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At least 325 records · Page 18Linked to original sources
PubMed1999

Mapping of a first locus for autosomal dominant myxomatous mitral-valve prolapse to chromosome 16p11.2-p12.1.

Myxomatous mitral-valve prolapse (MMVP), also called Barlow disease, is a common cardiac abnormality and affects up to 5% of the population. It is characterized by an excess of tissue that leads to billowing of the mitral leaflets, sometimes complicated by prolapse. Typical histological findings include myxomatous degeneration and degradation of collagen and elastin. Previous reports have proposed an autosomal dominant inheritance of the trait, with age- and sex-dependent expression. By systematic echocardiographic screening of the first-degree relatives of 17 patients who underwent mitral-valve repair, we have identified four pedigrees showing such an inheritance. Genomewide linkage analysis of the most informative pedigree (24 individuals, three generations) showed a significant linkage for markers mapping to chromosome 16p, with a two-point maximum LOD score for D16S3068 (Zmax=3.30 at straight theta=0). Linkage to D16S3068 was confirmed in a second family (Zmax=2.02 at straight theta=0) but was excluded for the two remaining families, thus demonstrating the genetic heterogeneity of the disease. Multipoint linkage analysis performed, with nine additional markers, on the two families with linkage gave maximum multipoint LOD scores of 5.45 and 5.68 for D16S3133, according to a conservative and a stringent model, respectively. Haplotype analysis defined a 5-cM minimal MMVP-1 locus between D16S3068 (16p11.2) and D16S420 (16p12. 1) and a 34-cM maximal interval between D16S404 and D16S3068 when recombination events were taken into account only in affected individuals. The identification of this locus represents a first step toward a new molecular classification of mitral-valve prolapse.

Chromosome Mapping↗
PubMed2005

Modern approaches to age-old questions about thyroid tumors.

There is a compelling need for improvement in the diagnosis of thyroid nodules, in predicting thyroid cancer prognosis and, in the treatment of recurrent well-differentiated and anaplastic thyroid cancer. In this review we discuss the impact of genomic technologies such as microarrays, SAGE, and proteomics on the diagnosis, prognosis and treatment of thyroid cancer. Gene expression profiling using these technologies has shown promising results in the molecular classification of different types of cancer, including thyroid. Furthermore, microarrays have been successfully used to identify prognostic markers in other cancer-types, offering the possibility to better tailor thyroid cancer treatment schemes. Lastly, novel therapeutic targeting against tyrosine kinases have shown promising results in the treatment of several cancers and might prove to be beneficial for patients with recurrent or undifferentiated thyroid cancer.

Humans↗
PubMed2005

Molecular variation and fingerprinting of Leucadendron cultivars (Proteaceae) by ISSR markers.

BACKGROUND AND AIMS: There are more than 80 species of Leucadendron and most are used as cut flowers. Currently, more than 100 cultivars are used by industry and many of them are interspecific hybrids. The origin of most cultivars is unclear and their genetic diversity and relationships have not been studied. This investigation was carried out to evaluate the genetic variation and relationships among 30 Leucadendron cultivars. METHODS: ISSR markers were applied to determine the genetic variation and to discriminate Leucadendron cultivars. Sixty-four ISSR primers were screened and 25 primers were selected for their ability to produce clear and reproducible patterns of multiple bands. KEY RESULTS: A total of 584 bands of 305-2400 bp were amplified, of which 97 % were polymorphic. A dendrogram generated using the Unweighted Pair Group Method with Arithmetic Average based on a distance measure of total character difference showed that the Leucadendron cultivars clustered into two main groups. Twenty-four of the 30 cultivars can be unequivocally differentiated, but identical profiles were observed for three cultivar pairs, 'Katie's Blush' and 'Silvan Red', 'Highlights' and 'Maui Sunset', and 'Yellow Crest' and 'Yellow Devil'. CONCLUSIONS: ISSR profiling is a powerful method for the identification and molecular classification of Leucadendron cultivars. A fingerprinting key was generated based on the banding patterns produced using two ISSR primers (UBC856 and UBC857). In addition cultivar-specific ISSR bands were obtained for 17 of the 30 Leucadendron cultivars tested.

DNA Fingerprinting↗
PubMed2004

Partial Cox regression analysis for high-dimensional microarray gene expression data.

MOTIVATION: An important application of microarray technology is to predict various clinical phenotypes based on the gene expression profile. Success has been demonstrated in molecular classification of cancer in which different types of cancer serve as categorical outcome variable. However, there has been less research in linking gene expression profile to censored survival outcome such as patients' overall survival time or time to cancer relapse. In this paper, we develop a partial Cox regression method for constructing mutually uncorrelated components based on microarray gene expression data for predicting the survival of future patients. RESULTS: The proposed partial Cox regression method involves constructing predictive components by repeated least square fitting of residuals and Cox regression fitting. The key difference from the standard principal components of Cox regression analysis is that in constructing the predictive components, our method utilizes the observed survival/censoring information. We also propose to apply the time-dependent receiver operating characteristic curve analysis to evaluate the results. We applied our methods to a publicly available dataset of diffuse large B-cell lymphoma. The outcomes indicated that combining the partial Cox regression method with principal components analysis results in parsimonious model with fewer components and better predictive performance. We conclude that the proposed partial Cox regression method can be very useful in building a parsimonious predictive model that can accurately predict the survival of future patients based on the gene expression profile and survival times of previous patients. AVAILABILITY: R codes are available upon request.

Biomarkers, Tumor↗
PubMed2005

Penalized Cox regression analysis in the high-dimensional and low-sample size settings, with applications to microarray gene expression data.

MOTIVATION: An important application of microarray technology is to relate gene expression profiles to various clinical phenotypes of patients. Success has been demonstrated in molecular classification of cancer in which the gene expression data serve as predictors and different types of cancer serve as a categorical outcome variable. However, there has been less research in linking gene expression profiles to the censored survival data such as patients' overall survival time or time to cancer relapse. It would be desirable to have models with good prediction accuracy and parsimony property. RESULTS: We propose to use the L(1) penalized estimation for the Cox model to select genes that are relevant to patients' survival and to build a predictive model for future prediction. The computational difficulty associated with the estimation in the high-dimensional and low-sample size settings can be efficiently solved by using the recently developed least-angle regression (LARS) method. Our simulation studies and application to real datasets on predicting survival after chemotherapy for patients with diffuse large B-cell lymphoma demonstrate that the proposed procedure, which we call the LARS-Cox procedure, can be used for identifying important genes that are related to time to death due to cancer and for building a parsimonious model for predicting the survival of future patients. The LARS-Cox regression gives better predictive performance than the L(2) penalized regression and a few other dimension-reduction based methods. CONCLUSIONS: We conclude that the proposed LARS-Cox procedure can be very useful in identifying genes relevant to survival phenotypes and in building a parsimonious predictive model that can be used for classifying future patients into clinically relevant high- and low-risk groups based on the gene expression profile and survival times of previous patients.

Biomarkers, Tumor↗
PubMed2006

Analysis of sample set enrichment scores: assaying the enrichment of sets of genes for individual samples in genome-wide expression profiles.

MOTIVATION: Gene expression profiling experiments in cell lines and animal models characterized by specific genetic or molecular perturbations have yielded sets of genes annotated by the perturbation. These gene sets can serve as a reference base for interrogating other expression datasets. For example, a new dataset in which a specific pathway gene set appears to be enriched, in terms of multiple genes in that set evidencing expression changes, can then be annotated by that reference pathway. We introduce in this paper a formal statistical method to measure the enrichment of each sample in an expression dataset. This allows us to assay the natural variation of pathway activity in observed gene expression data sets from clinical cancer and other studies. RESULTS: Validation of the method and illustrations of biological insights gleaned are demonstrated on cell line data, mouse models, and cancer-related datasets. Using oncogenic pathway signatures, we show that gene sets built from a model system are indeed enriched in the model system. We employ ASSESS for the use of molecular classification by pathways. This provides an accurate classifier that can be interpreted at the level of pathways instead of individual genes. Finally, ASSESS can be used for cross-platform expression models where data on the same type of cancer are integrated over different platforms into a space of enrichment scores. AVAILABILITY: Versions are available in Octave and Java (with a graphical user interface). Software can be downloaded at http://people.genome.duke.edu/assess.

Algorithms↗
PubMed1973

The suppression of AD-3B mutants by supersuppressors in Neurospora crassa.

The action of eight suppersuppressors has been tested on 76 ad-3B mutants which were induced by base-pair transition mutagens. Thirteen mutants were found to be suppressible by at least one ssu gene. Most of the suppressible mutants were found to belong to a class in which one would expect to find nonsense mutants (polar complementing or noncomplementing classes, with AT at the mutant site). However, suppression was observed in other classes, including those containing presumed missense mutants. The specificity of the suppressors and the criteria for molecular classification of the mutants are discussed.

Alleles↗
PubMed2001

Mutation of the gene encoding the enamel-specific protein, enamelin, causes autosomal-dominant amelogenesis imperfecta.

Amelogenesis imperfecta (AI) is a group of inherited defects of dental enamel formation that shows both clinical and genetic heterogeneity. To date, mutations in the gene encoding amelogenin have been shown to underlie a subset of the X-linked recessive forms of AI. Although none of the genes underlying autosomal-dominant or autosomal-recessive AI have been identified, a locus for a local hypoplastic form has been mapped to human chromosome 4q11-q21. In the current investigation, we have analysed a family with an autosomal-dominant, smooth hypoplastic form of AI. Our results have shown that a splicing mutation in the splice donor site of intron 7 of the gene encoding the enamel-specific protein enamelin underlies the phenotype observed in this family. This is the first autosomal-dominant form of AI for which the genetic mutation has been identified. As this type of AI is clinically distinct from that localized previously to chromosome 4q11-q21, these findings highlight the need for a molecular classification of this group of disorders.

Amelogenesis Imperfecta↗
PubMed2005

FlyBase: genes and gene models.

FlyBase (http://flybase.org) is the primary repository of genetic and molecular data of the insect family Drosophilidae. For the most extensively studied species, Drosophila melanogaster, a wide range of data are presented in integrated formats. Data types include mutant phenotypes, molecular characterization of mutant alleles and aberrations, cytological maps, wild-type expression patterns, anatomical images, transgenic constructs and insertions, sequence-level gene models and molecular classification of gene product functions. There is a growing body of data for other Drosophila species; this is expected to increase dramatically over the next year, with the completion of draft-quality genomic sequences of an additional 11 Drosophila species.

Animals↗
PubMed2003

Genotype-based phenotyping heralds a new taxonomy for inflammatory bowel disease.

Inflammatory bowel disease (IBD) has traditionally been categorized as either ulcerative colitis or Crohn disease on the basis of clinical, radiologic, and histologic criteria. Within these diseases, however, significant heterogeneity is observed, suggesting the existence of phenotypic subtypes, based on features such as location and behavior of disease. Evidence for a possible genetic basis of these subgroups first emerged in the 1990s from epidemiologic studies in multiply affected families. Recent advances in our understanding of the genetics of IBD, in particular the identification of NOD2/CARD15, have provided the opportunity to explore the genetic basis for this heterogeneity. This article reviews recent studies investigating the contribution of genetics to IBD phenotype. Although many of the genes remain unidentified, the emerging data suggests that IBD comprises a heterogeneous family of oligogenic inflammatory disorders in which the specific clinical manifestations of disease in any individual are determined by the interaction of genetic and environmental factors. These data have validated the approach of classifying patients into accurately defined clinical subgroups, and they raise the possibility that a genetic basis for the observed disease heterogeneity may account for the discrepant findings from earlier genetic studies. A future molecular classification will provide the framework to understanding the different biologic mechanisms that underlie the clinical subgroups of IBD and, by patient stratification, permit the unraveling of the complex interaction between the genetic and environmental causes of disease.

Journal Article↗
PubMed2003

Human immunodeficiency virus associated lymphoma.

PURPOSE OF REVIEW: Human immunodeficiency virus (HIV) infection is known to be associated with an increased risk of systemic nonHodgkin lymphoma, Hodgkin disease, and primary central nervous lymphoma (PCNSL). The purpose of this review is to highlight recent advances in the diagnosis and management of lymphoma occurring in patients with HIV infection. RECENT FINDINGS: Lymphoma occurring in patients with HIV infection has been associated with a very poor prognosis. Recently reported studies have provided new information regarding the influence of highly active antiretroviral therapy (HAART) on the development and clinical presentation of lymphoma, the feasibility of combining HAART with standard chemotherapy, the molecular classification of lymphoma, the role of rituximab in the management of lymphoma, and the use of novel treatment strategies for the treatment of Hodgkin disease. SUMMARY: The improved prognosis for patients with HIV-associated lymphoma in the post-HAART era indicates that therapeutic interventions may be potentially curative, and represent a shift away from therapeutic nihilism and reduced-intensity treatment approaches that have been employed in the recent past.

Anti-HIV Agents↗
PubMed1999

Expression of activated epidermal growth factor receptors, Ras-guanosine triphosphate, and mitogen-activated protein kinase in human glioblastoma multiforme specimens.

OBJECTIVE: Amplification of the epidermal growth factor receptor (EGFR) is a common event in the molecular pathogenesis of high-grade astrocytic tumors, occurring in 50% of glioblastoma multiforme (GBM) cases. A subset of GBMs also express a constitutively phosphorylated truncated receptor (EGFRvIII). Expression of transfected EGFRvIII in cells has been reported to activate the Ras-mitogen-activated protein kinase pathway and to provide a growth advantage. Novel therapeutic agents targeting signal transduction pathways are entering early clinical trials; determination of which GBMs express EGFRvIII might help identify patients who might benefit from these biological agents. METHODS: A cohort of 15 flash-frozen surgical specimens (12 GBMs, 2 gliosarcomas, and 1 adult low-grade glioma) were evaluated for EGFR and EGFRvIII expression and for EGFR activation status using immunohistochemical (IHC) analysis, Western blotting, and reverse transcription-polymerase chain reaction assays. Levels of activated Ras-guanosine triphosphate were measured using a nonradioactive luciferase-based technique. Mitogen-activated protein kinase activation was determined using a myelin basic protein assay. IHC analysis was performed on paraffin-embedded, formalin-fixed, pathological specimens. Normal control samples included white matter specimens distal to tumors (n = 5), a sample obtained during a lobectomy for treatment of epilepsy (n = 1), and cultured fetal human astrocytes (n = 1). RESULTS: We demonstrated higher levels of activated Ras and mitogen-activated protein kinase in GBM specimens, compared with normal brain tissue or the low-grade glioma. There was a very good correlation between results obtained using specialized molecular techniques and those obtained using routine IHC techniques. Screening for EGFRvIII expression may be of prognostic importance, because patients with EGFRvIII-positive tumors exhibited shorter life expectancies (mean survival time for patients with EGFRvIII-positive tumors, 4.5 +/- 0.6 mo; mean survival time for patients with EGFRvIII-negative tumors, 11.2 +/- 0.9 mo). CONCLUSION: We demonstrated that routine IHC techniques using commercially available antibodies are capable of identifying which GBM specimens express EGFRvIII and whether the EGFRs are activated. Such a molecular classification of GBMs might allow us to determine which patients might benefit from biologically targeted therapies. In addition, characterization of specimens with respect to their EGFRvIII status seems to be of prognostic value.

Adult↗
PubMed1998

Non-Alzheimer degenerative dementias.

Recent progress in diagnostic criteria of non-Alzheimer degenerative dementias is reviewed. These dementias comprise frontotemporal dementias (including hereditary dementias), primary progressive aphasia and anarthria, corticobasal degeneration, progressive supranuclear palsy and dementia with Lewy bodies. The approach of studying these diseases has changed considerably with genetic and biochemical analyses. A molecular classification is suggested and the clinical significance of this classification is discussed.

Dementia↗
PubMed2000

Epidemiology of brain tumors.

Primary brain tumor incidence and survival patterns are emerging, assisted by progress in molecular classification. Evidence is accumulating to suggest that infectious diseases may affect the risk of developing a brain tumor, although data require clarification. Other promising research directions include evaluating the role of diet and allergic conditions in reducing brain tumor risk.

Brain Neoplasms↗
PubMed2001

Genomic approaches to the pathogenesis of hematologic malignancy.

Recent advances in genome technologies and computational biology have facilitated genome-wide views of hematologic malignancy. In particular, comparative gene expression methods using DNA microarrays have allowed for the analysis of gene expression patterns in both primary patient material and model systems of hematopoietic development. This review provides an overview of the basic technologies underlying these approaches and provides a summary of recent progress in the genome-wide molecular classification of human acute leukemias and lymphomas and of initial attempts to define oncogene-mediated transcriptional programs using DNA microarrays.

Acute Disease↗
PubMed1998

Streptomyces thermogriseus, a new species of the genus Streptomyces from soil, lake and hot-spring.

Many thermophilic actinomycetes were isolated from samples collected from a hot-spring, lake and soil in Yunnan, China. Chemical and molecular classification of four selected strains of thermophilic Streptomyces with an upper limited growth temperature of 65-68 degrees C and autolytic characteristics was carried out. A new species, Streptomyces thermogriseus sp. nov. is described. The type strain is Y-14046T (= CCTCC AA97014T).

China↗
PubMed2004

Assessing health-related quality-of-life in individuals with haemophilia in China.

Haemophilia is a group of inherited, congenital diseases present all through the life. Those disorders are associated with a chronic burden of morbidity punctuated by episodes of acute deterioration in health-related quality-of-life (HR-QL). The significances of assessing HR-QL in individuals with haemophilia as an important component of the clinical database have gained increasing recognition in recent years. To the best of our knowledge, reports on the HR-QL of Chinese patients with haemophilia are not available. The purpose of this paper was to assess the HR-QL of patients with haemophilia in China. In order to do this, 179 patients with haemophilia (age 16-70) were mailed China quality-of-life questionnaire, which was designed specially for this study taking into account the culture characters of Chinese. Compared with the normal male general population, individuals with haemophilia experienced significantly lower levels of HR-QL and within the subgroups of patients, there was a gradation of HR-QL from mild < moderate < severe haemophilia patients. Age, clinical severity, degree of arthropathy, hepatitis status, salary and mean annual expenditure for replacement therapy were predictors of HR-QL. Clinical severity of the disease manifestation rather than the severity of the disease based on molecular classification was a factor that negatively influenced the HR-QL of patients with haemophilia. Arthropathies of patients with haemophilia in China were more severe than that in western countries because of the poorer medical care and were associated with their lower income and therapy cost. A large number of patients never had hepatitis or HIV serological examination. The exact prevalence of hepatitis and HIV was difficult to obtain and the HR-QL of hepatitis and HIV positive patients required further study.

Adolescent↗
PubMed2007

Proteomics analysis in lung cancer: challenges and opportunities.

Recent technological developments in proteomic analysis are bringing us new insights into the molecular classification of tumours. Although proteomic analysis in cancer profiling is still under development both in terms of the instruments used and the data analytical tools, this method has great potential advantages for the analysis of biospecimens of many types. Direct measurement of abnormally expressed or modified proteins in the tumour tissue and/or patient blood may be an effective approach for discovering new biomarkers. Proteomics has the significant advantage of being able to discern not only changes in expression levels but also in post-translational modifications. Thus, the proteomics approach to protein profiling and biomarker discovery uncovers biomarkers from a different viewpoint than microarray analysis. This review summarizes the range of proteomics technologies employed for cancer profiling, and how they have been used to derive new classification models for human lung cancer.

Biomarkers, Tumor↗