, making it likely that CNV's can play a role in complex diseases. If deletions or duplications are present within a gene or its regulatory region this could cause an imbalance in the level of mRNA and subsequently protein production from that gene. For genes and pathways where the amount of functional protein is crucial, CNV's could provide variation in disease susceptibility.
Charles Lee, another of the project's leaders at Harvard Medical School in Boston, told the Independent 'Many examples of diseases resulting from changes in copy number are emerging...including Parkinson's Disease and Alzheimer's'. He said the new research could be 'combined with pre-existing data to provide a much more comprehensive understanding of genetic variation'.