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Genetic Aspects (genetic + aspect)
Selected AbstractsGenetic aspects of pathological gambling: a complex disorder with shared genetic vulnerabilitiesADDICTION, Issue 9 2009Daniela S. S. Lobo ABSTRACT Aims To summarize and discuss findings from genetic studies conducted on pathological gambling (PG). Methods Searches were conducted on PubMed and PsychInfo databases using the keywords: ,gambling and genes', ,gambling and family' and ,gambling and genetics', yielding 18 original research articles investigating the genetics of PG. Results Twin studies using the Vietnam Era Twin Registry have found that: (i) the heritability of PG is estimated to be 50,60%; (ii) PG and subclinical PG are a continuum of the same disorder; (iii) PG shares genetic vulnerability factors with antisocial behaviours, alcohol dependence and major depressive disorder; (iv) genetic factors underlie the association between exposure to traumatic life-events and PG. Molecular genetic investigations on PG are at an early stage and published studies have reported associations with genes involved in the brain's reward and impulse control systems. Conclusions Despite the paucity of studies in this area, published studies have provided considerable evidence of the influence of genetic factors on PG and its complex interaction with other psychiatric disorders and environmental factors. The next step would be to investigate the association and interaction of these variables in larger molecular genetic studies with subphenotypes that underlie PG. Results from family and genetic investigations corroborate further the importance of understanding the biological underpinnings of PG in the development of more specific treatment and prevention strategies. [source] Genetic aspects of the Paget's disease of bone: concerns on the introduction of DNA-based tests in the clinical practice.EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2010Advantages, disadvantages of its application Eur J Clin Invest 2010; 40 (7): 655,667 Abstract Background, A large amount of genetic studies have clearly demonstrated the existence of a genetic susceptibility to Paget's disease of bone (PDB). Although the disease is genetically heterogeneous, the SQSTM1/p62 gene, encoding a protein with a pathophysiological role in both osteoclast differentiation and activity, has been found worldwide to harbour germline mutations in most of the PDB patients from geographically distant populations originating from different areas of Europe, both in sporadic and familial cases. Materials and Methods, Thus, SQSTM1/p62 gene mutations may confer an increased lifetime risk of developing PDB. Results, Several different genotype-phenotype analyses have shown a high penetrance for such mutations. These results suggest the opportunity to perform genetic testing in affected individuals and then, after the identification of a SQSTM1/p62 gene germline mutation, in their relatives as a real and concrete strategy to increase the diagnostic sensitivity in most of the asymptomatic mutant carriers. However, it is of note to underlie that an incomplete penetrance for SQSTM1/p62 gene mutations has also been reported. Conclusions, In light of all these contradictory evidences, a review on whether, when and why apply the DNA test to those subjects, its interpretation and clinical application is necessary. In fact, a growing number of preventive care options are now available to affected patients and families and the process of systematically assessing risk is becoming increasingly important for both patients and physicians. [source] Genetic aspects concerning drip loss and water-holding capacity of porcine meatJOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 2007D. G. J. Jennen Summary The amount and distribution of water inside the meat has a considerable influence on its properties. High losses of fluid in the form of drip may affect financial output, nutritional value, consumer appeal and/or technological properties of porcine meat. Therefore, a deeper insight into the traits water-holding capacity (WHC) and drip is favourable on behalf of producers, industry and consumers. Similar to most meat quality traits, WHC and drip loss (DRIP) are moderately heritable. The genetic correlation between these two traits is high. Correlation to other meat quality traits, such as pH value, cooking loss, reflectance, etc. is existent as predictable. Two major genes are known, RYR1 on chromosome 6 and RN on chromosome 15, to influence meat quality in general and WHC in particular. Furthermore, a number of candidate genes exist, e.g. phosphoglycerate mutase 2. Within the variety of quantitative trait loci (QTL) experiments, a number of QTL have been identified. QTL for DRIP and/or WHC have been found on chromosome 1, 2, 4, 5, 6, 11, 13, 14, 15, 18; for cooking loss on 7, 14 and18, and for pH value on nearly all chromosomes. Recently, a QTL study for meat quality and body composition traits in a Duroc,Pietrain (DUPI) resource population has been conducted at the University of Bonn, Germany. Four QTL for DRIP were identified on chromosomes 2, 3, 5 and 18. The QTL regions are in agreement with previously published QTL for this and other related traits. Further research and finemapping has begun and candidate genes located within the QTL regions are currently under investigation. Combination and comparison of results should lead to deeper insights in the genetic background of meat quality and DRIP. [source] Hippocampal gene expression profiling across eight mouse inbred strains: towards understanding the molecular basis for behaviourEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2004Cathy Fernandes Abstract Mouse inbred strains differ in many aspects of their phenotypes, and it is known that gene expression does so too. This gives us an opportunity to isolate the genetic aspect of variation in expression and compare it to other phenotypic variables. We have investigated these issues using an eight-strain expression profile comparison with four replicates per strain on Affymetrix MGU74av2 GeneChips focusing on one well-defined brain tissue (the hippocampus). We identified substantial strain-specific variation in hippocampal gene expression, with more than two hundred genes showing strain differences by a very conservative criterion. Many such genetically driven differences in gene expression are likely to result in functional differences including differences in behaviour. A large panel of inbred strains could be used to identify genes functionally involved in particular phenotypes, similar to genetic correlation. The genetic correlation between expression profiles and function is potentially very powerful, especially given the current large-scale generation of phenotypic data on multiple strains (the Mouse Phenome Project). As an example, the strongest genetic correlation between more than 200 probe sets showing significant differences among our eight inbred strains and a ranking of these strains by aggression phenotype was found for Comt, a gene known to be involved in aggression. [source] Recent advances in the molecular pathology of soft tissue sarcoma: Implications for diagnosis, patient prognosis, and molecular target therapy in the futureCANCER SCIENCE, Issue 2 2009Yoshinao Oda In the present paper, recent advances in the molecular pathology of soft tissue sarcomas (STS) and the implications for their prognostic value are reviewed, and the potential targets of molecular therapy are discussed. According to the molecular genetic aspect, STS are divided into two groups: chromosome translocation-associated sarcomas and sarcomas without specific translocation. In the former group, specific fusion transcripts, such as SS18,SSX, EWS,FLI1, and PAX3,FKHR, could be detected in synovial sarcoma, Ewing's sarcoma and primitive neuroectodermal tumor, and alveolar rhabdomyosarcoma, respectively. The direct or indirect interactions between these fusion transcripts and cell cycle regulators have been elucidated by several investigators. Therefore, these fusion transcripts are promising candidates as molecular targets. As evaluated in carcinomas, alterations of several tumor-suppressor genes and adhesion molecules and overexpression of growth factors and their receptors have been extensively assessed in STS. In mixed-type STS, epidermal growth factor receptor overexpression was associated with decreased overall survival, suggesting the beneficial role of epidermal growth factor receptor inhibitors in STS. In malignant rhabdoid tumor and epithelioid sarcoma, frequent alteration of the SMARCB1/INI1tumor-suppressor gene and the loss of its protein have been demonstrated, indicating that this molecule could be an effective target of these sarcomas. In sarcomas with epithelioid differentiation, such as synovial sarcoma and epithelioid sarcoma, overexpression of dysadherin, which downregulates E-cadherin expression, was a poor prognostic factor. In conclusion, further studies are necessary to search for effective and specific molecules for the inhibition of tumor growth in each type of STS, especially in sarcomas without specific translocation. (Cancer Sci 2009; 100: 200,208) [source] Establishment, characterization and drug sensitivity testing in primary cultures of human thymoma and thymic carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 12 2008Volker Ehemann Abstract Thymomas and thymic carcinomas are peculiar epithelial tumors of the anterior mediastinum. They may show aggressive clinical behavior and are a paradigm for the interaction between the tumor and the immune system. So far, adequate functional studies enabling a better understanding of this malignancy have not been performed, since human thymoma/thymic carcinoma cell lines have not been available. Here, the authors describe the establishment, characterization and functional analyses of epithelial cell lines from a Type B1-thymoma and a poorly differentiated thymic carcinoma. By Fluorescence-activated cell sorting (FACS) analyses, both cell lines were aneuploid. The aneuploid cell fraction of the thymic carcinoma cell line was characterized by a high proliferation index of 55.9%, in contrast to a lower proliferation rate of the aneuploid cell fraction of the thymoma (19.7%). Array-based comparative genomic hybridization (aCGH) and conventional cytogenetic analysis of the thymoma revealed only minor imbalances whereas the thymic carcinoma was characterized by a complex karyotype in the hyperdiploid range that was readily defined with multicolor FISH (mFISH). Application of a selective COX-2 inhibitor reduced cell viability in both cell lines in a dose-dependent manner. In conclusion, these first cell lines of a thymoma and a CD5-positive thymic carcinoma are useful tools for further in vitro studies of cellular, molecular and genetic aspects of the disease and for functional tests to evaluate new therapeutic targets. © 2008 Wiley-Liss, Inc. [source] Information discovery from complementary literatures: Categorizing viruses as potential weaponsJOURNAL OF THE AMERICAN SOCIETY FOR INFORMATION SCIENCE AND TECHNOLOGY, Issue 10 2001Don R. Swanson Using novel informatics techniques to process the output of Medline searches, we have generated a list of viruses that may have the potential for development as weapons. Our findings are intended as a guide to the virus literature to support further studies that might then lead to appropriate defense and public health measures. This article stresses methods that are more generally relevant to information science. Initial Medline searches identified two kinds of virus literatures,the first concerning the genetic aspects of virulence, and the second concerning the transmission of viral diseases. Both literatures taken together are of central importance in identifying research relevant to the development of biological weapons. Yet, the two literatures had very few articles in common. We downloaded the Medline records for each of the two literatures and used a computer to extract all virus terms common to both. The fact that the resulting virus list includes most of an earlier independently published list of viruses considered by military experts to have the highest threat as potential biological weapons served as a test of the method; the test outcome showed a high degree of statistical significance, thus supporting an inference that the new viruses on the list share certain important characteristics with viruses of known biological warfare interest. [source] Myoclonus-dystonia: An update,MOVEMENT DISORDERS, Issue 4 2009Kiyoka Kinugawa MD Abstract Our knowledge of the clinical, neurophysiological, and genetic aspects of myoclonus-dystonia (M-D) has improved markedly in the recent years. Basic research has provided new insights into the complex dysfunctions involved in the pathogenesis of M-D. On the basis of a comprehensive literature search, this review summarizes current knowledge on M-D, with a focus on recent findings. We also propose modified diagnostic criteria and recommendationsfor clinical management. © 2008 Movement Disorder Society [source] Clinical and genetic aspects of distal myopathiesMUSCLE AND NERVE, Issue 11 2001David S. Saperstein MD Abstract Although most muscle disorders produce proximal weakness, some myopathies may manifest predominantly or exclusively distal weakness. Although several congenital, inflammatory, or metabolic myopathies may produce mainly distal weakness, there are several distinct entities, typically referred to as distal myopathies. Most of these are inherited conditions. The distal myopathies are rare, but characteristic clinical and histological features aid in their identification. Advances in molecular genetics have led to the identification of the gene lesions responsible for several of these entities and have also expanded our understanding of the genetic relationships of distal myopathies to other inherited disorders of muscle. This review summarizes current knowledge of the clinical and molecular aspects of the distal myopathies. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 1440,1450, 2001 [source] Bisphosphonate-related osteonecrosis: genetic and acquired risk factorsORAL DISEASES, Issue 6 2009ME Sarasquete The objectives of this study were to review epidemiological, clinical and biological aspects associated with the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in multiple myeloma (MM) patients, with special emphasis on the genetic aspects. A detailed review of previously described risk factors as well as recent genetic findings mostly comprises this work. The most recent meeting abstracts and relevant articles published in journals covered by the Science Citation Index and Medline are also examined. The review pays special attention to the genetic component of BRONJ. A total of 15 series and 14 guidelines or revisions were selected to fit the aims of the review. Gene variability was reviewed in depth to give a clinical illustration on the genetic aspects of BRONJ. Crude prevalence and 5-year cumulative incidence were considered as the most important end points for predictive purposes. Several acquired factors were recognized as predictors for BRONJ in MM, especially intravenous bisphosphonates, dental trauma and advanced age. Among genetic factors, polymorphisms on CYP2C8 gene arise as a promising risk factor. Bisphosphonate-related osteonecrosis of the jaw can be predicted with a conjunction of genetic and environmental risk factors. [source] Molecular and genetic aspects of plant responses to osmotic stressPLANT CELL & ENVIRONMENT, Issue 2 2002L. Xiong Abstract Drought, high salinity and freezing impose osmotic stress on plants. Plants respond to the stress in part by modulating gene expression, which eventually leads to the restoration of cellular homeostasis, detoxification of toxins and recovery of growth. The signal transduction pathways mediating these adaptations can be dissected by combining forward and reverse genetic approaches with molecular, biochemical and physiological studies. Arabidopsis is a useful genetic model system for this purpose and its relatives including the halophyte Thellungiella halophila, can serve as valuable complementary genetic model systems. [source] The Pseudomonas syringae effector protein, AvrRPS4, requires in planta processing and the KRVY domain to functionTHE PLANT JOURNAL, Issue 6 2009Kee Hoon Sohn Summary A Pseudomonas syringae pv. pisi effector protein, AvrRPS4, triggers RPS4 -dependent immunity in Arabidopsis. We characterized biochemical and genetic aspects of AvrRPS4 function. Secretion of AvrRPS4 from Pst DC3000 is type III secretion-dependent, and AvrRPS4 is processed into a smaller form in plant cells but not in bacteria or yeast. Agrobacterium -mediated transient expression analysis of N-terminally truncated AvrRPS4 mutants revealed that the C-terminal 88 amino acids are sufficient to trigger the hypersensitive response in turnip. N-terminal sequencing of the processed AvrRPS4 showed that processing occurs between G133 and G134. The processing-deficient mutant, R112L, still triggers RPS4 -dependent immunity, suggesting that the processing is not required for the AvrRPS4 avirulence function. AvrRPS4 enhances bacterial growth when delivered by Pta 6606 into Nicotiana benthamiana in which AvrRPS4 is not recognized. Transgenic expression of AvrRPS4 in the Arabidopsis rps4 mutant enhances the growth of Pst DC3000 and suppresses PTI (PAMP-triggered immunity), showing that AvrRPS4 promotes virulence in two distinct host plants. Furthermore, full virulence activity of AvrRPS4 requires both proteolytic processing and the KRVY motif at the N-terminus of processed AvrRPS4. XopO, an Xcv effector, shares the amino acids required for AvrRPS4 processing and the KRVY motif. XopO is also processed into a smaller form in N. benthamiana, similar to AvrRPS4, suggesting that a common mechanism is involved in activation of the virulence activities of both AvrRPS4 and XopO. [source] Genetic structure of a wide-spectrum chicken gene poolANIMAL GENETICS, Issue 5 2009Z. Granevitze Summary The genetic structure of 65 chicken populations was studied using 29 simple sequence repeat loci. Six main clusters which corresponded to geographical origins and histories were identified: Brown Egg Layers; predominantly Broilers; native Chinese breeds or breeds with recent Asian origin; predominantly breeds of European derivation; a small cluster containing populations with no common history and populations that had breeding history with White Leghorn. Another group of populations that shared their genome with several clusters was defined as ,Multi-clusters'. Gallus gallus gallus (Multi-clusters), one of the subspecies of the Red Jungle Fowl, which was previously suggested to be one of the ancestors of the domesticated chicken, has almost no shared loci with European and White Egg layer populations. In a further sub-clustering of the populations, discrimination between all the 65 populations was possible, and relationships between each were suggested. The genetic variation between populations was found to account for about 34% of the total genetic variation, 11% of the variation being between clusters and 23% being between populations within clusters. The suggested clusters may assist in future studies of genetic aspects of the chicken gene pool. [source] What role for genetics in the prediction of multiple sclerosis?ANNALS OF NEUROLOGY, Issue 1 2010Stephen Sawcer PhD For most of us, the foundations of our understanding of genetics were laid by considering Mendelian diseases in which familial recurrence risks are high, and mutant alleles are both necessary and sufficient. One consequence of this deterministic teaching is that our conceptualization of genetics tends to be dominated by the notion that the genetic aspects of disease are caused by rare alleles exerting large effects. Unfortunately, the preconceptions that flow from this training are frequently erroneous and misleading in the context of common traits, where familial recurrence risks are modest, and for the most part the relevant alleles are neither rare, necessary, nor sufficient. For these common traits, the genetic architecture is far more complex, with susceptibility rather than causality resulting from the combined effects of many alleles, each exerting only a modest effect on risk. None of these alleles is sufficient to cause disease on its own, and none is essential for the development of disease. Furthermore, most are carried by large sections of the population, the vast majority of which does not develop the disease. One consequence of our innate belief in the Mendelian paradigm is that we have an inherent expectation that knowledge about the genetic basis for a disease should allow genetic testing and thereby accurate risk prediction. There is an inevitable feeling that the same should be true in complex disease, but is it? ANN NEUROL 2010;67:3,10 [source] | |||||||||||||||||||||||||