G7c , a novel gene in the mouse and human major histocompatibility complex class III region, possibly controlling lung tumor susceptibility

Snoek, Michiel; Albertella, Mark R.; Kooij, Marinus van Marwijk; Wixon, Jo; Vugt, H. van; Groot, K. de; Campbell, R. Duncan

doi:10.1007/s002510050634

Cited by 13 publications

(8 citation statements)

References 23 publications

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“…We also reported supportive data for a candidate class III susceptibility gene located within a 120 Kb interval flanked by the proximal VARS and distal GPANK1 genes, and spanning members of the leucocyte antigen-6 ( LY6 ) gene superfamily and other class III genes including casein kinase 2B ( CSNK2B ) implicated in endometrial and esophageal carcinoma and colorectal cancer (17–19), von Willebrand factor A domain containing 7 ( VWA7 ) in lung cancer susceptibility (20) and chloride intracellular channel 1 ( CLIC1 ) in gliomas (21), gastric (22) and hepatic cancer (23). …”

Section: Discussionmentioning

confidence: 74%

SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi’s sarcoma

et al. 2014

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The major histocompatibility complex (MHC) region on chromosome 6p21.3 is suspected to host susceptibility loci for HIV-related Kaposi’s sarcoma (HIV-KS). A nested case-control study in the Multicenter AIDS Cohort Study was designed to conduct fine genetic association mapping across central MHC. Individuals co-infected with HIV-1 and HHV-8 who later developed KS were defined as cases (n=354) and were matched 1:1 with co-infected KS-free controls. We report data for new independent MHC class II and III susceptibility loci. In particular, class II HLA-DMB emerged as a strong candidate, with the intronic variant rs6902982 A>G associated with a 4-fold increase of risk (OR= 4.09; 95% CI: 1.90–8.80; p= 0.0003). A striking multiplicative effect on the estimated risk was associated with further carriage of two non-synonymous variants, rs1800453 A>G (Asp697Gly) and rs4148880 A>G (Ile393Val), in the linked TAP1 gene (OR=10.5; 95% CI: 2.54–43.6; p=0.0012). The class III susceptibility variant is moderately associated with HIV-KS and lies within a 120 Kb-long haplotype (OR=1.52; 95% CI: 1.01–2.28; p=0.047) formed by rs7029 A>G (GPANK1 3’UTR), rs1065356 G>A (LY6G6C), rs3749953 A>G (MSH5-SAPCD1 readthrough) and rs707926 G>A (VARS). Our data suggest that antigen processing by MHC class II molecules is a target pathway in the pathogenesis of HIV-KS.

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Section: Discussionmentioning

confidence: 74%

SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi’s sarcoma

et al. 2014

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“…Fignl1 had already been linked to the cell cycle, but up to now with discrepant effects [29, 30]. The last gene called, G7e , also known as D17H6S56E-5 , was essentially uncharacterised, although located in a tumour susceptibility locus [31, 32]. Expression of Fignl1 and G7e was strongly correlated with essential cell cycle genes in public human and mouse microarray databases, analysed via Multi Experiment Matrix: MEM [33] (ESM Tables 4 and 5).…”

Section: Resultsmentioning

confidence: 99%

“…Remarkably, the rodent-specific G7e (ESM Fig. 7b), located in the major histocompatibility complex class III, is homologous to the envelope protein of murine leukaemia virus and maps in a lung tumour susceptibility locus [31, 32]. The intriguing possibility therefore is that a virally transduced gene stably integrated in the mouse genome is expressed in a regulated manner in order to support cell division, but also controls susceptibility to tumour development.…”

Section: Discussionmentioning

confidence: 99%

mRNA expression analysis of cell cycle genes in islets of pregnant mice

et al. 2010

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Aims/hypothesisPregnancy requires an increase in the functional beta cell mass to match metabolic needs for insulin. To understand this adaptation at the molecular level, we undertook a time course analysis of mRNA expression in mice.MethodsTotal RNA extracted from C57Bl6/J mouse islets every 3 days during pregnancy was hybridised on commercially available expression arrays. Gene network analysis was performed and changes in functional clusters over time visualised. The function of putative novel cell cycle genes was assessed via silencing in replicating mouse insulinoma 6 (MIN6) cells.ResultsGene network analysis identified a large gene cluster associated with cell cycle control (67 genes, all upregulated by ≥1.5-fold, p < 0.001). The number of upregulated cell cycle genes and the mRNA expression levels of individual genes peaked at pregnancy day (P)9.5. Filtering of poorly annotated genes with enhanced expression in islets at P9.5, and in MIN6 cells and thymus resulted in further studies with G7e (also known as D17H6S56E-5) and Fignl1. Gene knock-down experiments in MIN6 cells suggested that these genes are indeed involved in adequate cell cycle accomplishment.Conclusions/interpretationA sharp peak of cell cycle-related mRNA expression in islets occurs around P9.5, after which beta cell replication is increased. As illustrated by the identification of G7e and Fignl1 in islets of pregnant mice, further study of this distinct transcriptional peak should help to unravel the complex process of beta cell replication.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-010-1912-8) contains supplementary material, which is available to authorised users.

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“…, 1996 ). Snoek et al . (2000) have shown that the amino acid sequence of G7c is 28% identical to the Caenorhabditis elegans hemicentin precursor protein.…”

Section: Discussionmentioning

confidence: 99%

“…B10.A(1R) and B10.A(2R) mice have been used to map the gene responsible for corticoid-induced cleft palate (Gasser et al, 1988), vitamin A-enhanced cleft palate (Tyan & Tyan, 1993) and eye defects (microphthalmia and anophthalmia) (Tyan, 1992), resistance to alveolar lung tumours (Fijneman et al, 1995) and orchitis (Snoek et al, 1993) to the same 27 kb region. It encompasses G7a (Bat6, Vars2; valyl tRNA synthetase; Snoek & van Vugt, 1999), G7c and G7e (a retroviral envelope homologue; Snoek et al, 1996). Snoek et al (2000) have shown that the amino acid sequence of G7c is 28% identical to the Caenorhabditis elegans hemicentin precursor protein.…”

Section: Discussionmentioning

confidence: 99%

A novel locus affecting serum levels of IgG2a maps to the murine H2 region

Matthews

Christiansen

Price

2000

European Journal of Immunogenetics

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The effects of genes in the murine H2 region on basal immunoglobulin levels were investigated and ratios of IgG1/IgG2a were calculated, as low ratios indicate a Th1 cytokine mileu. H2b mice with B10 or BALB genetic backgrounds had higher levels of IgG2a than H2k and H2d congenic strains, and hence had low IgG1/IgG2a ratios. B10 (H2b) mice generally had high levels of IgG2b, IgG3, IgA and IgM, but this outcome was more variable. The high IgG2a phenotype was denoted Igis1 (Immunoglobulin isotype-1) and mapped telomeric of IEbeta using B10.A(4R) mice (high IgG2a) and B10.A(3R) and B10.A(5R) mice (low IgG2a). Further mapping in B10.A(2R), B10.A(1R) and B10.A(18R) mice placed Igis1 in the 27kb region between G7c and G7e.

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G7c , a novel gene in the mouse and human major histocompatibility complex class III region, possibly controlling lung tumor susceptibility

Cited by 13 publications

References 23 publications

SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi’s sarcoma

SNP screening of central MHC-identified HLA-DMB as a candidate susceptibility gene for HIV-related Kaposi’s sarcoma

mRNA expression analysis of cell cycle genes in islets of pregnant mice

A novel locus affecting serum levels of IgG2a maps to the murine H2 region

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