Genomic disorders are human diseases caused by DNA reorganizations leading to a gain, loss or alteration of dosage-sensitive genes. Usually, these disorders involve unstable chromosome regions, originate during gametogenesis and are due to non-faithful meiotic recombination processes (Non-Allelic Homologous Recombination – NAHR). Unstable chromosome regions involved in genome disorders are usually flanked by several blocks of Low Copy Repeats (LCRs). LCRs containing highly similar duplicated sequences and they play an important role in NAHR as their greatly homology promote these events.
One of these events, loss of genetic material, causes 22q11.2 deletion syndrome (22q11.2DS), also known as DiGeorge/Velocardiofacial syndrome (DG/VCFS). It is one of the most frequent human genomic disorder occurring in 1/4000 live births, and it is caused by deletions of genes from the region q11.2 of chromosome 22, which contains eight LCRs. It has been reported that in 90% of the affected individuals the deletions have arisen the novo. We have focused our investigation to analyse genetic factors that could influence NAHR events and allow to identify individuals at risk for fathering children with reorganizations involving this region. Our final goal is to extrapolate our findings to other chromosomal entities with similar genomic architectures that are implicated in other genomic disorders.