High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variationMore about Open Access at the Crick
Authors listLucie Abeler-Dörner Adam G Laing Anna Lorenc Dmitry S Ushakov Simon Clare Anneliese O Speak Maria A Duque-Correa Jacqueline K White Ramiro Ramirez-Solis Namita Saran Katherine R Bull Belén Morón Jua Iwasaki Philippa R Barton Susana Caetano Keng I Hng Emma Cambridge Simon Forman Tanya L Crockford Mark Griffiths Leanne Kane Katherine Harcourt Cordelia Brandt George Notley Kolawole O Babalola Jonathan Warren Jeremy C Mason Amrutha Meeniga Natasha A Karp David Melvin Eleanor Cawthorne Brian Weinrick Albina Rahim Sibyl Drissler Justin Meskas Alice Yue Markus Lux George X Song-Zhao Anna Chan Carmen Ballesteros Reviriego Johannes Abeler Heather Wilson Agnieszka Przemska-Kosicka Matthew Edmans Natasha Strevens Markus Pasztorek Terrence F Meehan Fiona Powrie Ryan Brinkman Gordon Dougan William Jacobs Clare M Lloyd Richard J Cornall Kevin J Maloy Richard K Grencis Gillian M Griffiths David J Adams Adrian Hayday
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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.
Journal Nature Immunology
Issue number 1