Resultados de investigación

Folder: 1.Sequences - Sub-folder cDNA. Transcript Sequencing. Sub-folders: - ATM_19-22: 31 *.ab1 files of transcripts generated by variants introduced into minigene mgATM_19-22 - ATM_41-44: 15 *.ab1 files of transcripts generated by variants introduced into minigene mgATM_41-44 - ATM_55-63: 32 *.ab1 files of transcripts generated by variants introduced into minigene mgATM_55-63 - Sub-folder: Minigenes. Sequence files of wild type and mutant constructs. Sub-folders: - ATM_19-22: 17 *.ab1 files. - ATM_41-44: 11 *.ab1 files. - ATM_55-63: 25 *.ab1 files. • Folder: 2.Fragment_Analysis. Fluorescent Fragment Analysis of splicing assays. Sub-folders: - ATM_19-22: 53 *.fsa files of fluorescent fragment analysis of variant-spicing assays. - ATM_41-44: 30 *.fsa files of fluorescent fragment analysis of variant-spicing assays. - ATM_55-63: 72 *.fsa files of fluorescent fragment analysis of variant-spicing assays., This dataset contains fragment analysis and sequencing files of the impact on splicing of splice-site variants in 17 exons of the breast cancer susceptibility gene ATM. Splicing dysregulation is a well-established mechanism of pathogenicity for variants in disease susceptibility genes. Pathogenic germline variants in ATM are associated with a 20–30% lifetime risk of breast cancer. We aimed to carry out splicing analysis of ATM splice-site variants detected in subjects of the large-scale sequencing project BRIDGES (https://cordis.europa.eu/project/id/634935) by minigene assays. To this end, we bioinformatically selected 47 splice-site variants in 17 exons that were genetically engineered into three minigenes and assayed in MCF-7 cells. Aberrant splicing was observed in 38 variants. Of these, 29 showed no or negligible minigene full-length (mgFL) transcript expression, including eight exonic variants (7 missense and one nonsense). All minigene read-outs from variants were interpreted according to the ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology)-based specifications for the ATM gene., EAV-S lab has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 634935, and from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (PI23/00047) co-funded by FEDER from Regional Development European Funds (European Union)., Peer reviewed