GeneCards Research Articles

Corneal endothelium: developmental strategies for regeneration

The main treatment available for restoration of the corneal endothelium is keratoplasty. This procedure is faced with several difficulties, including the shortage of donor tissue, post-surgical complications associated with the use of drugs to prevent immune rejection, and a significant increase in the occurrence of glaucoma. Recently, surgical procedures such as Descemet's stripping endothelial keratoplasty have focused on the transplant of corneal endothelium, yielding better visual results but still facing the need for donor tissue. The emergent strategies in the field of cell biology and tissue cultivation of corneal endothelial cells aim at the production of transplantable endothelial cell sheets. Cell therapy focuses on the culture of corneal endothelial cells retrieved from the donor, in the donor's cornea, followed by transplantation into the recipient. Recently, research has focused on overcoming the challenge of harvesting human corneal endothelial cells and the generation of new biomembranes to be used as cell scaffolds in surgical procedures. The use of corneal endothelial precursors from the peripheral cornea has also demonstrated to be effective and represents a valuable tool for reducing the risk of rejection in allogeneic transplants. Several animal model reports also support the use of adult stem cells as therapy for corneal diseases. Current results represent important progresses in the development of new strategies based on alternative sources of tissue for the treatment of corneal endotheliopathies. Different databases were used to search literature: PubMed, Google Books, MD Consult, Google Scholar, Gene Cards, and NCBI Books. The main search terms used were: 'cornea AND embryology AND transcription factors', 'human endothelial keratoplasty AND risk factors', '(cornea OR corneal) AND (endothelium OR endothelial) AND cell culture', 'mesenchymal stem cells AND cell therapy', 'mesenchymal stem cells AND cornea', and 'stem cells AND (cornea OR corneal) AND (endothelial OR endothelium)'.

Hierarchical modeling identifies novel lung cancer susceptibility variants in inflammation pathways among 10,140 cases and 11,012 controls

Recent evidence suggests that inflammation plays a pivotal role in the development of lung cancer. In this study, we used a two-stage approach to investigate associations between genetic variants in inflammation pathways and lung cancer risk based on genome-wide association study (GWAS) data. A total of 7,650 sequence variants from 720 genes relevant to inflammation pathways were identified using keyword and pathway searches from Gene Cards and Gene Ontology databases. In Stage 1, six GWAS datasets from the International Lung Cancer Consortium were pooled (4,441 cases and 5,094 controls of European ancestry), and a hierarchical modeling (HM) approach was used to incorporate prior information for each of the variants into the analysis. The prior matrix was constructed using (1) role of genes in the inflammation and immune pathways; (2) physical properties of the variants including the location of the variants, their conservation scores and amino acid coding; (3) LD with other functional variants and (4) measures of heterogeneity across the studies. HM affected the priority ranking of variants particularly among those having low prior weights, imprecise estimates and/or heterogeneity across studies. In Stage 2, we used an independent NCI lung cancer GWAS study (5,699 cases and 5,818 controls) for in silico replication. We identified one novel variant at the level corrected for multiple comparisons (rs2741354 in EPHX2 at 8p21.1 with p value = 7.4 × 10(-6)), and confirmed the associations between TERT (rs2736100) and the HLA region and lung cancer risk. HM allows for prior knowledge such as from bioinformatic sources to be incorporated into the analysis systematically, and it represents a complementary analytical approach to the conventional GWAS analysis.

M. Pneumoniae Is a Potential Trigger for Eosinophilic Esophagitis

Mycoplasma pneumoniae (MP) is suggested as a trigger of asthma. MP undergoes cyclic epidemics, has increasing macrolide resistance, increases IL-5 and VEGF and contains gene CARDS promoting TH2 inflammation. It has never before to our knowledge been implicated in eosinophilic esophagitis (EOE). We recently treated a 10 year old male for two months of acute onset morning vomiting and cough. He had multiple similarly ill contacts at school. He had failed reflux therapy. EGD showed over 50 eosinophils/HFP in all 3 levels, Ph-impedance probe was normal, MRI of CNS revealed severe pansinusitis.

The EuroGentest Clinical Utility Gene Cards continued

We are happy to announce that the EuroGentest Clinical Utility Gene Cards (CUGCs),1 first launched in this Journal by the end of 2010, will receive continuous support through EuGT2 (www.eurogentest.org) and the European Society of Human Genetics, at least until 2013. By this time, 300 of these guidelines for the application of genetic tests in clinical practice will have been created, and the majority of them will have received at least one update so as to closely reflect the state of the art. The first such updates are published in this issue of this Journal. CUGCs are built on the ACCE2 (analytical validity, clinical validity, clinical utility, and ethical, legal and social implications) evaluation process for genetic testing, and have an emphasis on the clinical utility aspects. The European Journal of Human Genetics continues to publish printed abstracts and offers free access to the full-text versions in its on-line editions. In addition, both the EuroGentest (www.eurogentest.org) and the Orphanet (www.orpha.net) websites provide links to all available gene cards. The EuroGentest website, in addition, gives monthly updated information on the status quo of the collection of CUGCs, whether completed, under preparation or still waiting to be initiated. The CUGCs seem to be well received by the scientific and clinical community: the projected rate of downloads from this Journal's website per gene card and year ranges between approximately 600 and 1500, with an average above 1000. The Clinical Utility Gene Cards represent either alternatives or complements to other collections serving similar purposes, in particular the NCBI GeneReviews (http://www.ncbi.nlm.nih.gov/books/NBK1116/) and the UK-GTN Gene Dossiers http://www.ukgtn.nhs.uk/gtn/Information/Services/Gene+Dossiers). Out of the 60 currently published CUGCs (http://www.eurogentest.org/web/info/public/unit3/geneCards.xhtml) 12 titles are exclusively present in the CUGC initiative, while only 7 titles are covered by all three initiatives. The overlap of the CUGC guidelines and the NCBI GeneReviews amounts to 39 diseases, CUGCs and UK-GTN Gene Dossiers to two diseases. In order to satisfy the highest standards of quality CUGCs will continue to pass through a carefully designed editorial process. Potential first authors are identified by the section editor, often based on external suggestions. Authors are selected on the basis of objective evidence of expertise, including their publication record. First authors are requested to invite a group of co-authors encouraging international representation. All CUGCs undergo peer review. The same procedure is applied to updates. We hope that this initiative will continue to be a useful service to the scientific and clinical community.

Using the BITOLA system to identify candidate genes for Parkinson's disease.

Complexity of multifactorial diseases as Parkinson's disease (PD) often complicate identifying causal genetic factors by traditional approaches such as positional cloning and candidate gene analyses. PD is etiologically and genetically complex disease and second most common neurodegenerative disorder after Alzheimer's disease. The most cases of PD are idiopathic and small growing subset of individuals have single gene defect as the cause. The main goal of this research was to identify the potential candidate genes for idiopathic PD by using biomedical discovery support system (BITOLA). For detecting the potential candidate genes for PD was used opened system of bioinformatics tool BITOLA. Data of chromosome location, tissue specific expression of potential candidate genes and their potential association with PD were obtained from Medline, Locus Link, Gene Cards and OMIM. By using BITOLA system is identified 17 genes as potential candidate genes for PD. The role of three genes (MAPT, PARK2, UCHL1) in PD were confirmed earlier. Discovering the novel candidate genes for multifactiorial diseases by using specially mentioned bioinformatics tool BITOLA could offer the new opportunity for researching genetics base of PD without using tissue samples of patients.

Identifying candidate genes for Parkinson’s disease by integrative genomics method

The recent studies of Parkinson's disease (PD) indicate that genetics and environmental factors may play an important role in developing of PD. Nowadays, the cell death and cell adhesion are pathogenetic mechanisms which could be related with PD. On the basis of relationship of those mechanisms with PD, the aim of this study was to identify new candidate genes for PD by integration of results of transcriptomics studies and results obtained by Biomedical Discovery Support System (BITOLA). For the detection of functional relationship between potential candidate gene and pathogenetic mechanisms associated with PD, we designed strategy of integration of results of transcriptomics studies with discovery approach in bibliographic data bases and BITOLA. Data of chromosome location, tissue-specific expression, function of potential candidate genes and their association with genetics disorders were obtained from Medline, Locus Link, Gene Cards and OMIM. Integration and comparison of results obtained using the BITOLA system and analysis of transcriptomics studies identified six genes (MAPT, UCHL1, NSF, CDC42, PARK2 and GFPT1) that occur simultaneously in both group of results. The function of genes NSF, CDC42 and GFPT1 in the pathogenesis of PD has not been studied yet. According to our result that aforementioned genes appeared in both groups of results and partially match the criteria set for the selection of candidate genes and their potential role in the development of PD, they should be tested by methods specifically intended for those three genes.

Computational Biological Analysis Reveals a Role for Nitric Oxide Synthase and Adiponectin in the Pathobiology of Insulin Resistance Syndrome and Coronary Artery Disease

Insulin resistance syndrome is a major risk factor for atherosclerosis and coronary heart disease (CAD). Endothelial dysfunction due to reduced nitric oxide generation is seen in both insulin resistance syndrome and CAD. Endothelial dysfunction also occurs in obesity, diabetes mellitus, and other cardiovascular diseases. In the present study, we employed multiple sequence alignment using Clustal W tool and constructed a phylogenetic tree using functional protein sequences extracted from NCBI and Gene cards. These studies showed that nitric oxide synthase and adiponectin play a major role in insulin resistance and coronary artery disease. This and other studies suggest that endothelial dysfunction is an early event in insulin resistance syndrome.

Aqueous Polymer Two-Phase Systems for the Proteomic Analysis of Plasma Membranes from Minute Brain Samples

Comprehensive knowledge about the plasma membrane protein profile of a given brain region, at defined developmental stages, will greatly foster the understanding of brain function and dysfunction. Protocols are required which selectively enrich plasma membranes from small brain regions, thereby resulting in high yields. Here, we present a suitable protocol that is based on aqueous polymer two-phase systems. It is material saving, easy to perform, fast, and low-priced. Evidence for its effectiveness was obtained by marker enzyme assays, immunoblot analyses, and mass spectrometry. Plasma membranes from all parts of the cells (somata, dendrites, and axons) were enriched, whereas there was a reduction of mitochondria and endoplasmic reticulum. The total of 15.0% of the initial activity of the plasma membrane marker was recovered, while the activity of the mitochondrial marker and the marker for the endoplasmic reticulum was 0.2% of the initial activity. Mass spectrometric analyses of proteins purified from approximately one-fourth of rat cerebellum (i.e., 80 mg of tissue) resulted in the identification of 525 different proteins, with 27.3% (gene ontology) or 38.2% (gene cards) being allocated to the plasma membrane. When accepting 4.7% of the initial mitochondrial marker activity and 2.9% of the initial activity of the marker for the endoplasmic reticulum as contaminations, the yield of the plasma membrane marker increased to 28.8%. Under these conditions, 586 different proteins were identified by mass spectrometry, 26.1-36.5% of which were plasma membrane proteins. Taken together, our protocol represents a powerful tool for the analysis of the plasma membrane subproteome of distinct brain regions.

WebWatch

BioTechniquesVol. 36, No. 4 WebWatchOpen AccessWebWatchKevin AhernKevin AhernSearch for more papers by this authorPublished Online:6 Jun 2018https://doi.org/10.2144/04364WW01AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInRedditEmail Maximum ZoomSeeing is not only believing, it is also entertaining, and that sets the tone for the Molecular Expressions microscopy site, hosted at Florida State University. With a flair for whimsy, the site's designers provide microscopic views of unusual items, like beer and ice cream, along with standard fare, such as cell and virus structures. There's more than just fun and games, however, to be had at the site. Watch confocal microscopic images come alive with Java-based virtual viewers that provide easy viewing of slices through tissues. Learn about modern microscopic techniques, such as laser scanning confocal microscopy. You can even adjust the focus, magnification, and contrast on microscopic creatures using the popular virtual scanning electron microscope.http://micro.magnet.fsu.edu/A Full DeckRemember the days of yore when the most important thing a kid had was a collection of sports cards of favorite players filled with vital stats? Fast forward to 2004 where the card metaphor has been borrowed big time in virtual form by the Weizmann Institute of Science. Their Gene Cards, a one-stop shop for gene-disease relationships, is a collection of over 53,000 records of gene-disease links. The “statistics” on Gene Cards make the information on baseball cards look pretty paltry, with DNA sequences, chromosome location, related genes, variants, protein structure analysis, and extensive transcription data, including tissue-specific expression data from microarrays.http://bioinformatics.weizmann.ac.il/cards/Cancer AnswersThe miracles of modern medicine are comforting. Antibiotics routinely stop infections in their tracks; vaccines prevent diseases before they start; and new technologies make surgery on beating hearts almost commonplace. Is it any wonder then that diseases, such as cancer, for which medical science offers no cure, strike fear in our hearts? Where can a person diagnosed with cancer turn to for information? Ten years ago the cancer specialists at the University of Pennsylvania asked themselves the same question and then answered it promptly with OncoLink, a web resource that describes various forms of the disease, explains how treatments work, and advises on how to cope with cancer. A section entitled “Ask the Experts” also gives concerned patients an opportunity to get questions answered online.http://www.oncolink.com/Genetic AssociationsThe need for more information about disease is not restricted to patients. Each day, scientific studies report new relationships between human genes and disease, forcing even the best researchers to scramble to keep abreast of their fields. The Genetic Associations web site, hosted by the NIH's National Institute on Aging, contains a database with a bewildering array of links between diseases, gene loci, and their respective online references. Curious about a protein such as insulin? Type the term into the site's search engine and scan through the six dozen different disease records retrieved for it. After locating your disease du jour, click the View button and explore the gene/disease links to popular databases, including NCBI, PubMed, LocusLink, and HapMap.http://geneticassociationdb.nih.govCache of the DayConsider the tiny zebrafish: a simple organism that can be inexpensively raised in lab aquariums, it goes through a complete developmental cycle from fertilized eggs to miniature fish in 72 hours, and it has a transparent embryo that can easily be manipulated. Consequently, zebrafish are hotter than a fish fry when it comes to studying vertebrate development. George Streisinger at the University of Oregon popularized the zebras as models for development back in the 1970s, and today, over 300 laboratories share his vision. The Zebrafish Information Network (ZFIN) was organized in 1994 at a Cold Spring Harbor meeting to meet the needs of these scientists and today serves as an online research database. Visitors can find mutants, locate strains, download sequences, examine gene expression patterns, generate maps, and more at the ZFIN site.http://zfin.org/FiguresReferencesRelatedDetails Vol. 36, No. 4 Follow us on social media for the latest updates Metrics Downloaded 90 times History Published online 6 June 2018 Published in print April 2004 Information© 2004 Author(s)PDF download

Human Gene-Centric Databases at the Weizmann Institute of Science: GeneCards, UDB, CroW 21 and HORDE.

Recent enhancements and current research in the GeneCards (GC) (http://bioinfo.weizmann.ac.il/cards/) project are described, including the addition of gene expression profiles and integrated gene locations. Also highlighted are the contributions of specialized associated human gene-centric databases developed at the Weizmann Institute. These include the Unified Database (UDB) (http://bioinfo.weizmann.ac.il/udb) for human genome mapping, the human Chromosome 21 database at the Weizmann Insti-tute (CroW 21) (http://bioinfo.weizmann.ac.il/crow21), and the Human Olfactory Receptor Data Explora-torium (HORDE) (http://bioinfo.weizmann.ac.il/HORDE). The synergistic relationships amongst these efforts have positively impacted the quality, quantity and usefulness of the GeneCards gene compendium.

GeneCards: integrating information about genes, proteins and diseases

GeneCards: integrating information about genes, proteins and diseases