Overview of Research on Germline Genetic Variation in Immune Genes and Cancer Outcomes

2022 ◽  
pp. cebp.0583.2021
Author(s):  
Brittany N Chao ◽  
Danielle M Carrick ◽  
Kelly K Filipski ◽  
Stefanie A Nelson
2020 ◽  
Vol 295 (10) ◽  
pp. 3228-3238 ◽  
Author(s):  
Joseph K. Rathkey ◽  
Tsan S. Xiao ◽  
Derek W. Abbott

Exomic studies have demonstrated that innate immune genes exhibit an even higher degree of variation than the majority of other gene families. However, the phenotypic implications of this genetic variation are not well understood, with effects ranging from hypomorphic to silent to hyperfunctioning. In this work, we study the functional consequences of this variation by investigating polymorphisms in gasdermin D, the key pyroptotic effector protein. We find that, although SNPs affecting potential posttranslational modifications did not affect gasdermin D function or pyroptosis, polymorphisms disrupting sites predicted to be structurally important dramatically alter gasdermin D function. The manner in which these polymorphisms alter function varies from conserving normal pyroptotic function to inhibiting caspase cleavage to disrupting oligomerization and pore formation. Further, downstream of inflammasome activation, polymorphisms that cause loss of gasdermin D function convert inflammatory pyroptotic cell death into immunologically silent apoptotic cell death. These findings suggest that human genetic variation can alter mechanisms of cell death in inflammation.


2010 ◽  
Vol 55 (1) ◽  
pp. 87-94 ◽  
Author(s):  
Theo S Plantinga ◽  
Omar J M Hamza ◽  
Janet A Willment ◽  
Bart Ferwerda ◽  
Nicole M D van de Geer ◽  
...  

2015 ◽  
Vol 26 ◽  
pp. ix148 ◽  
Author(s):  
H. Liu ◽  
Y.-X. Li ◽  
Y.-F. Wen ◽  
M.-Y. Zhang ◽  
Q.-Y. Chen ◽  
...  

2019 ◽  
Author(s):  
Wen-Hao Tan ◽  
Andrew J. Mongue ◽  
Jacobus C. de Roode ◽  
Nicole M. Gerardo ◽  
James R. Walters

ABSTRACTImmune genes presumably rapidly evolve as pathogens exert strong selection pressures on host defense, but the evolution of immune genes is also constrained by trade-offs with other biological functions and shaped by the environmental context. Thus, immune genes may exhibit complex evolutionary patterns, particularly when organisms disperse to or live in variable environments. We examined the evolutionary patterns of the full set of known canonical immune genes within and among populations of monarch butterflies (Danaus plexippus), and relative to a closely related species (D. gilippus). Monarchs represent a system with a known evolutionary history, in which North American monarchs dispersed to form novel populations across the world, providing an opportunity to explore the evolution of immunity in the light of population expansion into novel environments. By analyzing a whole-genome resequencing dataset across populations, we found that immune genes as a whole do not exhibit consistent patterns of selection, differentiation, or genetic variation, but that patterns are specific to functional classes. Species comparisons between D. plexippus and D. gilippus and analyses of monarch populations both revealed consistently low levels of genetic variation in signaling genes, suggesting conservation of these genes over evolutionary time. Modulation genes showed the opposite pattern, with signatures of relaxed selection across populations. In contrast, recognition and effector genes exhibited less consistent patterns. When focusing on genes with exceptionally strong signatures of selection or differentiation, we also found population-specific patterns, consistent with the hypothesis that monarch populations do not face uniform selection pressures with respect to immune function.


2015 ◽  
Vol 5 (3) ◽  
pp. 329-339 ◽  
Author(s):  
Susan M Rottschaefer ◽  
Jacob E Crawford ◽  
Michelle M Riehle ◽  
Wamdaogo M Guelbeogo ◽  
Awa Gneme ◽  
...  

Abstract Natural selection is expected to drive adaptive evolution in genes involved in host–pathogen interactions. In this study, we use molecular population genetic analyses to understand how natural selection operates on the immune system of Anopheles coluzzii (formerly A. gambiae “M form”). We analyzed patterns of intraspecific and interspecific genetic variation in 20 immune-related genes and 17 nonimmune genes from a wild population of A. coluzzii and asked if patterns of genetic variation in the immune genes are consistent with pathogen-driven selection shaping the evolution of defense. We found evidence of a balanced polymorphism in CTLMA2, which encodes a C-type lectin involved in regulation of the melanization response. The two CTLMA2 haplotypes, which are distinguished by fixed amino acid differences near the predicted peptide cleavage site, are also segregating in the sister species A. gambiae (“S form”) and A. arabiensis. Comparison of the two haplotypes between species indicates that they were not shared among the species through introgression, but rather that they arose before the species divergence and have been adaptively maintained as a balanced polymorphism in all three species. We additionally found that STAT-B, a retroduplicate of STAT-A, shows strong evidence of adaptive evolution that is consistent with neofunctionalization after duplication. In contrast to the striking patterns of adaptive evolution observed in these Anopheles-specific immune genes, we found no evidence of adaptive evolution in the Toll and Imd innate immune pathways that are orthologously conserved throughout insects. Genes encoding the Imd pathway exhibit high rates of amino acid divergence between Anopheles species but also display elevated amino acid diversity that is consistent with relaxed purifying selection. These results indicate that adaptive coevolution between A. coluzzii and its pathogens is more likely to involve novel or lineage-specific molecular mechanisms than the canonical humoral immune pathways.


2013 ◽  
Vol 22 (1) ◽  
pp. 77-82 ◽  
Author(s):  
Qian Deng ◽  
Tongzhang Zheng ◽  
Qing Lan ◽  
Yajia Lan ◽  
Theodore Holford ◽  
...  

2011 ◽  
Vol 185 (4S) ◽  
Author(s):  
Robert Hamilton ◽  
Joseph Vijai ◽  
David Gallagher ◽  
Caroline Savage ◽  
Jasmine Bhatia ◽  
...  

2007 ◽  
Vol 177 (4S) ◽  
pp. 95-95
Author(s):  
Atreya Dash ◽  
Peng Lee ◽  
Qin Zhou ◽  
Aaron D. Berger ◽  
Jerome Jean-Gilles ◽  
...  

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