A new study, published in the journal Nature, has mapped the genome of eight individuals and revealed large regions of genetic variability. An international collaboration led by Evan Eichler at the Howard Hughes Medical Institute compared the genome of four African, two Asian, and two European individual against the reference DNA sequence from the Human Genome Project, and identified large segments of DNA that were variable between individuals, from thousands to hundreds of thousands of base pairs long. A base pair is one 'chemical letter' of DNA code. This study illustrates the complexity of the human genome at the structural level, and the variability identified may lead to new genetic associations with diseases such as autism, diabetes, heart disease, and epilepsy.
The researchers identified nearly 2326 sites of structural variability in the genome: the deletion, insertion, inversion, or multiple copies of large segments of DNA or genes. At some sites, the DNA of each individual was different, while at others only some individuals varied. Fifty per cent of the DNA segments were previously unrecognised as areas of large variability within the genome, and 525 of the identified DNA segments were absent from the original HGP reference genome. 'These results strongly argue that the human genome sequence is still incomplete,' Eichler concluded, adding: 'This represents uncharted territory that can now be examined in more detail to determine the function of these new segments of the human genome with respect to disease and gene activity.'
Sites of small scale, single base pair genetic variation have been well characterised in the human genome, and these are used in clinical applications detecting the genetic risk of disease. Previous studies have also described the existence of mechanisms for the large-scale genetic variability, without describing their exact location or frequency in the genome. In this research, Eichler and his colleagues developed a new sequencing technology, and succeeded in systematically mapping the whole genome of the eight individuals, identifying what type of genetic variability exists at which sites within the human genome. Eichler stressed that high quality genetic mapping was key to identify these large structural differences between individuals. In the research paper, the authors speculated that this new technique would be a 'prelude to future individual genome sequencing projects', an additional tool in building more comprehensive maps of genetic variability in individuals.
Why some sites within the genome are prone to large-scale changes between individuals is currently not understood, but researchers believe that the sites are unstable or rapidly evolving. Regions of high copy numbers of genes are more prone to genetic variability. The new genome maps will be a valuable resource for the genetics community, and will allow researchers to investigate the processes that shape the human genome and human evolution, and may lead to new genetic associations with disease.