Assessing the digenic model in rare disorders using population sequencing data
| Autor: | Moreno-Ruiz, Nerea, Lao, Oscar, Arostegui, Juan Ignacio, Laayouni, Hafid, Casals, Ferran, Genomics England Research Consortium |
|---|---|
| Přispěvatelé: | Ministerio de Ciencia e Innovación (España), Agencia Estatal de Investigación (España), European Commission, Generalitat de Catalunya, Department of Health & Social Care (UK), National Institute for Health Research (UK), National Health Service (UK), Wellcome Trust, Medical Research Council (UK), Moreno-Ruiz, Nerea, Lao, Oscar, Arostegui, Juan Ignacio, Laayouni, Hafid, Casals, Ferran |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: | |
| Popis: | An important fraction of patients with rare disorders remains with no clear genetic diagnostic, even after whole-exome or whole-genome sequencing, posing a difficulty in giving adequate treatment and genetic counseling. The analysis of genomic data in rare disorders mostly considers the presence of single gene variants in coding regions that follow a concrete monogenic mode of inheritance. A digenic inheritance, with variants in two functionally-related genes in the same individual, is a plausible alternative that might explain the genetic basis of the disease in some cases. In this case, digenic disease combinations should be absent or underrepresented in healthy individuals. We develop a framework to evaluate the significance of digenic combinations and test its statistical power in different scenarios. We suggest that this approach will be relevant with the advent of new sequencing efforts including hundreds of thousands of samples. This study was funded by grants RTI2018-096824-B-C22 (FC), PID2021-125106OB-C32 (FC), RTI2018-096824-B-C21 (JIA) and PID2021-125106OB-C31 (JIA) funded by MCIN/ AEI /10.13039/501100011033/ and FEDER Una manera de hacer Europa; Direcció General de Recerca- Generalitat de Catalunya (2017SGR-702) (FC); and CERCA Programme/Generalitat de Catalunya (JIA). NMR was supported by grant 2021 FI_B_00296 from Agència de Gestió d’Ajuts Universitaris i de Recerca, Generalitat de Catalunya. This research was made possible through access to the data and findings generated by the 100,000 Genomes Project. The 100,000 Genomes Project is managed by Genomics England Limited (a wholly owned company of the Department of Health and Social Care). The 100,000 Genomes Project is funded by the National Institute for Health Research and NHS England. The Wellcome Trust, Cancer Research UK and the Medical Research Council have also funded research infrastructure. The 100,000 Genomes Project uses data provided by patients and collected by the National Health Service as part of their care and support. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|