Thursday, 25th May, 2023, 12:00

Human inversions, genes, phenotypic traits and evolution

PRBB Computational Genomics Seminar. Chair: Mar Albà

During the last decades, there has been a growing interest to identify all genetic variants in humans and relate them to phenotypic traits and disease susceptibility. Most studies have focused in SNPs, but they have been able to explain just a small proportion of the genetic risk for complex diseases. The discovery of a large amount of structural variants (SVs), which affect bigger segments of DNA, suggested that they could account for part of this missing heritability. Nevertheless, the study of SVs has been hindered by the lack of a comprehensive catalogue of variants and the difficulty to identify them reliably in multiple individuals. Inversions are especially interesting because they affect recombination and could have negative consequences on fertility. However, they are often missed due to their balanced nature and the presence of highly-identical inverted repeats (IRs) at their breakpoints. As part of the INVFEST project, we have carried an exhaustive characterization of human inversion polymorphism at different levels. In particular, we have built the first non-redundant database of human inversions and characterized in detail more than 500 genome-wide predictions, eliminating many false ones. Thanks to the development of different methods to detect a wide-range of inversions, including those mediated by large IRs that typically escape most analysis, we have also generated the largest and most accurate population inversion dataset, totaling ~200 real inversion-like variants. This has shown that the majority of IR-mediated inversions have occurred recurrently multiple times and are not represented in typical genome-wide association studies (GWAS). Moreover, around half of the studied inversions have significant consequences on gene expression, epigenetic changes or disease association, emphasizing their important functional impact compared to other variants. Finally, several of the inversions show signals of positive or balancing selection. Therefore, this work contributes to a more complete understanding of human genetic variation and the role that inversions play in many organisms.

Zoom webinar: https://us02web.zoom.us/j/84212222322?pwd=VmVIdHo3czlFcVZUSDhscnQ0RzN5Zz09

Speaker: Mario Cáceres ICREA Research Professor, Research Programme on Biomedical Informatics (GRIB), IMIM (Hospital del Mar Medical Research Institute) and Institut de Biotecnologia i de Biomedicina (IBB), Universitat Autònoma de Barcelona (UAB).

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