Paola Sebastiani

..A set of gene-expression time series, collected to study the response of human fibroblasts to serum, is used to identify the properties of the method...

..g., dementia, hypertension, and cardiovascular disease) and may help dissect this complex phenotype into subphenotypes of healthy aging...

..The correlation between 3 signatures and 3 different life spans was replicated in the combined replication sets. The different signatures may help dissect this complex phenotype into sub-phenotypes of exceptional longevity...

..However, DBN approaches that use continuous variables, thus avoiding the information loss associated with discretization, have not yet been extensively assessed, and most of the proposed approaches have dealt with linear Gaussian models...

..Many microarray experiments produce temporal profiles in different biological conditions but common cluster techniques are not able to analyze the data conditional on the biological conditions...

..The maximum likelihood estimator of D'--a standard measure of linkage disequilibrium--is biased toward disequilibrium, and the bias is particularly evident in small samples and rare haplotypes...

..By stratifying patients by age, our results also suggest that different genes might modulate the rate of decline of HbF and the final level of HbF levels in sickle cell anemia...

..Our findings show the importance of modelling the complex dynamics of data collected for influenza surveillance, and suggest that dynamic Bayesian networks could be suitable modelling tools for developing epidemic surveillance systems...

..Additional validation, resequencing, and functional studies to understand the biology and reveal mechanisms by which candidate genes might have their effects are the future goals of this work...

..One of the challenges of the analysis of pooling-based genome wide association studies is to identify authentic associations among potentially thousands of false positive associations...

..The majority of genes found thus far to be associated with longevity primarily function in lipoprotein metabolism and insulin/IGF-1 signaling. There are likely many more genetic modifiers of human longevity that remain to be discovered...

..In this article, we will review the common approach to analysis of GWAS data and then discuss options to learn more from these data. We will use examples from our ongoing studies of sickle cell anemia and also GWAS in multigenic traits...

..rTDT is applied to a database of markers of susceptibility to Crohn's disease and it shows that only 2 of the 11 markers originally associated with the phenotype do not depend on assumptions about the missing data mechanism...

..6E-21) and in Thailand and Hong Kong subjects. Elements within the olfactory receptor gene cluster might play a regulatory role in gamma-globin gene expression...

..These findings suggest that use of the clinicogenomic model may expedite more invasive testing and definitive therapy for smokers with lung cancer and reduce invasive diagnostic procedures for individuals without lung cancer...

..Haemolysis-driven phenotypes, such as leg ulcers, could be improved by agents that reduce sickle erythrocyte density or increase NO bioavailability...

..We validated this model in a different population by predicting the occurrence of stroke in 114 individuals with 98.2% accuracy...

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..An alternative solution is genetic matching of cases and controls that requires, however, well defined population strata for appropriate selection of cases and controls...

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..Taken together, the data suggest that the functional motifs responsible for modulating F-cells and HbF levels reside within a 3 kb region in the second intron of BCL11A...

..Our findings suggest that nasal epithelial gene expression may serve as a relatively noninvasive surrogate to measure physiological responses to cigarette smoke and/or other inhaled exposures in large-scale epidemiological studies...

..15 × 10(-4)). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities...

..The severity score could serve as an estimate of overall disease severity in genotype-phenotype association studies, and the model provides an additional method to study the complex pathophysiology of sickle cell disease...

..As the limit of human life span was effectively approached with supercentenarians, compression of morbidity was generally observed...

..This result seems to provide further evidence that a severe bottleneck occurred during the founding of Europe and the conjectured "Out of Africa" event...

..The identification of irreversible effects of tobacco smoke on airway gene expression may provide insights into the causes of this elevated risk...

..We aimed to identify candidate drug targets by investigating the molecular effects of drugs that prevent retinal capillary demise in the diabetic rat...

..CONCLUSION: This study suggests that the integration of multiple data sources can significantly improve the detection accuracy of syndromic surveillance systems...

..Recent insights into HbF regulation have spurred new efforts to induce high HbF levels in sickle cell disease beyond those achievable with the current limited repertory of HbF inducers...

..This 3-bp deletion polymorphism is probably the most significant functional motif accounting for HMIP modulation of HbF in all 3 populations...

..Our results may provide insight into the pathogenesis of osteonecrosis in sickle cell disease, help identify individuals who are at high risk for osteonecrosis, and thus allow earlier and more effective therapeutic intervention...

..The continued analysis of the genomes of these and other rare individuals who have survived to extremely old ages should provide insight into the processes that contribute to the maintenance of health during extreme aging...

..Although androgen treatment increases muscle mass, the cell-intrinsic mechanisms engaged remain poorly understood...

..An altered EC phenotype elicited by SCD plasma may contribute to the pathogenesis of sickle vasoocclusion...

..Since many genetic aberrations of invasive disease are detectable in early stages, we hypothesized that miRNA expression dysregulation and the predicted changes in gene expression might also be found in early breast neoplasias...

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..Thus, JQ1 may be useful in studies of potentially novel mechanisms for transcriptional control as well as in translational efforts to identify therapeutic molecules to achieve viral eradication...

..In the future, whole genome sequencing with its promise of discovering hitherto unsuspected variants could add to our understanding of the genetic modifiers of this disease...

..The proposed method is robust, computationally efficient, and provides a powerful new approach for detecting and modeling pleiotropic disease loci...

..abstract:..

..These findings could lead to novel risk stratification, prevention, and treatment approaches...

..To determine whether the offspring of centenarians have personality characteristics that are distinct from the general population...

..They show that neurogenesis as well as vasculogenesis are predominant components of skeletal tissue formation and suggest common pathways are shared between post-natal stem cells and those seen in ESCs...

..It appears to us that this genetic component consists of many genetic modifiers each with modest effects, but as a group they can have a strong influence...

..In addition, we study the properties of the two approaches and describe how they can be generalized to include various models of inheritance...

..These findings indicate that gene expression in cytologically normal large-airway epithelial cells can serve as a lung cancer biomarker, potentially owing to a cancer-specific airway-wide response to cigarette smoke...

..Therefore, we hypothesize that for some centenarians, compression of disability rather than morbidity is a key feature for survival to old age...

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..Further evaluation of these findings may help to better understand the role of viral burden in defining cellular contribution to host immune response upon co-infection with secondary sexually transmitted pathogens...

..AVAILABILITY: The program is coded in Java, which runs on all relevant operating systems, including Windows, Mac and Unix/Linux, and is available from http://bios.ugr.es/BMapBuilder...

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