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Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles.

ABSTRACT: 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 ? (PPAR?) 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.

SUBMITTER: Fairfax BP

PROVIDER: S-EPMC3437404 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles.

Fairfax Benjamin P BP Makino Seiko S Radhakrishnan Jayachandran J Plant Katharine K Leslie Stephen S Dilthey Alexander A Ellis Peter P Langford Cordelia C Vannberg Fredrik O FO Knight Julian C JC

Nature genetics 20120325 5

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 di ...[more]

PMID: 22446964

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Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles.

Publications

Genetics of gene expression in primary immune cells identifies cell type-specific master regulators and roles of HLA alleles.

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