Journal article

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

Pauline A van Schouwenburg, Emma E Davenport, Anne-Kathrin Kienzler, Ishita Marwah, Benjamin Wright, Mary Lucas, Tomas Malinauskas, Hilary C Martin, Helen E Lockstone, Jean-Baptiste Cazier, Helen M Chapel, Julian C Knight, Smita Y Patel

CLINICAL IMMUNOLOGY | ACADEMIC PRESS INC ELSEVIER SCIENCE | Published : 2015

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 signalli..

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University of Melbourne Researchers

Grants

Awarded by Long-term Fellowship from the Human Frontier Science Program


Awarded by European Research Council under the European Union's Seventh Framework Programme


Awarded by Wellcome Trust


Awarded by Cancer Research UK


Awarded by Medical Research Council


Funding Acknowledgements

TM is funded by a Long-term Fellowship from the Human Frontier Science Program grant LT000021/2014-L. JCK is supported by the European Research Council under the European Union's Seventh Framework Programme (FP7/2007-2013)/ERC Grant agreement no. 281824, and the NIHR Oxford Biomedical Research Centre. The Wellcome Trust grant 090532/Z/09/Z supports the core facilities Wellcome Trust Centre for Human Genetics including the High-throughput Genomics Group. SYP is funded by the NIHR Oxford Biomedical Research Centre and the Jeffrey Model Foundation.