Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles
Trans-acting genetic variants have a substantial, albeit poorly characterized, role in the heritable determination of gene expression. Using paired purified primary monocytes and B cells, we identify new predominantly cell type-specific cis and trans expression quantitative trait loci (eQTLs), inclu...
| Egile Nagusiak: | , , , , , , , , , |
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| Formatua: | Journal article |
| Hizkuntza: | English |
| Argitaratua: |
2012
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| _version_ | 1826276859925495808 |
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| author | Fairfax, B Makino, S Radhakrishnan, J Plant, K Leslie, S Dilthey, A Ellis, P Langford, C Vannberg, F Knight, J |
| author_facet | Fairfax, B Makino, S Radhakrishnan, J Plant, K Leslie, S Dilthey, A Ellis, P Langford, C Vannberg, F Knight, J |
| author_sort | Fairfax, B |
| collection | OXFORD |
| description | Trans-acting genetic variants have a substantial, albeit poorly characterized, role in the heritable determination of gene expression. Using paired purified primary monocytes and B cells, we identify new predominantly cell type-specific cis and trans expression quantitative trait loci (eQTLs), including multi-locus trans associations to LYZ and KLF4 in monocytes and B cells, respectively. Additionally, we observe a B cell-specific trans association of rs11171739 at 12q13.2, a known autoimmune disease locus, with IP6K2 (P = 5.8 × 10 -15), PRIC285 (P = 3.0 × 10 -10) and an upstream region of CDKN1A (P = 2 × 10 -52), suggesting roles for cell cycle regulation and peroxisome proliferator-activated receptor γ (PPARγ) signaling in autoimmune pathogenesis. We also find that specific human leukocyte antigen (HLA) alleles form trans associations with the expression of AOAH and ARHGAP24 in monocytes but not in B cells. In summary, we show that mapping gene expression in defined primary cell populations identifies new cell type-specific trans-regulated networks and provides insights into the genetic basis of disease susceptibility. © 2012 Nature America, Inc. All rights reserved. |
| first_indexed | 2024-03-06T23:20:11Z |
| format | Journal article |
| id | oxford-uuid:687627ef-b0fa-46a6-bd9f-4a17e7a849c6 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:20:11Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:687627ef-b0fa-46a6-bd9f-4a17e7a849c62022-03-26T18:45:02ZGenetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA allelesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:687627ef-b0fa-46a6-bd9f-4a17e7a849c6EnglishSymplectic Elements at Oxford2012Fairfax, BMakino, SRadhakrishnan, JPlant, KLeslie, SDilthey, AEllis, PLangford, CVannberg, FKnight, JTrans-acting genetic variants have a substantial, albeit poorly characterized, role in the heritable determination of gene expression. Using paired purified primary monocytes and B cells, we identify new predominantly cell type-specific cis and trans expression quantitative trait loci (eQTLs), including multi-locus trans associations to LYZ and KLF4 in monocytes and B cells, respectively. Additionally, we observe a B cell-specific trans association of rs11171739 at 12q13.2, a known autoimmune disease locus, with IP6K2 (P = 5.8 × 10 -15), PRIC285 (P = 3.0 × 10 -10) and an upstream region of CDKN1A (P = 2 × 10 -52), suggesting roles for cell cycle regulation and peroxisome proliferator-activated receptor γ (PPARγ) signaling in autoimmune pathogenesis. We also find that specific human leukocyte antigen (HLA) alleles form trans associations with the expression of AOAH and ARHGAP24 in monocytes but not in B cells. In summary, we show that mapping gene expression in defined primary cell populations identifies new cell type-specific trans-regulated networks and provides insights into the genetic basis of disease susceptibility. © 2012 Nature America, Inc. All rights reserved. |
| spellingShingle | Fairfax, B Makino, S Radhakrishnan, J Plant, K Leslie, S Dilthey, A Ellis, P Langford, C Vannberg, F Knight, J Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles |
| title | Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles |
| title_full | Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles |
| title_fullStr | Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles |
| title_full_unstemmed | Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles |
| title_short | Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles |
| title_sort | genetics of gene expression in primary immune cells identifies cell type specific master regulators and roles of hla alleles |
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