Periodic Reporting for period 1 - IN2DIAG (Application of genomic inversions as diagnostic markers in precision medicine)
Berichtszeitraum: 2017-07-01 bis 2018-12-31
Despite the expectations of genome variation studies, only a small proportion of the genetic risk of common and complex diseases has been identified so far. Nevertheless, not all types of genomic variants have been studied to the same detail and most of the work has focused on single nucleotide polymorphisms (SNPs) and copy number variants (CNVs). Inversions, on the other hand, affect a large fraction of the human genome and are implicated in phenotypic differences in diverse organisms. However, their unique characteristics make inversion detection especially challenging and their effects have been largely missed by current genome-wide association studies. The aim of this project is to take advantage of the development of a novel high-throughput method for genotyping multiple human inversions in hundreds of individuals to bring the technology closer to the society as a way to determine the contribution of inversions to human diseases. In particular, a big effort has been devoted to optimize the available method through the development of new inversion assays (up to 37 inversions), increasing the accuracy of the genotypes, and decreasing the costs of the whole process. Moreover, we have carried out a preliminary analysis of inversion frequency in ~100 controls and cases of 8 diseases, including type 2 diabetes, lipid related disorders, essential hypertension, rheumatoid arthritis, asthma, Psoriasis, Alzheimer and Parkinson. Finally, through extensive contacts with different companies and potential investors, other dissemination activities and the creation of a new webpage that aims to be a central hub for inversion information, the project has contributed to raise awareness of the importance of inversions. Overall, although inversion genotyping remains a challenging process, this work represents a significant step forward in bringing the study of these elusive variants to the market, making possible a more complete analysis of the genome and helping to fulfill precision medicine promises.