Search results for "Bioinformatics"
showing 10 items of 1632 documents
Clinical relevance of polymorphic markers of arterial thrombosis.
1997
Case-control and cross-sectional studies show that some common molecular variations (polymorphisms) of genes coding for proteins involved in atherosclerosis and thrombosis are often present in subjects who have experienced cerebrovascular or cardiovascular events. The clinical impact of the majority of polymorphic markers is disputed by prospective reports. In contrast, their pathophysiological implications and their role in monitoring parameters that are difficult to be checked by alternative means, are documented by the large majority of the reports. From the evidence available, there may be suggestion for further impact of polymorphic markers in vascular medicine. To substantiate this, n…
Pro-Inflammatory Genetic Markers of Atherosclerosis
2013
Atherosclerosis (AS) is a chronic, progressive, multifactorial disease mostly affecting large and medium-sized elastic and muscular arteries. It has formerly been considered a bland lipid storage disease. Currently, multiple independent pathways of evidence suggest this pathological condition is a peculiar form of inflammation, triggered by cholesterol-rich lipoproteins and influenced both by environmental and genetic factors. The Human Genome Project opened up the opportunity to dissect complex human traits and to understand basic pathways of multifactorial diseases such as AS. Population-based association studies have emerged as powerful tools for examining genes with a role in common mul…
Gene Therapy in Rare Respiratory Diseases: What Have We Learned So Far?
2020
Gene therapy is an alternative therapy in many respiratory diseases with genetic origin and currently without curative treatment. After five decades of progress, many different vectors and gene editing tools for genetic engineering are now available. However, we are still a long way from achieving a safe and efficient approach to gene therapy application in clinical practice. Here, we review three of the most common rare respiratory conditions—cystic fibrosis (CF), alpha-1 antitrypsin deficiency (AATD), and primary ciliary dyskinesia (PCD)—alongside attempts to develop genetic treatment for these diseases. Since the 1990s, gene augmentation therapy has been applied in multiple clinical tria…
Friedreich Ataxia: An Update on Animal Models, Frataxin Function and Therapies
2009
Friedreich ataxia (FRDA) is an autosomal recessive progressively debilitating degenerative disease that principally affects the nervous system and the heart. Although FRDA is considered a rare disease, is the most common inherited ataxia. It is caused by loss-of-function mutations in the FXN gene, mainly an expanded GAA triplet repeat in the intron 1. The genetic defect results in the reduction of frataxin levels, a protein targeted to the mitochondria. Frataxin deficiency leads to mitochondrial dysfunction, oxidative damage and iron accumulation. Studies of the yeast and animal models of the disease have led to propose several different roles for frataxin. Animal models have also been impo…
Screening for multiple hereditary hypercoagulability factors using the amplification refractory mutation system
2003
Many hereditary factors have been implicated in the development of arterial and/or venous thromboembolic diseases. A number of these risk factors can be identified by the amplification refractory mutation system (ARMS). However, the underlying technical conditions for performing ARMS are highly variable, and depend on which risk factors are being analyzed. We have now developed a novel ARMS-based system to simultaneously screen for multiple hypercoagulability factors under identical PCR conditions. This can greatly simplify the process of screening for hereditary hypercoagulability.
Homozygous Truncating Intragenic Duplication in TUSC3 Responsible for Rare Autosomal Recessive Nonsyndromic Intellectual Disability with No Clinical …
2014
Intellectual disability (ID), which affects around 2–3% of the general population, is classically divided into syndromic and nonsyndromic forms, with several modes of inheritance. Nonsyndromic autosomal recessive ID (NS-ARID) appears extremely heterogeneous with numerous genes identified to date, including inborn errors of metabolism. The TUSC3 gene encodes a subunit of the endoplasmic reticulum (ER)-bound oligosaccharyltransferase complex, which mediates a key step of N-glycosylation. To date, only five families with NS-ARID and TUSC3 mutations or rearrangements have been reported in the literature. All patients had speech delay, moderate-to-severe ID, and moderate facial dysmorphism. Micr…
SLC23A2 Gene Variation, Vitamin C Levels, and Glaucoma
2014
Abstract Primary open-angle glaucoma (POAG) is a multifactorial disease in which both genetic and environmental factors are involved. Among the environmental factors associated with POAG, nutritional factors are particularly important since nutrition is essential for maintaining good health. Researchers can study the interactions between nutrition and genes by means of nutritional genomics, but nutrigenomics studies regarding eye diseases are very scarce. This research group recently published one of the first studies on nutrigenomics in POAG. It was found that the rs1279683 polymorphism in the SLC23A2 gene, which encodes a vitamin C transporter, is associated with a higher risk of POAG. Si…
Cell cycle: Aetiology of age-associated aneuploidy: a mechanism based on the 'free radical theory of ageing'
1995
A general model is put forward to explain the mechanism by which age-associated aneuploidies are produced. This is based on the free radical theory of ageing, which assumes a rise in oxidative stress with age. It is proposed that determination of indicators of oxidative stress in oocytes from various sources could be a first step in the testing of this hypothesis.
Novel insights in the genetics of HCC recurrence and advances in transcriptomic data integration.
2011
Background & Aims: In approximately 70% of patients with hepatocellular carcinoma (HCC) treated by resection or ablation, disease recurs within 5 years. Although gene expression signatures have been associated with outcome, there is no method to predict recurrence based on combined clinical, pathology, and genomic data (from tumor and cirrhotic tissue). We evaluated gene expression signatures associated with outcome in a large cohort of patients with early stage (Barcelona-Clinic Liver Cancer 0/A), single-nodule HCC and heterogeneity of signatures within tumor tissues. Methods:We assessed 287 HCC patients undergoing resection and tested genome-wide expression platforms using tumor (n = 287)…
Genetic Variability of Hepatitis C Virus before and after Combined Therapy of Interferon plus Ribavirin
2008
We present an analysis of the selective forces acting on two hepatitis C virus genome regions previously postulated to be involved in the viral response to combined antiviral therapy. One includes the three hypervariable regions in the envelope E2 glycoprotein, and the other encompasses the PKR binding domain and the V3 domain in the NS5A region. We used a cohort of 22 non-responder patients to combined therapy (interferon alpha-2a plus ribavirin) for which samples were obtained before initiation of therapy and after 6 or/and 12 months of treatment. A range of 25-100 clones per patient, genome region and time sample were sequenced. These were used to detect general patterns of adaptation, t…