PT  - JOURNAL ARTICLE
AU  - Lucie Abeler-Dörner
AU  - Adam G. Laing
AU  - Anna Lorenc
AU  - Dmitry S. Ushakov
AU  - Simon Clare
AU  - Anneliese Speak
AU  - Maria Duque
AU  - Jacqui K. White
AU  - Ramiro Ramirez-Solis
AU  - Namita Saran
AU  - Katherine R. Bull
AU  - Belén Morón
AU  - Jua Iwasaki
AU  - Philippa R. Barton
AU  - Susana Caetano
AU  - Keng I. Hng
AU  - Emma Cambridge
AU  - Simon Forman
AU  - Tanya L. Crockford
AU  - Mark Griffiths
AU  - Leanne Kane
AU  - Katherine Harcourt
AU  - Cordelia Brandt
AU  - George Notley
AU  - Kolawole O. Babalola
AU  - Jonathan Warren
AU  - Jeremy C. Mason
AU  - Amrutha Meeniga
AU  - Natasha A. Karp
AU  - David Melvin
AU  - Eleanor Cawthorne
AU  - Brian Weinrick
AU  - Albina Rahim
AU  - Sibyl Drissler
AU  - Justin Meskas
AU  - Alice Yue
AU  - Markus Lux
AU  - George Song-Zhao
AU  - Anna Chan
AU  - Carmen Ballesteros Reviriego
AU  - Johannes Abeler
AU  - Heather Wilson
AU  - Agnieszka Przemska-Kosicka
AU  - Matthew Edmans
AU  - Natasha Strevens
AU  - Markus Pasztorek
AU  - Terrence F. Meehan
AU  - Fiona Powrie
AU  - Ryan Brinkman
AU  - Gordon Dougan
AU  - William Jacobs, Jr
AU  - Clare Lloyd
AU  - Richard J. Cornall
AU  - Kevin Maloy
AU  - Richard Grencis
AU  - Gillian M. Griffiths
AU  - David Adams
AU  - Adrian C. Hayday
TI  - High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation
AID  - 10.1101/688010
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 688010
4099  - http://biorxiv.org/content/early/2019/07/10/688010.short
4100  - http://biorxiv.org/content/early/2019/07/10/688010.full
AB  - 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. Specifically, high-throughput phenotyping of 530 knockout mouse lines identified 140 monogenic “hits” (>25%), most of which had never hitherto been implicated in immunology. Furthermore, they were conspicuously 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 one another and with specific physiologic traits. By limiting the freedom of individual immune parameters, such linkages impose genetically regulated “immunological structures”, whose integrity was found to be associated with immunocompetence. Hence, our findings provide an expanded genetic resource and structural perspective for understanding and monitoring immune variation in health and disease.