Study of transcriptional effects in Cis at the IFIH1 locus.

PloS One
Hana ZoukConstantin Polychronakos

Abstract

The Thr allele at the non-synonymous single-nucleotide polymorphism (nsSNP) Thr946Ala in the IFIH1 gene confers risk for Type 1 diabetes (T1D). The SNP is embedded in a 236 kb linkage disequilibrium (LD) block that includes four genes: IFIH1, GCA, FAP and KCNH7. The absence of common nsSNPs in the other genes makes the IFIH1 SNP the strongest functional candidate, but it could be merely a marker of association, due to LD with a variant regulating expression levels of IFIH1 or neighboring genes. We investigated the effect of the T1D-associated variation on mRNA transcript expression of these genes. Heterozygous mRNA from lymphoblastoid cell lines (LCLs), pancreas and thymus was examined by allelic expression imbalance, to detect effects in cis on mRNA expression. Using single-nucleotide primer extension, we found no difference between mRNA transcripts in 9 LCLs, 6 pancreas and 13 thymus samples, suggesting that GCA and FAP are not involved. On the other hand, KCNH7 was not expressed at a detectable level in all tissues examined. Moreover, the association of the Thr946Ala SNP with T1D is not due to modulation of IFIH1 expression in organs involved in the disease, pointing to the IFIH1 nsSNP as the causal variant. The mechanism of...Continue Reading

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Citations

Jan 15, 2014·International Journal of Clinical Rheumatology·Yogita Ghodke-Puranik, Timothy B Niewold
Sep 17, 2010·PloS One·Kate DownesJohn A Todd
Oct 19, 2011·Nature Reviews. Genetics·Constantin Polychronakos, Quan Li
Oct 15, 2013·Autoimmunity·Hana ZoukConstantin Polychronakos
Jun 27, 2014·Scandinavian Journal of Immunology·M PanarinaR Uibo
Aug 19, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Franziska S HoffmannSimon Rothenfusser
Sep 20, 2015·Current Diabetes Reports·Benjamin M LooneyMichael J Clare-Salzler
Mar 14, 2014·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·L PangZ Duan
Jul 22, 2014·Journal of Diabetes·Alejandra RodríguezNicolás Pineda Trujillo
Dec 18, 2014·Diabetes Research and Clinical Practice·Magdalena ZurawekJerzy Nowak
Jun 28, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Talin RobinsonTimothy B Niewold

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Methods Mentioned

BETA
transfection
PCR
electrophoresis

Software Mentioned

GeneScan
Genescan Analysis

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