Optimal recognition of 'true' genetic differences

Despite advanced genome technologies, it remains a major challenge to identify small variations between the hereditary material (DNA) of different individuals.

VIB scientists connected to the K U Leuven and the University of Antwerp describe in Nature Biotechnology a method that makes it possible to trace genetic variations in the DNA with a high degree of certainty when using short-read sequencing technologies by Complete Genomics and Illumina.
Joke Reumers of Diether Lambrechts’ research group (K.U.Leuven) and Peter De Rijk from Jurgen Del-Favero’s group (University of Antwerp) developed a strategy and accompanying software to quickly find genetic differences between two or more genomes, and they can distinguish errors made during the reading of the genomes.
The method was then applied in two studies in which the first ever Flemish genomes were investigated. First of all, it was possible to characterize the minimal genetic differences between the complete genomes of monozygotic twins. The method was then used on the genomes of a tumor and the normal tissue of a patient with ovarian cancer, making it possible to detect the mutations responsible for the tumor development.
Although the technology to 'read' human genomes is already highly advanced, this does not take away from the fact that it remains a major challenge to find the specific differences between two human genomes. The human genome consists of 3 billion 'base pairs', of which about 3 million differ from the so-called reference genome. Between two similar genomes, for example between two related people or between a tumor and the normal cells of the cancer patient, this number is much lower, on the order of tens to thousands. This is the same order of magnitude as the number of errors that are made when reading the genomes, making it very difficult to distinguish the 'true' differences from the errors.
By comparison, if you were to put the human genome into book form you would have about 700 books of 1000 pages each. It would be hopeless to try to review these books manually. That is why it is of crucial importance to develop a fast method to automatically, efficiently and accurately find the genetic differences between two people.
In June 2000, Craig Venter of Celera and Francis Collins of the Human Genome Project stood together to present the first version of the human genome in the presence of then-president Bill Clinton. Further refinements followed in 2001 and 2004, leading to the first human reference genome. All humans differ slightly from this reference genome, and these very differences partially determine a person’s sensitivity, for example to cancer, heart and vascular diseases, mental development disorders, or specific medication. Over the years, this technology has evolved further, making it now possible to map an individual genome in a few days’ time.
Because this research may generate a lot of questions, we would ask that you cite the email address that VIB has provided for this in your report or article. Everyone can direct questions about this and other medical research here: patienteninfo@vib.be.
For more information, visit www.nature.com/nbt/journal/vaop/ncurrent/abs/nbt.2053.html

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