Characterisation of the global transcriptional response to heat shock and the impact of individual genetic variation

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dc.contributor.authorHumburg, Peter
dc.contributor.authorMaugeri, Narelle
dc.contributor.authorLee, Wanseon
dc.contributor.authorMohr, Bert
dc.contributor.authorKnight, Julian C
dc.date.accessioned2021-10-08T07:04:06Z
dc.date.available2021-10-08T07:04:06Z
dc.date.issued2016
dc.description.abstractAbstract Background The heat shock transcriptional response is essential to effective cellular function under stress. This is a highly heritable trait but the nature and extent of inter-individual variation in heat shock response remains unresolved. Methods We determined global transcription profiles of the heat shock response for a panel of lymphoblastoid cell lines established from 60 founder individuals in the Yoruba HapMap population. We explore the observed differentially expressed gene sets following heat shock, establishing functional annotations, underlying networks and nodal genes involving heat shock factor 1 recruitment. We define a multivariate phenotype for the global transcriptional response to heat shock using partial least squares regression and map this quantitative trait to associated genetic variation in search of the major genomic modulators. Results A comprehensive dataset of differentially expressed genes following heat shock in humans is presented. We identify nodal genes downstream of heat shock factor 1 in this gene set, notably involving ubiquitin C and small ubiquitin-like modifiers together with transcription factors. We dissect a multivariate phenotype for the global heat shock response which reveals distinct clustering of individuals in terms of variance of the heat shock response and involves differential expression of genes involved in DNA replication and cell division in some individuals. We find evidence of genetic associations for this multivariate response phenotype that involves trans effects modulating expression of genes following heat shock, including HSF1 and UBQLN1. Conclusion This study defines gene expression following heat shock for a cohort of individuals, establishing insights into the biology of the heat shock response and hypotheses for how variation in this may be modulated by underlying genetic diversity.
dc.identifier.apacitationHumburg, P., Maugeri, N., Lee, W., Mohr, B., & Knight, J. C. (2016). Characterisation of the global transcriptional response to heat shock and the impact of individual genetic variation. <i>Genome Medicine</i>, 8(1), 174 - 177. http://hdl.handle.net/11427/34427en_ZA
dc.identifier.chicagocitationHumburg, Peter, Narelle Maugeri, Wanseon Lee, Bert Mohr, and Julian C Knight "Characterisation of the global transcriptional response to heat shock and the impact of individual genetic variation." <i>Genome Medicine</i> 8, 1. (2016): 174 - 177. http://hdl.handle.net/11427/34427en_ZA
dc.identifier.citationHumburg, P., Maugeri, N., Lee, W., Mohr, B. & Knight, J.C. 2016. Characterisation of the global transcriptional response to heat shock and the impact of individual genetic variation. <i>Genome Medicine.</i> 8(1):174 - 177. http://hdl.handle.net/11427/34427en_ZA
dc.identifier.issn1756-994X
dc.identifier.ris TY - Journal Article AU - Humburg, Peter AU - Maugeri, Narelle AU - Lee, Wanseon AU - Mohr, Bert AU - Knight, Julian C AB - Abstract Background The heat shock transcriptional response is essential to effective cellular function under stress. This is a highly heritable trait but the nature and extent of inter-individual variation in heat shock response remains unresolved. Methods We determined global transcription profiles of the heat shock response for a panel of lymphoblastoid cell lines established from 60 founder individuals in the Yoruba HapMap population. We explore the observed differentially expressed gene sets following heat shock, establishing functional annotations, underlying networks and nodal genes involving heat shock factor 1 recruitment. We define a multivariate phenotype for the global transcriptional response to heat shock using partial least squares regression and map this quantitative trait to associated genetic variation in search of the major genomic modulators. Results A comprehensive dataset of differentially expressed genes following heat shock in humans is presented. We identify nodal genes downstream of heat shock factor 1 in this gene set, notably involving ubiquitin C and small ubiquitin-like modifiers together with transcription factors. We dissect a multivariate phenotype for the global heat shock response which reveals distinct clustering of individuals in terms of variance of the heat shock response and involves differential expression of genes involved in DNA replication and cell division in some individuals. We find evidence of genetic associations for this multivariate response phenotype that involves trans effects modulating expression of genes following heat shock, including HSF1 and UBQLN1. Conclusion This study defines gene expression following heat shock for a cohort of individuals, establishing insights into the biology of the heat shock response and hypotheses for how variation in this may be modulated by underlying genetic diversity. DA - 2016 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - Genome Medicine LK - https://open.uct.ac.za PY - 2016 SM - 1756-994X T1 - Characterisation of the global transcriptional response to heat shock and the impact of individual genetic variation TI - Characterisation of the global transcriptional response to heat shock and the impact of individual genetic variation UR - http://hdl.handle.net/11427/34427 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/34427
dc.identifier.vancouvercitationHumburg P, Maugeri N, Lee W, Mohr B, Knight JC. Characterisation of the global transcriptional response to heat shock and the impact of individual genetic variation. Genome Medicine. 2016;8(1):174 - 177. http://hdl.handle.net/11427/34427.en_ZA
dc.language.isoeng
dc.publisher.departmentDepartment of Medicine
dc.publisher.facultyFaculty of Health Sciences
dc.sourceGenome Medicine
dc.source.journalissue1
dc.source.journalvolume8
dc.source.pagination174 - 177
dc.source.urihttps://dx.doi.org/10.1186/s13073-016-0345-5
dc.subject.otherB-Lymphocytes
dc.subject.otherCarrier Proteins
dc.subject.otherCell Cycle Proteins
dc.subject.otherCell Line
dc.subject.otherDNA Replication
dc.subject.otherDNA-Binding Proteins
dc.subject.otherFounder Effect
dc.subject.otherGene Ontology
dc.subject.otherGene Regulatory Networks
dc.subject.otherGenetic Variation
dc.subject.otherGenotype
dc.subject.otherHapMap Project
dc.subject.otherHeat Shock Transcription Factors
dc.subject.otherHeat-Shock Response
dc.subject.otherHumans
dc.subject.otherMolecular Sequence Annotation
dc.titleCharacterisation of the global transcriptional response to heat shock and the impact of individual genetic variation
dc.typeJournal Article
uct.type.publicationResearch
uct.type.resourceJournal Article
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