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DOI 10.1038/s41590-019-0549-0

Медицинская библиотека · Nature immunology · 2019

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

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

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПеревод в очереди

Аннотация

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.

Для цитирования: Abeler-Dörner Lucie, Laing Adam G, Lorenc Anna, Ushakov Dmitry S, Clare Simon, Speak Anneliese O, Duque-Correa Maria A, White Jacqueline K, Ramirez-Solis Ramiro, Saran Namita, Bull Katherine R, Morón Belén, Iwasaki Jua, Barton Philippa R, Caetano Susana, Hng Keng I, Cambridge Emma, Forman Simon, Crockford Tanya L, Griffiths Mark, Kane Leanne, Harcourt Katherine, Brandt Cordelia, Notley George, Babalola Kolawole O, Warren Jonathan, Mason Jeremy C, Meeniga Amrutha, Karp Natasha A, Melvin David, Cawthorne Eleanor, Weinrick Brian, Rahim Albina, Drissler Sibyl, Meskas Justin, Yue Alice, Lux Markus, Song-Zhao George X, Chan Anna, Ballesteros Reviriego Carmen, Abeler Johannes, Wilson Heather, Przemska-Kosicka Agnieszka, Edmans Matthew, Strevens Natasha, Pasztorek Markus, Meehan Terrence F, Powrie Fiona, Brinkman Ryan, Dougan Gordon, Jacobs William, Lloyd Clare M, Cornall Richard J, Maloy Kevin J, Grencis Richard K, Griffiths Gillian M, Adams David J, Hayday Adrian C. High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation.. Nature immunology. 2019. DOI: 10.1038/s41590-019-0549-0.

Предметные рубрики MeSH

AnimalsCitrobacterEnterobacteriaceae InfectionsFemaleGenetic VariationHigh-Throughput Screening AssaysHumansImmunophenotypingMaleMiceMice, Inbred C57BLMice, KnockoutModels, AnimalSalmonellaSalmonella Infections
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