Search results for "Allele"
showing 10 items of 1006 documents
The c.43_44insCTG variation in PCSK9 is associated with low plasma LDL-cholesterol in a Caucasian population.
2006
Abstract The genetic etiology of familial hypobetalipoproteinemia (FHBL) is unclear in the majority of cases. Mutations in apolipoprotein B (APOB) are the only confirmed causes of FHBL. Recently, loss-of-function mutations of PCSK9 gene have been shown to be associated with the hypocholesterolemia phenotype. Our primary goal was to confirm that mutations in PCSK9 could be another cause of FHBL. Using the sequencing approach, we found that the c.43_44insCTG variation in PCSK9, a common in-frame insertion in both African American and Caucasian populations, is associated with the hypocholesterolemia phenotype in three FHBL families. Then we tested whether this variation could be associated wit…
Prevalence of ANGPTL3 and APOB gene mutations in subjects with combined hypolipidemia.
2012
Objective— Mutations of the ANGPTL3 gene have been associated with a novel form of primary hypobetalipoproteinemia, the combined hypolipidemia (cHLP), characterized by low total cholesterol and low HDL-cholesterol levels. The aim of this work is to define the role of ANGPTL3 gene as determinant of the combined hypolipidemia phenotype in 2 large cohorts of 913 among American and Italian subjects with primary hypobetalipoproteinemia (total cholesterol <5th percentile). Methods and Results— The combined hypolipidemia cut-offs were chosen according to total cholesterol and HDL-cholesterol levels reported in the ANGPTL3 kindred described to date: total cholesterol levels, <2nd percentile …
The C(-260)T gene polymorphism in the promoter of the CD14 monocyte receptor gene is not associated with acute myocardial infarction.
2003
CD surface molecules mediates cell activation and signaling. In particular, CD14 on blood monocytes mediate monocyte/macrophage activation by lipopolysaccharide. Lipopolysaccharide and its receptor, CD14, have been implicated in atherogenesis. It has been recently shown that a C(-260)T polymorphism in the promoter of the CD14 receptor may be a risk factor for coronary artery disease. Recently this association has been questioned because no increased risk was found with the T allele, even in the homozygous state. In the present study we investigated a possible association between the C(-260)T polymorphism in the CD14 promoter and acute myocardial infarction. Two hundred and thrteen patients …
Polymorphism of immunoglobulin enhancer element HS1,2A: allele *2 associates with systemic sclerosis. Comparison with HLA‐DR and DQ allele frequency
2007
OBJECTIVE: To investigate the relationship of the polymorphic enhancer HS1,2 central to the 3' enhancer complex regulatory region (IgH3'EC) of the immunoglobulin heavy chain genes with systemic sclerosis (SSc) disease and compare it with HLA-DR and DQ associations. METHODS: A total of 116 patients with SSc were classified as diffuse (dSSc) or limited (lSSc), and as carriers of antitopoisomerase I (anti-Scl70) or anticentromere (ACA) antibodies. Allele and genotype frequencies were assessed in the population as a whole and in the two major subsets, dSSc and lSSc. The concentration of peripheral blood immunoglobulin levels was also determined and analysed according to the genotypes. RESULTS: …
DNA Commission of the International Society of Forensic Genetics: recommendations on forensic analysis using Y-chromosome STRs
2001
During the past few years, the DNA Commission of the International Society of Forensic Genetics has published a series of documents providing guidelines and recommendations concerning the application of DNA polymorphisms to the problems of human identification. This latest report addresses a relatively new area - namely, Y-chromosome polymorphisms, with particular emphasis on short tandem repeats (STRs). This report addresses nomenclature, use of allelic ladders, population genetics and reporting methods.
CD8 T cell-evasive functions of human cytomegalovirus display pervasive MHC allele specificity, complementarity, and cooperativity.
2014
Abstract Immunoevasive proteins (“evasins”) of human CMV (HCMV) modulate stability and localization of MHC class I (MHC I) molecules, and their supply of antigenic peptides. However, it is largely unknown to what extent these evasins interfere with recognition by virus-specific CD8 T cells. We analyzed the recognition of HCMV-infected cells by a panel of CD8 T cells restricted through one of nine different MHC I allotypes. We employed a set of HCMV mutants deleted for three or all four of the MHC I modulatory genes US2, US3, US6, and US11. We found that different HCMV evasins exhibited different allotype-specific patterns of interference with CD8 T cell recognition of infected cells. In con…
Immunoproteasome LMP2 60HH Variant Alters MBP Epitope Generation and Reduces the Risk to Develop Multiple Sclerosis in Italian Female Population
2010
BackgroundAlbeit several studies pointed out the pivotal role that CD4+T cells have in Multiple Sclerosis, the CD8+ T cells involvement in the pathology is still in its early phases of investigation. Proteasome degradation is the key step in the production of MHC class I-restricted epitopes and therefore its activity could be an important element in the activation and regulation of autoreactive CD8+ T cells in Multiple Sclerosis.Methodology/principal findingsImmunoproteasomes and PA28-alphabeta regulator are present in MS affected brain area and accumulated in plaques. They are expressed in cell types supposed to be involved in MS development such as neurons, endothelial cells, oligodendroc…
Molecular, genetic, and functional analysis of homozygous C8 beta-chain deficiency in two siblings.
1998
Abstract C8 deficiency is associated with an increased susceptibility to neisserial infections. We present a case of an 11 year old boy who suffered from infection with Neisseria meningitidis . Medical history of the patient and his family ( n = 5) did not indicate any previous immunodeficiency symptoms. Results from the analysis of phagocyte and lymphocyte functions were within the normal range. No hemolytic activities of the classical (CH50) and the alternative (APH50) pathways of complement were measurable, and SC5b-9 protein complexes could not be detected in the patient's plasma. Further analysis by highly sensitive ELISA and functional assays revealed a complete deficiency of C8. Upon…
Mutations in the PDS Gene in German Families with Pendred’s Syndrome: V138F Is a Founder Mutation
2003
Pendred's syndrome, an autosomal-recessive condition characterized by congenital sensorineural hearing loss and goiter, is caused by mutations in the PDS gene. Located on chromosome 7q22-q31, it encodes a chloride-iodide transporter expressed in the thyroid, inner ear, and kidney. We investigated the PDS gene of six affected individuals from four unrelated families with Pendred's syndrome by direct sequencing. PDS mutations were identified in homozygous or compound heterozygous state in all six cases. A homozygous missense mutation leading to the amino acid substitution S133T was detected in a family of Turkish origin. The mutations found in the other affected individuals, who originate fro…
Lysosomal Signaling Licenses Embryonic Stem Cell Differentiation via Inactivation of Tfe3
2019
International audience; Self-renewal and differentiation of pluripotent murine embryonic stem cells (ESCs) is regulated by extrinsic signaling pathways. It is less clear whether cellular metabolism instructs developmental progression. In an unbiased genome-wide CRISPR/Cas9 screen, we identified components of a conserved amino-acid-sensing pathway as critical drivers of ESC differentiation. Functional analysis revealed that lysosome activity, the Ragulator protein complex, and the tumor-suppressor protein Folliculin enable the Rag GTPases C and D to bind and seclude the bHLH transcription factor Tfe3 in the cytoplasm. In contrast, ectopic nuclear Tfe3 represses specific developmental and met…