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

Oleh:

Fairfax, Benjamin P ; Makino, Seiko ; Radhakrishnan, Jayachandran

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Nature Genetics vol. 44 no. 05 (May 2012), page 502–510.

Ketersediaan

Perpustakaan FK Nomor Panggil: N12.K.2012.01 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

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.

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