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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Genet. | doi: 10.3389/fgene.2019.01204

Exploring the RNA gap for improving diagnostic yield in Primary Immunodeficiencies

 Jed Lye1, Tony Williams1 and  Diana Baralle1*
  • 1University of Southampton, United Kingdom

Challenges in diagnosing Primary Immunodeficiency are numerous and diverse, currently whole exome sequencing and whole genome sequencing is only able to produce reliable diagnosis in 25-60% of cases. We assess these problems and demonstrate how RNA investigation technology and literature has experienced great leaps forward in recent years, and can now give unparalleled insight into the elegant inner workings of the cell. We review how investigation into RNA biology can give information regarding the differential expression, mono-allelic expression, and alternative splicing – which have important roles in immune regulation and function. We show how this information can inform bioinformatic analysis pipelines and aid in the variant filtering process, expediting the identification of causal variants – especially those affecting splicing, and enhance overall diagnostic ability. We also demonstrate the challenges, which remain in the design of this type of investigation, regarding technological limitation and biological considerations and suggest potential directions for the clinical applications.

Keywords: Primary immunodeficiencies (PIDs), RNA, RNAseq, Clinical diagnostics, RNAseq analysis

Received: 02 Sep 2019; Accepted: 31 Oct 2019.

Copyright: © 2019 Lye, Williams and Baralle. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Diana Baralle, University of Southampton, Southampton, United Kingdom,