Δημοσίευση σε περιοδικό – Journal of DNA Repair

Δημοσίευση σε επιστημονικό περιοδικό – Journal of DNA Repair – under review


“Holliday Junctions as distinct recombination units contributing to human microdeletion and microduplication syndromes”

Ladias Paris1, Markopoulos Georgios2, Sakaloglou Prodromos1, Kostoulas1 Charilaos1, Bouba Ioanna1, Markoula Sofia3, Tzavaras Theodore2 and Georgiou Ioannis1
In collaboration with the recombination study Group: Bellos Christos4, Stefanou Konstantinos4, Stergios Georgios4
1. Laboratory of Medical Genetics and Human Reproduction,

2. Laboratory of General Biology

3. Department of Neurology, School of Health Sciences, Faculty of Medicine, University of Ioannina,

4. Lime Technology 54 110 Ioannina, Greece



Holliday junctions are the first recognized templates of legitimate recombination. Their prime physiological role is meiotic homologous recombination, resulting in genetic rearrangements, in new combinations of the genetic material, thus increasing genome repair and fitness. Additionally, HJ-mediated recombination can also result in unequal crossover and non-homologous recombination of the genetic makeup in the gametes or the daughter cells. Transposable elements (TEs) are repetitive DNA elements able to replicate in the genome and as we have previously reported can pair with HJs in such a way, that a significantly high proportion of HJs is associated with TEs.

Particular Microdeletion and Microduplication Syndromes (MMS) are rare recombinations, but as a whole (cumulatively) they represent a significant group of genetic abnormalities almost equal to aneuploidies. Some of them and in particular Di George Microdeletion can be found in frequencies second only to trisomy 21. Based on our database of MMS we found that almost all MMS span in length less than 5Mbs which is the cut-off point of resolution in standard cytogenetics. Furthermore, a significant percentage of them are in length less than 0.5Mbs and all together, short and long MMS, have a high probability to harbor TE-associated and non-TE associated HJs.

More importantly, gene proximity bioinformatic analysis revealed that a significantly high number of MMS associated HJs are proximal to regions of genes that control key developmental processes and transcription factors in humans.

Collectively, we propose that HJs and other recombination primers such as TEs that exist in regions spanning MMS hotspots underlie a possible mechanism for their occurrence during gametogenesis.