Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency disorders.
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Common Variable Immunodeficiency Disorders (CVIDs) are the most prevalent cause of primary antibody failure. CVIDs are highly variable and a genetic causes have been identified in <5% of patients. Here, we performed whole genome sequencing (WGS) of 34 CVID patients (94% sporadic) and combined them with transcriptomic profiling (RNA-sequencing of B cells) from three patients and three healthy controls. We identified variants in CVID disease genes TNFRSF13B, TNFRSF13C, LRBA and NLRP12 and enrichment of variants in known and novel disease pathways. The pathways identified include B-cell receptor signalling, non-homologous end-joining, regulation of apoptosis, T cell regulation and ICOS signalling. Our data confirm the polygenic nature of CVID and suggest individual-specific aetiologies in many cases. Together our data show that WGS in combination with RNA-sequencing allows for a better understanding of CVIDs and the identification of novel disease associated pathways.
Date Issued
2015-06-26
Date Acceptance
2015-05-20
Citation
Clinical Immunology, 2015, 160 (2), pp.301-314
ISSN
1521-7035
Publisher
Elsevier
Start Page
301
End Page
314
Journal / Book Title
Clinical Immunology
Volume
160
Issue
2
Copyright Statement
© 2015 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/).
(http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
PII: S1521-6616(15)00214-4
Subjects
B-cell
Common variable immunodeficiency
Polygenic
Transcriptome
Whole genome sequencing
Publication Status
Published