Format

Send to

Choose Destination
Nat Immunol. 2020 Jan;21(1):86-100. doi: 10.1038/s41590-019-0549-0. Epub 2019 Dec 16.

High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation.

Author information

1
Department of Immunobiology, King's College London, London, UK.
2
The Francis Crick Institute, London, UK.
3
Wellcome Sanger Institute, Hinxton, UK.
4
MRC Human Immunology Unit, University of Oxford, Oxford, UK.
5
Sir William Dunn School of Pathology, University of Oxford, Oxford, UK.
6
National Heart and Lung Institute, Imperial College London, London, UK.
7
Cambridge Institute of Medical Research, University of Cambridge, Cambridge, UK.
8
Lydia Becker Institute of Immunology and Inflammation, Wellcome Trust Centre for Cell Matrix Research, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
9
European Bioinformatics Institute, European Molecular Biology Laboratory, Hinxton, UK.
10
Data Sciences & Quantitative Biology, Discovery Sciences, R&D Biopharmaceuticals, AstraZeneca, Cambridge, UK.
11
Department of Microbiology and Immunology, Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
12
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada.
13
Department of Economics, University of Oxford, Oxford, UK.
14
Department of Biomedical Science, University of Applied Sciences FH Campus Wien, Vienna, Austria.
15
The Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
16
Department of Bioinformatics, University of British Columbia, Vancouver, BC, Canada.
17
Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, UK.
18
Department of Immunobiology, King's College London, London, UK. adrian.hayday@kcl.ac.uk.
19
The Francis Crick Institute, London, UK. adrian.hayday@kcl.ac.uk.

Abstract

By developing a high-density murine immunophenotyping platform compatible with high-throughput genetic screening, we have established profound contributions of genetics and structure to immune variation (http://www.immunophenotype.org). Specifically, high-throughput phenotyping of 530 unique mouse gene knockouts identified 140 monogenic 'hits', of which most had no previous immunologic association. Furthermore, hits were collectively enriched in genes for which humans show poor tolerance to loss of function. The immunophenotyping platform also exposed dense correlation networks linking immune parameters with each other and with specific physiologic traits. Such linkages limit freedom of movement for individual immune parameters, thereby imposing genetically regulated 'immunologic structures', the integrity of which was associated with immunocompetence. Hence, we provide an expanded genetic resource and structural perspective for understanding and monitoring immune variation in health and disease.

PMID:
31844327
DOI:
10.1038/s41590-019-0549-0

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center