Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency

van Schouwenburg, Pauline A., Davenport, Emma E., Kienzler, Anne-Kathrin, Marwah, Ishita, Wright, Benjamin, Lucas, Mary, Malinauskas, Tomas, Martin, Hilary C., Lockstone, Helen E., Cazier, Jean-Baptiste, Chapel, Helen M., Knight, Julian C., Patel, Smita Y. (June 2015) Application of whole genome and RNA sequencing to investigate the genomic landscape of common variable immunodeficiency. Clinical Immunology, 160 (2). pp. 301-314. ISSN 1521-6616

DOI: 10.1016/j.clim.2015.05.020


Common Variable Immunodeficiency Disorders (CVIDs) are the most prevalent cause of primary antibody failure. CVIDs are a highly variable disease and a genetic cause has 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. By using an extensive analysis strategy we found 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 a polygenic nature of CVID and suggest individual-specific aetiologies in many cases. Together out data show that WGS in combination with RNA-sequencing allows for a better understanding of CVIDs and the identification of novel disease associated pathways.

Item Type: Paper
Uncontrolled Keywords: Common variable immunodeficiency Whole genome sequencing Transcriptome Polygenic B-cell
Subjects: bioinformatics > genomics and proteomics
Investigative techniques and equipment > assays > RNA-seq
Investigative techniques and equipment > assays > whole genome sequencing
CSHL Authors:
Communities: CSHL labs > Furukawa lab
Depositing User: Matt Covey
Date: 26 June 2015
Date Deposited: 01 Jul 2015 19:36
Last Modified: 27 Oct 2015 19:20
PMCID: PMC4601528
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