Published online: 10 August 2006; | doi:10.1038/news060807-15 Another source of genetic variability mapped Researchers chart out insertions and deletions in the genome.Richard Van Noorden The way that some pieces of DNA are chopped and changed within individual genomes has been mapped for the first time. The catalogue of insertions and deletions in the human genome could eventually help scientists to find treatments for diseases, tailored to the genetic makeup of individuals.
We share some 97 to 99% of our DNA in common. The remaining 1 to 3% in the 'book of life', the human genome, reads differently in every individual. These small DNA variations explain the differences between us: from our physical appearance, to whether we succumb to specific diseases.
Differences in single chemical bases — the 'letters' of the genome — are the most common type of genetic variation. These differences are called single nucleotide polymorphisms (SNPs, pronounced 'snips'). SNPs are well studied: some 10 million have been found in the human genome.
But our genomes don't just vary at these single points; there are larger structural variations as well. Chunks of DNA can be found inserted or deleted in different places in different people's genomes. Whether these chunks are one base or thousands of bases long, they are collectively known as INDELs. The insertions and deletions come in several different classes. For example, transposons are genes that jump around within the genome; in other cases, multiple copies of the same bit of DNA get inserted.
Snipped out
Scott Devine, of the Emory University School of Medicine in Atlanta, Georgia, and his team set out to study INDELs by looking at genome information from 36 people around the world, which was originally collected to find SNPs. They have now found and mapped more than 400,000 unique INDELs, and expect to identify 1 or 2 million in total within a year.
The search itself just requires sophisticated software to crank through the codes. "The method for finding these genetic variants is relatively cheap, since the sequencing has already been done," says Lisa Brooks of the National Human Genome Research Institute in Bethesda, Maryland.
The team's first efforts will be published in the journal Genome Research in September, but have already been posted online on the publicly available SNP database.
In addition to INDELs, even larger, giant deletions of several hundreds of thousands of bases have recently been found to exist, as well as reversions of portions of DNA.
Mapped to health
All these genetic variations tend to be associated with diseases — or point the way to the region of a chromosome that makes a person prone to a particular disease.
For example, cystic fibrosis is often caused by a deletion of three base pairs, whereas the repeat number of another triplet of base pairs is important in Huntingdon's disease.
About a third of the INDELs mapped by Devine's team so far have been found to lie within genes rather than in the DNA that doesn't code for proteins, so would be expected to have some sort of effect.
"We need to figure out which changes correspond to changes in human health," says Devine. Then, at some future time, one large map of genetic variation and its effects could predict the expected health of any one person. Based on that person's individual genome, particular health treatments could be recommended.
For the moment, the focus is on integrating the INDEL map with other maps of genetic variation. The HapMap project, for example, helps researchers studying disease by grouping those SNPs that are linked, so inherited together as a block (a 'haplotype'). Instead of running through 10 million individual SNPs to find which is associated with a disease, a researcher need only examine the far fewer number of 'tag' SNPs that identify an entire block.
If the same exercise could be done with INDELs, researchers would be a step closer to obtaining a unified map explaining all human variation.
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