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Exploring the RNA gap for improving diagnostic yield in primary immunodeficiencies

Exploring the RNA gap for improving diagnostic yield in primary immunodeficiencies
Exploring the RNA gap for improving diagnostic yield in primary immunodeficiencies
Challenges in diagnosing Primary Immunodeficiency are numerous and diverse, with current whole exome and whole genome sequencing approaches only able to reach a molecular diagnosis in 25-60% of cases. We assess these problems and discuss how RNA focused analysis has expanded and improved in recent years, and may now give be utilised to gain an unparalleled insight into cellular immunology. 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.
1664-8021
Lye, Jed
95f6689e-ec36-4c93-a63e-78ac67584ed2
Williams, Anthony
973ff46f-46f1-4d7c-b27d-0f53221e4c44
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
Lye, Jed
95f6689e-ec36-4c93-a63e-78ac67584ed2
Williams, Anthony
973ff46f-46f1-4d7c-b27d-0f53221e4c44
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91

Lye, Jed, Williams, Anthony and Baralle, Diana (2019) Exploring the RNA gap for improving diagnostic yield in primary immunodeficiencies. Frontiers in Genetics, 10, [1204]. (doi:10.3389/fgene.2019.01204).

Record type: Article

Abstract

Challenges in diagnosing Primary Immunodeficiency are numerous and diverse, with current whole exome and whole genome sequencing approaches only able to reach a molecular diagnosis in 25-60% of cases. We assess these problems and discuss how RNA focused analysis has expanded and improved in recent years, and may now give be utilised to gain an unparalleled insight into cellular immunology. 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.

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Lye Baralle and Williams Resub-clean - Accepted Manuscript
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More information

Accepted/In Press date: 31 October 2019
e-pub ahead of print date: 11 December 2019

Identifiers

Local EPrints ID: 435621
URI: http://eprints.soton.ac.uk/id/eprint/435621
ISSN: 1664-8021
PURE UUID: 21405ba6-7d76-40e7-be3a-9e1407f12577
ORCID for Diana Baralle: ORCID iD orcid.org/0000-0003-3217-4833

Catalogue record

Date deposited: 14 Nov 2019 17:30
Last modified: 26 Nov 2021 02:53

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Contributors

Author: Jed Lye
Author: Diana Baralle ORCID iD

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