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

By developing a high-density murine immunophenotyping platform compatible with highthroughput genetic screening, we have established profound contributions of genetics and structure to immune variation (www.immunophenotype.org). Specifically, highthroughput phenotyping of 530 unique mouse gene knock...

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Մատենագիտական մանրամասներ
Հիմնական հեղինակներ: Abeler-Dörner, L, Laing, A, Lorenc, A, Bull, K, Crockford, T, Cawthorne, E, Edmans, M, Cornall, R, Morón, B, Song-Zhao, G, Abeler, J, Powrie, F, Et al.
Ձևաչափ: Journal article
Հրապարակվել է: Springer Nature 2019
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author Abeler-Dörner, L
Laing, A
Lorenc, A
Bull, K
Crockford, T
Cawthorne, E
Edmans, M
Cornall, R
Morón, B
Song-Zhao, G
Abeler, J
Powrie, F
Et al.
author_facet Abeler-Dörner, L
Laing, A
Lorenc, A
Bull, K
Crockford, T
Cawthorne, E
Edmans, M
Cornall, R
Morón, B
Song-Zhao, G
Abeler, J
Powrie, F
Et al.
author_sort Abeler-Dörner, L
collection OXFORD
description By developing a high-density murine immunophenotyping platform compatible with highthroughput genetic screening, we have established profound contributions of genetics and structure to immune variation (www.immunophenotype.org). Specifically, highthroughput phenotyping of 530 unique mouse gene knockouts identified 140 monogenic “hits”, of which most had no previous immunological 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 one another and with specific physiologic traits. Such linkages limit freedom-of-movement for individual immune parameters, thereby imposing genetically regulated “immunological structures”, whose integrity was associated with immunocompetence. Hence, we provide an expanded genetic resource and structural perspective for understanding and monitoring immune variation in health and disease.
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spelling oxford-uuid:6b7b22c5-d43b-4422-bb82-c3fb5fc9c7f42022-03-26T19:04:25ZHigh-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variationJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:6b7b22c5-d43b-4422-bb82-c3fb5fc9c7f4Symplectic Elements at OxfordSpringer Nature2019Abeler-Dörner, LLaing, ALorenc, ABull, KCrockford, TCawthorne, EEdmans, MCornall, RMorón, BSong-Zhao, GAbeler, JPowrie, FEt al.By developing a high-density murine immunophenotyping platform compatible with highthroughput genetic screening, we have established profound contributions of genetics and structure to immune variation (www.immunophenotype.org). Specifically, highthroughput phenotyping of 530 unique mouse gene knockouts identified 140 monogenic “hits”, of which most had no previous immunological 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 one another and with specific physiologic traits. Such linkages limit freedom-of-movement for individual immune parameters, thereby imposing genetically regulated “immunological structures”, whose integrity was associated with immunocompetence. Hence, we provide an expanded genetic resource and structural perspective for understanding and monitoring immune variation in health and disease.
spellingShingle Abeler-Dörner, L
Laing, A
Lorenc, A
Bull, K
Crockford, T
Cawthorne, E
Edmans, M
Cornall, R
Morón, B
Song-Zhao, G
Abeler, J
Powrie, F
Et al.
High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation
title High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation
title_full High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation
title_fullStr High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation
title_full_unstemmed High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation
title_short High-throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation
title_sort high throughput phenotyping reveals expansive genetic and structural underpinnings of immune variation
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