Filter and export

Publications

188 Publications visible to you, out of a total of 188
Comparison of scoring methods for the detection of causal genes with or without rare variants
Genetical Statistics and Systems Biology

Abstract (Expand)

Rare causal variants are believed to significantly contribute to the genetic basis of common diseases or quantitative traits. Appropriate statistical methods are required to discover the highest possible … number of disease-relevant variants in a genome-wide screening study. The publicly available Genetic Analysis Workshop 17 data set consists of 697 individuals and 24,487 genetic variants. It includes a simulated complex disease model with intermediate quantitative phenotypes. We compare four gene-wise scoring methods with respect to ranking of causal genes under variable allele frequency thresholds for collapsing of rare variants and considering whether or not rare variants were included. We also compare causal genes for which the ranks differ clearly between scoring methods regarding such characteristics as number and strength of causal variants. We corroborated our findings with additional simulations. We found that the maximum statistics method was superior in assigning high ranks to genes with a single strong causal variant. Hotelling’s T2 test was superior for genes with several independent causal variants. This was consistent for all phenotypes and was confirmed by single-gene analyses and additional simulations. The multivariate analysis performed similarly to Hotelling’s T2 test. The least absolute shrinkage and selection operator (LASSO) analysis was widely comparable with the maximum statistics method. We conclude that the maximum statistics method is a superior alternative to Hotelling’s T2 test if one expects only one independent causal variant per gene with a dominating effect. Such a variant could also be a supermarker derived by collapsing rare variants. Because the true nature of the genetic effect is unknown for real data, both methods need to be taken into consideration.

Authors: Markus Scholz, Holger Kirsten

Date Published: 1st Dec 2011

Publication Type: Journal article

High resolution genomic profiling and classical cytogenetics in a group of benign and atypical meningiomas
Genetical Statistics and Systems Biology

Abstract (Expand)

Meningiomas are classified as benign, atypical, or anaplastic. The majority are sporadic, solitary, and benign tumors with favorable prognoses. However, the prognosis for patients with anaplastic … meningiomas remains less favorable. High resolution genomic profiling has the capacity to provide more detailed information. Therefore, we analyzed genomic aberrations of benign and atypical meningiomas using single nucleotide polymorphism (SNP) array, combined with G-banding by trypsin using Giemsa stain (GTG banding), spectral karyotyping, and locus-specific fluorescence in situ hybridization (FISH). We confirmed frequently detected chromosomal aberrations in meningiomas and identified novel genetic events. Applying SNP array, we identified constitutional de novo loss or gain within chromosome 22 in three patients, possibly representing inherited causal events for meningioma formation. We show evidence for somatic segmental uniparental disomy in regions 4p16.1, 7q31.2, 8p23.2, and 9p22.1 not previously described for primary meningioma. GTG-banding and spectral karyotyping detected a novel balanced reciprocal translocation t(4;10)(q12;q26) in one benign meningioma. A paracentric inversion within 1p36, previously described as novel, was detected as a recurrent chromosomal aberration in benign and atypical meningiomas. Analyses of tumors and matched normal tissues with a combination of SNP arrays and complementary techniques will help to further elucidate potentially causal genetic events for tumorigenesis of meningioma.

Authors: Heidrun Holland, Kristin Mocker, Peter Ahnert, Holger Kirsten, Helene Hantmann, Ronald Koschny, Manfred Bauer, Ralf Schober, Markus Scholz, Jürgen Meixensberger, Wolfgang Krupp

Date Published: 1st Oct 2011

Publication Type: Journal article

Genetic variation in the Sorbs of eastern Germany in the context of broader European genetic diversity
Genetical Statistics and Systems Biology

Abstract (Expand)

Population isolates have long been of interest to genetic epidemiologists because of their potential to increase power to detect disease-causing genetic variants. The Sorbs of Germany are considered … as cultural and linguistic isolates and have recently been the focus of disease association mapping efforts. They are thought to have settled in their present location in eastern Germany after a westward migration from a largely Slavic-speaking territory during the Middle Ages. To examine Sorbian genetic diversity within the context of other European populations, we analyzed genotype data for over 30 000 autosomal single-nucleotide polymorphisms from over 200 Sorbs individuals. We compare the Sorbs with other European individuals, including samples from population isolates. Despite their geographical proximity to German speakers, the Sorbs showed greatest genetic similarity to Polish and Czech individuals, consistent with the linguistic proximity of Sorbian to other West Slavic languages. The Sorbs also showed evidence of subtle levels of genetic isolation in comparison with samples from non-isolated European populations. The level of genetic isolation was less than that observed for the Sardinians and French Basque, who were clear outliers on multiple measures of isolation. The finding of the Sorbs as only a minor genetic isolate demonstrates the need to genetically characterize putative population isolates, as they possess a wide range of levels of isolation because of their different demographic histories.

Authors: Krishna R. Veeramah, Anke Tönjes, Peter Kovacs, Arnd Gross, Daniel Wegmann, Patrick Geary, Daniela Gasperikova, Iwar Klimes, Markus Scholz, John Novembre, Michael Stumvoll

Date Published: 1st Sep 2011

Publication Type: Journal article

Circulating Nampt and RBP4 levels in patients with carotid stenosis undergoing carotid endarterectomy (CEA)
Genetical Statistics and Systems Biology

Abstract (Expand)

BACKGROUND\backslashr\backslashnObesity is a risk factor for atherosclerotic vascular disease. Altered adipokine secretion, including increased production of nicotinamide phosphoribosyltransferase … (Nampt) and retinol binding protein 4 (RBP4) may link adipose tissue dysfunction to cardiovascular complications.\backslashr\backslashnMETHODS\backslashr\backslashnWe determined Nampt and RBP4 serum concentrations in 193 consecutive patients with carotid stenosis prior to carotid endarterectomy (CEA) in relation to recently experienced ischemic events, markers of atherosclerosis and obesity, as well as anthropometric and clinical characteristics.\backslashr\backslashnRESULTS\backslashr\backslashnNampt but not RBP4 was significantly higher in symptomatic patients who experienced an ischemic event within 6 months before surgery compared to asymptomatic patients (p=0.001). In multivariate regression analysis Nampt was the only independent predictor of symptomatic carotid stenosis. Nampt correlated with peripheral leukocyte blood count (p\textless0.0001) and with the number of macrophages/foam cells within carotid plaques (p=0.042). However, Nampt and RBP4 serum concentrations did not correlate with the maximum percentage of carotid stenosis.\backslashr\backslashnCONCLUSION\backslashr\backslashnOur data suggest circulating Nampt as an independent predictor of recently experienced ischemic events in patients with carotid stenosis despite the lack of an association between Nampt and carotid atherosclerosis severity. BACKGROUND Obesity is a risk factor for atherosclerotic vascular disease. Altered adipokine secretion, including increased production of nicotinamide phosphoribosyltransferase (Nampt) and retinol binding protein 4 (RBP4) may link adipose tissue dysfunction to cardiovascular complications. METHODS We determined Nampt and RBP4 serum concentrations in 193 consecutive patients with carotid stenosis prior to carotid endarterectomy (CEA) in relation to recently experienced ischemic events, markers of atherosclerosis and obesity, as well as anthropometric and clinical characteristics. RESULTS Nampt but not RBP4 was significantly higher in symptomatic patients who experienced an ischemic event within 6 months before surgery compared to asymptomatic patients (p=0.001). In multivariate regression analysis Nampt was the only independent predictor of symptomatic carotid stenosis. Nampt correlated with peripheral leukocyte blood count (p\textless0.0001) and with the number of macrophages/foam cells within carotid plaques (p=0.042). However, Nampt and RBP4 serum concentrations did not correlate with the maximum percentage of carotid stenosis. CONCLUSION Our data suggest circulating Nampt as an independent predictor of recently experienced ischemic events in patients with carotid stenosis despite the lack of an association between Nampt and carotid atherosclerosis severity.

Authors: Gabriela Aust, Migle Uptaite-Patapoviene, Markus Scholz, Olaf Richter, Silvio Rohm, Matthias Blüher

Date Published: 1st Jun 2011

Publication Type: Journal article

Increased CD64 expression on polymorphonuclear neutrophils indicates infectious complications following solid organ transplantation
Genetical Statistics and Systems Biology

Abstract (Expand)

The aim of this study was to evaluate the diagnostic value of monitoring CD64 antigen upregulation on polymorphonuclear neutrophils (PMN) for the identification of infectious complications in the … postoperative course of solid organ transplanted patients. Twenty-five kidney, 13 liver, and four pancreas-kidney transplanted patients were included. Beginning with preoperative values up to postoperative values after 3 months for each patient, the PMN CD64 Index, HLA-DR on monocytes, NKp44+ NK and NK/T cells, CXCR3+ NK cells, CXCR3+ T helper cells, CXCR3+ NK/T cells, and CD4/CD8 ratio were measured by flow cytometry. Subsequently they were correlated with confirmed postoperative complications. Measuring the PMN CD64 Index reached a sensitivity of 89% and a specificity of 65% in the detection of infectious complications. Concerning this matter, it was a significantly better marker than all other included parameters except CXCR3+ NK/T cells. In contrast, according to our results the PMN CD64 Index has no diagnostic relevance in detection of rejections. The combination of included parameters showed no improved diagnostic value. Due to its high sensitivity and specificity for infectious complications CD64 on PMN could be proven a very good indicator in evaluating suspected infectious complications in the postoperative course of transplanted patients. The aim of this study was to evaluate the diagnostic value of monitoring CD64 antigen upregulation on polymorphonuclear neutrophils (PMN) for the identification of infectious complications in the postoperative course of solid organ transplanted patients. Twenty-five kidney, 13 liver, and four pancreas-kidney transplanted patients were included. Beginning with preoperative values up to postoperative values after 3 months for each patient, the PMN CD64 Index, HLA-DR on monocytes, NKp44+ NK and NK/T cells, CXCR3+ NK cells, CXCR3+ T helper cells, CXCR3+ NK/T cells, and CD4/CD8 ratio were measured by flow cytometry. Subsequently they were correlated with confirmed postoperative complications. Measuring the PMN CD64 Index reached a sensitivity of 89% and a specificity of 65% in the detection of infectious complications. Concerning this matter, it was a significantly better marker than all other included parameters except CXCR3+ NK/T cells. In contrast, according to our results the PMN CD64 Index has no diagnostic relevance in detection of rejections. The combination of included parameters showed no improved diagnostic value. Due to its high sensitivity and specificity for infectious complications CD64 on PMN could be proven a very good indicator in evaluating suspected infectious complications in the postoperative course of transplanted patients.

Authors: Daniel Grey, Ulrich Sack, Markus Scholz, Heike Knaack, Stephan Fricke, Christoph Oppel, Daniel Luderer, Josef Fangmann, Frank Emmrich, Manja Kamprad

Date Published: 1st Jun 2011

Publication Type: Journal article

Influence of low dose irradiation on differentiation, maturation and T-cell activation of human dendritic cells
Genetical Statistics and Systems Biology

Abstract (Expand)

Ionizing irradiation could act directly on immune cells and may induce bystander effects mediated by soluble factors that are released by the irradiated cells. This is the first study analyzing both … the direct effect of low dose ionizing radiation (LDIR) on the maturation and cytokine release of human dendritic cells (DCs) and the functional consequences for co-cultured T-cells. We showed that irradiation of DC-precursors in vitro does not influence surface marker expression or cytokine profile of immature DCs nor of mature DCs after LPS treatment. There was no difference of single dose irradiation versus fractionated irradiation protocols on the behavior of the mature DCs. Further, the low dose irradiation did not change the capacity of the DCs to stimulate T-cell proliferation. But the irradiation of the co-culture of DCs and T-cells revealed significantly lower proliferation of T-cells with higher doses. Summarizing the data from approx. 50 DC preparations there is no significant effect of low dose ionizing irradiation on the cytokine profile, surface marker expression and maturation of DCs in vitro although functional consequences cannot be excluded. Ionizing irradiation could act directly on immune cells and may induce bystander effects mediated by soluble factors that are released by the irradiated cells. This is the first study analyzing both the direct effect of low dose ionizing radiation (LDIR) on the maturation and cytokine release of human dendritic cells (DCs) and the functional consequences for co-cultured T-cells. We showed that irradiation of DC-precursors in vitro does not influence surface marker expression or cytokine profile of immature DCs nor of mature DCs after LPS treatment. There was no difference of single dose irradiation versus fractionated irradiation protocols on the behavior of the mature DCs. Further, the low dose irradiation did not change the capacity of the DCs to stimulate T-cell proliferation. But the irradiation of the co-culture of DCs and T-cells revealed significantly lower proliferation of T-cells with higher doses. Summarizing the data from approx. 50 DC preparations there is no significant effect of low dose ionizing irradiation on the cytokine profile, surface marker expression and maturation of DCs in vitro although functional consequences cannot be excluded.

Authors: Jutta Jahns, Ulf Anderegg, Anja Saalbach, Britt Rosin, Ina Patties, Annegret Glasow, Manja Kamprad, Markus Scholz, Guido Hildebrandt

Date Published: 1st May 2011

Publication Type: Journal article

Monitoring of WT1 expression in PB and CD34(+) donor chimerism of BM predicts early relapse in AML and MDS patients after hematopoietic cell transplantation with reduced-intensity conditioning
Genetical Statistics and Systems Biology

Abstract (Expand)

Relapse of malignant disease remains the major complication in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) after hematopoietic cell transplantation (HCT) with … reduced-intensity conditioning (RIC). In this study, we investigated the predictive value of disease-specific markers (DSMs), donor chimerism (DC) analysis of unsorted (UDC) or CD34(+) sorted cells and Wilms’ tumor gene 1 (WT1) expression. Eighty-eight patients with AML or MDS were monitored after allogenic HCT following 2 Gy total-body irradiation with (n=84) or without (n=4) fludarabine 3 \times 30 mg/m(2), followed by cyclosporin A and mycophenolate mofetil. DSMs were determined by fluorescence in situ hybridization (FISH) and WT1 expression by real-time polymerase chain reaction. Chimerism analysis was performed on unsorted or CD34(+) sorted cells, by FISH or short tandem repeat polymerase chain reaction. Twenty-one (24%) patients relapsed within 4 months after HCT. UDC, CD34(+) DC and WT1 expression were each significant predictors of relapse with sensitivities ranging from 53 to 79% and specificities of 82-91%. Relapse within 28 days was excluded almost entirely on the basis of WT1 expression combined with CD34(+) DC kinetics. Monitoring of WT1 expression and CD34(+) DC predict relapse of AML and MDS after RIC-HCT.

Authors: T. Lange, M. Hubmann, Ralph Burkhardt, G-N Franke, M. Cross, Markus Scholz, S. Leiblein, H. K. Al-Ali, J. Edelmann, Joachim Thiery, D. Niederwieser

Date Published: 1st Mar 2011

Publication Type: Journal article

Navigate

Health Atlas - Local Data Hub/Leipzig

The Health Atlas - Local Data Hub/Leipzig is an alliance of medical ontologists, medical systems biologists and clinical trials groups to design and implement a multi-functional and quality-assured atlas. It provides models, data and metadata on specific use cases from medical research fields.

Registered Repository

re3data.org Badge
Powered by
 (v.1.13.0-master)
Health Atlas | Funding and Programmes | Credits | Terms & Conditions | Privacy Policy | Imprint
Copyright © 2008 - 2021 The University of Manchester and HITS gGmbH
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig

By continuing to use this site you agree to the use of cookies