英国伦敦国王学院Adrian C. Hayday课题组，利用高通量表型平台揭示了免疫变异广泛的遗传和结构基础。相关论文在线发表在2019年12月16日的《自然—免疫学》上。

研究人员通过开发与高通量遗传筛选兼容的高密度小鼠免疫表型平台，建立了遗传和结构对免疫变异影响的资源库（http://www.immunophenotype.org）。具体来说，通过对530个小鼠特异基因敲除的高通量表型分析，研究人员鉴定了140个“关键”单基因，这些基因大多数之前和免疫学并无关联。此外，人类对大多数这些关键基因功能丧失敏感。免疫表型平台还揭示了密集的相关网络，该网络不仅建立了免疫参数间的关联还与特定的生理特征联系在一起。这种联系限制了单个免疫参数的运动自由度，从而增强了基因调控的“免疫结构”，其完整性与免疫力有关。因此，该研究为理解和监测健康和疾病之间的免疫变异提供了扩展的遗传资源和结构视角。

附：英文原文

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

Author: Lucie Abeler-Drner, 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, Beln Morn, 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 C. Hayday

Issue&Volume: 2019-12-16

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.

DOI: 10.1038/s41590-019-0549-0

Source: https://www.nature.com/articles/s41590-019-0549-0