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Inhibitor Gene (inhibitor + gene)
Selected AbstractsHereditary angioedema: The mutation spectrum of SERPING1/C1NH in a large Spanish cohort,HUMAN MUTATION, Issue 2 2005Olga Roche Abstract Hereditary angioedema (HAE) is a disease caused by defects in the C1 inhibitor gene (SERPING1/C1NH). We screened the entire C1NH gene for mutations in a large series of 87 Spanish families (77 with type I, and 10 with type II HAE) by SSCP, sequencing, Southern blotting, and quantitative multiplex PCR of short fluorescent fragments (QMPSF), and we characterized several defects at the mRNA level. We found large rearrangements in 13 families, and point mutations or microdeletions/insertions in 74 families. The 13 large rearrangements included nine exon deletions, of which at least eight were distinct, two were distinct exon duplications, and two were rearrangements whose precise nature could not be determined. We confirmed that exon 4 is particularly prone to rearrangements. Thirty-six mutations were unreported, and included 10 microdeletions/insertions, 10 missense, five nonsense, eight splicing, and three splicing or missense mutations. Moreover, we detected six novel uncharacterized sequence variants (USV). RT-PCR studies showed that in addition to several intronic splice site mutations tested, the exonic mutations c.882C>G and c.884T>G, located near the 3, end of exon 5, also produced exon skipping. This is the first evidence of SERPING1/C1NH mutations in coding regions that differ from the canonical splice sites that affect splicing, which suggests the presence of an exonic splicing enhancer (ESE) in exon 5. Hum Mutat 26(2), 1,10, 2005. © 2005 Wiley-Liss, Inc. [source] HAEdb: A novel interactive, locus-specific mutation database for the C1 inhibitor gene,HUMAN MUTATION, Issue 1 2005Lajos Kalmár Abstract Hereditary angioneurotic edema (HAE) is an autosomal dominant disorder characterized by episodic local subcutaneous and submucosal edema and is caused by the deficiency of the activated C1 esterase inhibitor protein (C1-INH or C1INH; approved gene symbol SERPING1). Published C1-INH mutations are represented in large universal databases (e.g., OMIM, HGMD), but these databases update their data rather infrequently, they are not interactive, and they do not allow searches according to different criteria. The HAEdb, a C1-INH gene mutation database (http://hae.biomembrane.hu) was created to contribute to the following expectations: 1) help the comprehensive collection of information on genetic alterations of the C1-INH gene; 2) create a database in which data can be searched and compared according to several flexible criteria; and 3) provide additional help in new mutation identification. The website uses MySQL, an open-source, multithreaded, relational database management system. The user-friendly graphical interface was written in the PHP web programming language. The website consists of two main parts, the freely browsable search function, and the password-protected data deposition function. Mutations of the C1-INH gene are divided in two parts: gross mutations involving DNA fragments >1 kb, and micro mutations encompassing all non-gross mutations. Several attributes (e.g., affected exon, molecular consequence, family history) are collected for each mutation in a standardized form. This database may facilitate future comprehensive analyses of C1-INH mutations and also provide regular help for molecular diagnostic testing of HAE patients in different centers. Hum Mutat 25:1,5, 2005. © 2004 Wiley-Liss, Inc. [source] New established melanoma cell lines: genetic and biochemical characterization of cell division cycleJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2003A Vozza ABSTRACT Background Cancer might be envisaged as the result of a genetic process causing the unregulated proliferation of a given cell as well as its inability to undergo differentiation and/or apoptosis. Alterations of genes regulating cell division cycle appear to play a key role in the development of human cancer. Objective On the bases of the above considerations, we decided to establish new cell lines from human melanoma specimens, in order to analyse the molecular alterations in primary preparations of malignant cells. Results The present paper describes two new established cell lines and their genetic and biochemical features. Both the melanoma cell lines show inactivation of the cyclin-dependent kinase inhibitor gene, CDKN2A/p16INK4A, thus demostrating that this alteration occurs in primary human melanomas. No other alterations were observable when we investigated several different cell cycle genes including those encoding cyclins, cyclin-dependent kinases and cyclin-dependent kinase inhibitors. Analyses at protein level by means of immunoblotting confirmed the results obtained at the genetic level. Moreover, the inducibility of a pivotal cyclin-dependent kinase inhibitor gene, namely p21CIP1 gene, was obtained by treating the cells with histone deacetylase inhibitors, namely butyrate and phenylbutyrate. Conclusions Our results suggest a primary role of cyclin-dependent kinase inhibitor genes inactivation in the origin of human melanoma and allow the proposal of new therapeutic strategies based on the transcriptional activation of p21CIP1 gene. [source] Unintended changes in protein expression revealed by proteomic analysis of seeds from transgenic pea expressing a bean ,-amylase inhibitor genePROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 18 2009Hancai Chen Abstract Seeds of genetically modified (GM) peas (Pisum sativum L.) expressing the gene for ,-amylase inhibitor-1 (,AI1) from the common bean (Phaseolus vulgaris L. cv. Tendergreen) exhibit resistance to the pea weevil (Bruchus pisorum). A proteomic analysis was carried out to compare seeds from GM pea lines expressing the bean ,AI1 protein and the corresponding ,AI1-free segregating lines and non-GM parental line to identify unintended alterations to the proteome of GM peas due to the introduction of the gene for ,AI1. Proteomic analysis showed that in addition to the presence of ,AI1, 33 other proteins were differentially accumulated in the ,AI1-expressing GM lines compared with their non-GM parental line and these were grouped into five expression classes. Among these 33 proteins, only three were found to be associated with the expression of ,AI1 in the GM pea lines. The accumulation of the remaining 30 proteins appears to be associated with Agrobacterium -mediated transformation events. Sixteen proteins were identified after MALDI-TOF-TOF analysis. About 56% of the identified proteins with altered accumulation in the GM pea were storage proteins including legumin, vicilin or convicilin, phaseolin, cupin and valosin-containing protein. Two proteins were uniquely expressed in the ,AI1-expressing GM lines and one new protein was present in both the ,AI1-expressing GM lines and their ,AI1-free segregating lines, suggesting that both transgenesis and transformation events led to demonstrable changes in the proteomes of the GM lines tested. [source] Frequent promoter hypermethylation of Wnt pathway inhibitor genes in malignant astrocytic gliomasINTERNATIONAL JOURNAL OF CANCER, Issue 11 2010Silke Götze Abstract Aberrant activation of wingless (Wnt) signaling is involved in the pathogenesis of various cancers. Recent studies suggested a role of Wnt signaling in gliomas, the most common primary brain tumors. We investigated 70 gliomas of different malignancy grades for promoter hypermethylation in 8 genes encoding members of the secreted frizzled-related protein (SFRP1, SFRP2, SFRP4, SFRP5), dickkopf (DKK1, DKK3) and naked (NKD1, NKD2) families of Wnt pathway inhibitors. All tumors were additionally analyzed for mutations in exon 3 of the ,-catenin gene (CTNNB1). While none of the tumors carried CTNNB1 mutations, we found frequent promoter hypermethylation of Wnt pathway inhibitor genes, with at least one of these genes being hypermethylated in 6 of 16 diffuse astrocytomas (38%), 4 of 14 anaplastic astrocytomas (29%), 7 of 10 secondary glioblastomas (70%) and 23 of 30 primary glioblastomas (77%). Glioblastomas often demonstrated hypermethylation of 2 or more analyzed genes. Hypermethylation of SFRP1, SFRP2 and NKD2 each occurred in more than 40% of the primary glioblastomas, while DKK1 hypermethylation was found in 50% of secondary glioblastomas. Treatment of SFRP1-, SFRP5-, DKK1-, DKK3-, NKD1- and NKD2 -hypermethylated U87-MG glioblastoma cells with 5-aza-2,-deoxycytidine and trichostatin A resulted in increased expression of each gene. Furthermore, SFRP1 -hypermethylated gliomas showed significantly lower expression of the respective transcripts when compared with unmethylated tumors. Taken together, our results suggest an important role of epigenetic silencing of Wnt pathway inhibitor genes in astrocytic gliomas, in particular, in glioblastomas, with distinct patterns of hypermethylated genes distinguishing primary from secondary glioblastomas. [source] | ||||||||||