Leiden scientists sequence first female DNA

Following in-depth analysis, the sequence will be made public, except incidental privacy-sensitive findings. The results will contribute to insights into human genetic diversity.

DNA of geneticist Marjolein Kriek
The DNA is that of dr Marjolein Kriek, a clinical geneticist at LUMC. “If anyone could properly consider the ramifications of knowing his or her sequence, it is a clinical geneticist,” says professor Gert-Jan B van Ommen, leader of the LUMC team and director of the ‘Center for Medical Systems Biology’ (CMSB), a center of the Netherlands Genomics Initiative.

Van Ommen continues: “Moreover, while women don’t have a Y-chromosome, they have two X-chromosomes. As the X-chromosome is present as a single copy in half the population, the males, it has undergone a harsher selection in human evolution. This has made it less variable. We considered that sequencing only males, for ‘completeness’, slows insight into X-chromosome varialibity. So it was time, after sequencing four males, to balance the genders a bit”. He smiles: “And after Watson we also felt that it was okay to do Kriek”.

Eight times coverage
The DNA sequencing was done with the Illumina 1G equipment. This has been installed in January 2007 in the Leiden Genome Technology Center, the genomics facility of LUMC and CMSB. In total, approx. 22 billion base pairs (the ‘letters’ of the DNA language) were read. That is almost eight times the size of the human genome.’

Dr. Johan den Dunnen, project leader at the Leiden Genome Technology Center: 'This high coverage is needed to prevent mistakes, connect the separate reads and reduces the chance of occasional uncovered gaps.

Johan den Dunnen: 'The sequencing itself took about six months. Partly since it was run as a ‘side operation’ filling the empty positions on the machine while running other projects. Would such a job be done in one go, it would take just ten weeks”.

The cost of the project was approximately €40.000.- This does not include further in-depth bioinformatics analysis. This is estimated to take another six months.

History
In 2001, the DNA sequence was published of a combination of persons. The DNA sequences of Jim Watson, discoverer of the DNA’s double helix structure, followed in 2007, and later the DNA of gene hunter Craig Venter. Recently the completion of the sequences of two Yoruba-Africans was announced.
Bessensap
The researchers announced their news at the yearly ‘Bessensap’ meeting, bringing together the Dutch scientists and the press. The Netherlands Organization for Scientific Research NWO organizes this event jointly with the Association of Science Writers VWN and Science Center NEMO. In its eight years of existence, Bessensap (www.nwo.nl/bessensap) has had several high-profile news items. It has had a debate with Italian ‘clonedoctor’ Severino Antinori and hosted dino-hunter Jack Horner, who was key in the Jurassic-Park modelling. During Bessensap also the yearly Eureka prize is awarded for the best popular-scientific book and media production.

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