Publications by authors named "Jesper Dahlgaard"

15 Publications

  • Page 1 of 1

A Short Mindfulness Retreat for Students to Reduce Stress and Promote Self-Compassion: Pilot Randomised Controlled Trial Exploring Both an Indoor and a Natural Outdoor Retreat Setting.

Healthcare (Basel) 2021 Jul 18;9(7). Epub 2021 Jul 18.

Department of Clinical Medicine, Aarhus University, DK-8200 Aarhus, Denmark.

Here, we developed and examined a new way of disseminating mindfulness in nature to people without meditation experience, based on the finding that mindfulness conducted in natural settings may have added benefits. We evaluated a 5-day residential programme aiming to reduce stress and improve mental health outcomes. We compared an indoor and an outdoor version of the programme to a control group in a pilot randomised controlled trial (RCT). Sixty Danish university students experiencing moderate to high levels of stress were randomised into a residential mindfulness programme indoors ( = 20), in nature ( = 22), or a control group ( = 18). Participants completed the Perceived Stress Scale and the Self-Compassion Scale (primary outcomes) along with additional secondary outcome measures at the start and end of the program and 3 months after. Stress was decreased with small to medium effect sizes post-intervention, although not statistically significant. Self-compassion increased post-intervention, but effect sizes were small and not significant. At follow-up, changes in stress were not significant, however self-compassion increased for both interventions with medium-sized effects. For the intervention groups, medium- to large-sized positive effects on trait mindfulness after a behavioural task were found post-intervention, and small- to medium-sized effects in self-reported mindfulness were seen at follow-up. Connectedness to Nature was the only outcome measure with an incremental effect in nature, exceeding the control with a medium-sized effect at follow-up. All participants in the nature arm completed the intervention, and so did 97% of the participants in all three arms. Overall, the results encourage the conduct of a larger-scale RCT, but only after adjusting some elements of the programme to better fit and take advantage of the potential benefits of the natural environment.
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http://dx.doi.org/10.3390/healthcare9070910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307600PMC
July 2021

A Systematic Review and Meta-Analysis of Nature-Based Mindfulness: Effects of Moving Mindfulness Training into an Outdoor Natural Setting.

Int J Environ Res Public Health 2019 09 2;16(17). Epub 2019 Sep 2.

Department of Psychology and Behavioural Sciences, Aarhus University, C 8000 Aarhus, Denmark.

Research has proven that both mindfulness training and exposure to nature have positive health effects. The purpose of this study was to systematically review quantitative studies of mindfulness interventions conducted in nature (nature-based mindfulness), and to analyze the effects through meta-analyses. Electronic searches revealed a total of 25 studies to be included, examining 2990 participants. Three analyses were conducted: Nature-based mindfulness interventions evaluated as open trials (k = 13), nature-based mindfulness compared with groups in non-active control conditions (k = 5), and nature-based mindfulness compared with similar interventions but without contact with nature (k = 7). The overall combined psychological, physiological, and interpersonal effects from pre- to post-intervention were statistically significant and of medium size ( = 0.54, < .001). Moderation analyses showed that natural environments characterized as forests/wild nature obtained larger numerical effects than environments characterized as gardens/parks, as did informal mindfulness compared with formal mindfulness. The small number of studies included, as well as the heterogeneity and generally low quality of the studies, must be taken into consideration when the results are interpreted. PROSPERO registration number: CRD42017065639.
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http://dx.doi.org/10.3390/ijerph16173202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747393PMC
September 2019

[Psychological, neurological and cell-mediated mechanisms by mindfulness-based therapy].

Ugeskr Laeger 2019 Jul;181(30)

In this review, we present clinical studies on mindfulness-based therapy (MBT) with a focus on mediating mechanisms for its health promoting effects. These constitute awareness, self-compassion, regulation of dysfunctional patterns of thoughts and emotions, neural network and cellular processes. Among cellular processes are inflammation, oxidative stress, mitochondrial dysfunction and telomere shortening, which all contribute to the molecular pathophysiology of several of today's lifestyle diseases. Finally, we address applications, where strong evidence exists for the clinical impact of MBT.
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July 2019

Internet-Delivered Cognitive-Behavioral Therapy for Insomnia in Breast Cancer Survivors: A Randomized Controlled Trial.

J Natl Cancer Inst 2018 08;110(8):880-887

Center for Behavioral Health and Technology, Department of Psychiatry and Neurobehavioral Sciences, University of Virginia School of Medicine, Charlottesville, VA.

Background: Insomnia is two to three times more prevalent in cancer survivors than in the general population, where it is estimated to be 10% to 20%. Cognitive-behavioral therapy for insomnia (CBT-I) is the recommended treatment for chronic insomnia, but meeting survivor needs remains a challenge. Internet-delivered CBT-I (iCBT-I) has been shown efficacious in otherwise healthy adults. We tested the efficacy of iCBT-I in breast cancer survivors with clinically significant sleep disturbance.

Methods: Women from a national sample of Danish breast cancer survivors who experienced clinically significant sleep disturbance were randomly allocated to iCBT-I or waitlist control (55:45). The fully automated iCBT-I program consisted of six cores. Online measures of insomnia severity, sleep quality, and fatigue were collected at baseline, postintervention (nine weeks), and follow-up (15 weeks). Online sleep diaries were completed over two-week periods pre- and postintervention. Intention-to-treat analyses (time × group interactions) were conducted with mixed linear models and corrected for multiple outcomes. All statistical tests were two-sided.

Results: A total of 255 women were randomly allocated to iCBT-I (n = 133) or waitlist control (n = 122). Statistically significant (P ≤ .02) time × group interactions were found for all sleep-related outcomes from pre- to postintervention. Effect sizes (Cohen's d) ranged from 0.33 (95% confidence interval [CI] = 0.06 to 0.61) for wake after sleep onset to 1.17 (95% CI = 0.87 to 1.47) for insomnia severity. Improvements were maintained for outcomes measured at follow-up (d = 0.66-1.10).

Conclusions: iCBT-I appears to be effective in breast cancer survivors, with additional benefit in terms of reduced fatigue. This low-cost treatment could be incorporated in cancer rehabilitation programs.
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http://dx.doi.org/10.1093/jnci/djx293DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6093474PMC
August 2018

Clinical Impact of a Novel MicroRNA Chemo-Sensitivity Predictor in Gastrooesophageal Cancer.

PLoS One 2016 17;11(2):e0148070. Epub 2016 Feb 17.

Dept. of Oncology, Aarhus University Hospital, Aarhus, Denmark.

Background: miRNAs might be potentially useful biomarkers for prediction of response to chemotherapeutic agents, radiotherapy and survival. The aim of this retrospective study was to validate miRNA response predictors in a cohort of patients with gastrooesophageal cancer in order to predict overall survival (OS) and disease-specific survival (DSS).

Material And Methods: The study population encompassed 53 patients treated with curative intend for loco-regional gastrooesophageal cancer. miRNA expression was quantified from pre-therapeutic and diagnostic, formalin-fixed, paraffin embedded tumour specimens using Affymetrix GeneChip miRNA 1.0 Array. Based on growth inhibition of the NCI60 panel in the presence of cisplatin, epirubicine and capecitabine, a miRNA based response predictor was developed. The Cox proportional hazards model was applied to assess the correlations of the response predictor with OS and DSS.

Results: A univariate analysis demonstrated a statistical significant improvement of OS for patients who had undergone surgical resection with prediction scores above the median prediction score (HR: 0.41 (95% CI: 0.17-0.96). Adjusting for surgery and stage, this predictor was identified to be independently associated with both OS (HR: 0.37 (95% CI: 0.16-0.87)) and DSS (HR: 0.32 (0.12-0.87)).

Conclusion: The miRNA profile predictive for sensitivity to cisplatin, epirubicine and capecitabine was shown to be independently associated with OS and DSS in patients with gastrooesophageal cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148070PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757421PMC
July 2016

A systematic review of mechanisms of change in mindfulness-based cognitive therapy in the treatment of recurrent major depressive disorder.

Clin Psychol Rev 2015 Apr 11;37:26-39. Epub 2015 Feb 11.

Danish Center for Mindfulness at the Research Clinic for Functional Disorders and Psychosomatics, Aarhus University Hospital, Aarhus, Denmark.

Background: The investigation of treatment mechanisms in randomized controlled trials has considerable clinical and theoretical relevance. Despite the empirical support for the effect of mindfulness-based cognitive therapy (MBCT) in the treatment of recurrent major depressive disorder (MDD), the specific mechanisms by which MBCT leads to therapeutic change remain unclear.

Objective: By means of a systematic review we evaluate how the field is progressing in its empirical investigation of mechanisms of change in MBCT for recurrent MDD.

Method: To identify relevant studies, a systematic search was conducted. Studies were coded and ranked for quality.

Results: The search produced 476 articles, of which 23 were included. In line with the theoretical premise, 12 studies found that alterations in mindfulness, rumination, worry, compassion, or meta-awareness were associated with, predicted or mediated MBCT's effect on treatment outcome. In addition, preliminary studies indicated that alterations in attention, memory specificity, self-discrepancy, emotional reactivity and momentary positive and negative affect might play a role in how MBCT exerts its clinical effects.

Conclusion: The results suggest that MBCT could work through some of the MBCT model's theoretically predicted mechanisms. However, there is a need for more rigorous designs that can assess greater levels of causal specificity.
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http://dx.doi.org/10.1016/j.cpr.2015.02.001DOI Listing
April 2015

Development and blind clinical validation of a microRNA based predictor of response to treatment with R-CHO(E)P in DLBCL.

PLoS One 2015 18;10(2):e0115538. Epub 2015 Feb 18.

Rigshospitalet, Department of Hematology, Copenhagen, Denmark.

MicroRNAs (miRNA) are a group of short noncoding RNAs that regulate gene expression at the posttranscriptional level. It has been shown that microRNAs are independent predictors of outcome in patients with diffuse large B-cell lymphoma (DLBCL) treated with the drug combination R-CHOP. Based on the measured growth inhibition of 60 human cancer cell lines (NCI60) in the presence of doxorubicine, cyclophosphamide, vincristine and etoposide as well as the baseline microRNA expression of the 60 cell lines, a microRNA based response predictor to CHOP was developed. The response predictor consisting of 20 microRNAs was blindly validated in a cohort of 116 de novo DLBCL patients treated with R-CHOP or R-CHOEP as first line treatment. The predicted sensitivity based on diagnostic FFPE samples matched the clinical response, with decreasing sensitivity in poor responders (P = 0.03). When the International Prognostic Index (IPI) was included in the prediction analysis, the separation between responders and non-responders improved (P = 0.001). Thirteen patients developed relapse, and five patients predicted sensitive to their second and third line treatment survived a median 1194 days, while eight patients predicted not sensitive to their second and third line treatment survived a median 187 days (90% CI: 485 days versus 227 days). Among the latter group it was predicted that four would have been sensitive to another second line treatment than the one they received. The predictions were almost the same when diagnostic biopsies were used as when relapse biopsies were used. These preliminary findings warrant testing in a larger cohort of relapse patients to confirm whether the miRNA based predictor can select the optimal second line treatment and increase survival.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0115538PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4333339PMC
December 2015

Expression of microRNAs in the NCI-60 cancer cell-lines.

PLoS One 2012 28;7(11):e49918. Epub 2012 Nov 28.

Department of Thoracic Surgery, Roswell Park Cancer Institute, Buffalo, NY, USA.

The NCI-60 panel of 60 human cancer cell-lines of nine different tissues of origin has been extensively characterized in biological, molecular and pharmacological studies. Analyses of data from such studies have provided valuable information for understanding cellular processes and developing strategies for the diagnosis and treatment of cancer. Here, Affymetrix® GeneChip™ miRNA version 1 oligonucleotide microarrays were used to quantify 847 microRNAs to generate an expression dataset of 495 (58.4%) microRNAs that were identified as expressed in at least one cell-line of the NCI-60 panel. Accuracy of the microRNA measurements was partly confirmed by reverse transcription and polymerase chain reaction assays. Similar to that seen among the four existing NCI-60 microRNA datasets, the concordance of the new expression dataset with the other four was modest, with mean Pearson correlation coefficients of 0.37-0.54. In spite of this, comparable results with different datasets were noted in clustering of the cell-lines by their microRNA expression, differential expression of microRNAs by the lines' tissue of origin, and correlation of specific microRNAs with the doubling-time of cells or their radiation sensitivity. Mutation status of the cell-lines for the TP53, PTEN and BRAF but not CDKN2A or KRAS cancer-related genes was found to be associated with changes in expression of specific microRNAs. The microRNA dataset generated here should be valuable to those working in the field of microRNAs as well as in integromic studies of the NCI-60 panel.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0049918PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509128PMC
June 2013

A 71-gene signature of TRAIL sensitivity in cancer cells.

Mol Cancer Ther 2012 Jan 25;11(1):34-44. Epub 2011 Oct 25.

Division of Therapeutic Proteins, Office of Biotechnology Products, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.

TNF-related apoptosis inducing ligand (TRAIL) is a promising anticancer agent because of its ability to selectively induce apoptosis in cancer cells but not in most normal cells. However, some cancer cells are resistant to TRAIL cytotoxicity thereby limiting its therapeutic efficacy. Using genome-wide mRNA expression profiles from the NCI60 panel and their differential sensitivities to TRAIL-induced apoptosis, we have identified 71 genes whose expression levels are systemically higher in TRAIL-sensitive cell lines than resistant lines. The elevated expression of the 71 genes was able to accurately predict TRAIL sensitivity in the NCI60 training set and two test sets consisting of a total of 95 human cancer cell lines. Interestingly, the 71-gene signature is dominated by two functionally related gene families-interferon (IFN)-induced genes and the MHC genes. Consistent with this result, treatment with IFN-γ augmented TRAIL-induced apoptosis. The 71-gene signature could be evaluated clinically for predicting tumor response to TRAIL-related therapies.
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http://dx.doi.org/10.1158/1535-7163.MCT-11-0620DOI Listing
January 2012

Analytical variables influencing the performance of a miRNA based laboratory assay for prediction of relapse in stage I non-small cell lung cancer (NSCLC).

BMC Res Notes 2011 Oct 19;4:424. Epub 2011 Oct 19.

Medical Prognosis Institute, Venlighedsvej 1, 2970 Hørsholm, Denmark.

Background: Laboratory assays are needed for early stage non-small lung cancer (NSCLC) that can link molecular and clinical heterogeneity to predict relapse after surgical resection. We technically validated two miRNA assays for prediction of relapse in NSCLC. Total RNA from seventy-five formalin-fixed and paraffin-embedded (FFPE) specimens was extracted, labeled and hybridized to Affymetrix miRNA arrays using different RNA input amounts, ATP-mix dilutions, array lots and RNA extraction- and labeling methods in a total of 166 hybridizations. Two combinations of RNA extraction- and labeling methods (assays I and II) were applied to a cohort of 68 early stage NSCLC patients.

Results: RNA input amount and RNA extraction- and labeling methods affected signal intensity and the number of detected probes and probe sets, and caused large variation, whereas different ATP-mix dilutions and array lots did not. Leave-one-out accuracies for prediction of relapse were 63% and 73% for the two assays. Prognosticator calls ("no recurrence" or "recurrence") were consistent, independent on RNA amount, ATP-mix dilution, array lots and RNA extraction method. The calls were not robust to changes in labeling method.

Conclusions: In this study, we demonstrate that some analytical conditions such as RNA extraction- and labeling methods are important for the variation in assay performance whereas others are not. Thus, careful optimization that address all analytical steps and variables can improve the accuracy of prediction and facilitate the introduction of microRNA arrays in the clinic for prediction of relapse in stage I non-small cell lung cancer (NSCLC).
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http://dx.doi.org/10.1186/1756-0500-4-424DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3221722PMC
October 2011

Arrayed primer extension in the "array of arrays" format: a rational approach for microarray-based SNP genotyping.

Genet Test 2007 ;11(2):160-6

Department of Biochemistry, Pharmacology and Genetics, Human MicrroArray Centre, Odense University Hospital, Odense, DK-5000 Odense C, Denmark.

This study provides a new version of the arrayed primer extension (APEX) protocol adapted to the 'array of arrays' platform using an instrumental setup for microarray processing not previously described. The primary aim of the study is to implement a system for rational cost-efficient genotyping where multiple singlenucleotide polymorphisms (SNPs) and individuals are genotyped on each microarray slide. Genotyping results are collected across 185 healthy Danish subjects and 76 SNPs on chromosome 3q13.31, because linkage to atopic disease phenotypes have been suggested in the Danish population. Linkage disequilibrium (LD) results from the experimental data are used in a novel comparison to baseline data defined by the international HapMap SNP database. Comparison on the LD results reveals a strong linear correlation irrespective of LD measure considered: R2 (D') = 0.73 and R2(r2) = 0.54. In conclusion, our results show that this setup is strong enough to support high-throughput genotyping, and these observations support that the HapMap genotype resource is important for defining SNP panels aimed at gene mapping in local subpopulations from Europe.
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http://dx.doi.org/10.1089/gte.2007.9998DOI Listing
September 2007

dlk1/FA1 regulates the function of human bone marrow mesenchymal stem cells by modulating gene expression of pro-inflammatory cytokines and immune response-related factors.

J Biol Chem 2007 Mar 19;282(10):7339-51. Epub 2006 Dec 19.

KMEB Laboratory, Medical Biotechnology Center, Odense University Hospital, Southern Denmark University, DK-5000 Odense, Denmark.

dlk1/FA1 (delta-like 1/fetal antigen-1) is a member of the epidermal growth factor-like homeotic protein family whose expression is known to modulate the differentiation signals of mesenchymal and hematopoietic stem cells in bone marrow. We have demonstrated previously that Dlk1 can maintain the human bone marrow mesenchymal stem cells (hMSC) in an undifferentiated state. To identify the molecular mechanisms underlying these effects, we compared the basal gene expression pattern in Dlk1-overexpressing hMSC cells (hMSC-dlk1) versus control hMSC (negative for Dlk1 expression) by using Affymetrix HG-U133A microarrays. In response to Dlk1 expression, 128 genes were significantly up-regulated (with >2-fold; p < 0.001), and 24% of these genes were annotated as immune response-related factors, including pro-inflammatory cytokines, in addition to factors involved in the complement system, apoptosis, and cell adhesion. Also, addition of purified FA1 to hMSC up-regulated the same factors in a dose-dependent manner. As biological consequences of up-regulating these immune response-related factors, we showed that the inhibitory effects of dlk1 on osteoblast and adipocyte differentiation of hMSC are associated with Dlk1-induced cytokine expression. Furthermore, Dlk1 promoted B cell proliferation, synergized the immune response effects of the bacterial endotoxin lipopolysaccharide on hMSC, and led to marked transactivation of the NF-kappaB. Our data suggest a new role for Dlk1 in regulating the multiple biological functions of hMSC by influencing the composition of their microenvironment "niche." Our findings also demonstrate a role for Dlk1 in mediating the immune response.
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http://dx.doi.org/10.1074/jbc.M607530200DOI Listing
March 2007

RNA quality and gene expression analysis of ovarian tumor tissue undergoing repeated thaw-freezing.

Exp Mol Pathol 2007 Feb 13;82(1):95-102. Epub 2006 Jul 13.

Department of Obstetrics and Gynecology, Sdr. Boulevard 29, DK-5000 Odense C, Denmark.

Gene expression profiles evaluated by microarray-based quantization of RNA are used in studies of differential diagnosis and prognosis in cancer. RNA of good quality is mandatory for this evaluation. The RNA most often comes from tumor banks with limited amount of tissue, and the tissue often undergoes repeated thawing and freezing. We evaluated the influence of repeated division of tumor samples at room temperature, on RNA quality and quantity, in addition to the gene expression profile. Sixteen ovarian tumor samples were divided in three aliquots each, undergoing respectively one, two, and three thaw-freeze cycles. RNA from each aliquot was extracted on the day of division, and quantity and quality were evaluated. RNA from all three aliquots of four tumor samples underwent microarray analysis on Affymetrix Human Genome U133A 2.0 arrays. Microarray data were evaluated using both unsupervised, and supervised multivariate statistical methods, reliability analysis, as well as verification using published gene lists in ovarian cancer studies. RNA quality and quantity did not change during the division procedure and microarray data showed insignificant difference in gene expression. Tumor samples from tumor banks can be frozen and thawed at least three times without compromising the RNA integrity and genetic expression profile.
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http://dx.doi.org/10.1016/j.yexmp.2006.05.004DOI Listing
February 2007

Spotting and validation of a genome wide oligonucleotide chip with duplicate measurement of each gene.

Biochem Biophys Res Commun 2006 Jun 19;344(4):1111-20. Epub 2006 Apr 19.

Department of Biochemistry, Pharmacology, and Genetics, Odense University Hospital and Human Microarray Centre, University of Southern Denmark, Odense, Denmark.

The quality of DNA microarray based gene expression data relies on the reproducibility of several steps in a microarray experiment. We have developed a spotted genome wide microarray chip with oligonucleotides printed in duplicate in order to minimise undesirable biases, thereby optimising detection of true differential expression. The validation study design consisted of an assessment of the microarray chip performance using the MessageAmp and FairPlay labelling kits. Intraclass correlation coefficient (ICC) was used to demonstrate that MessageAmp was significantly more reproducible than FairPlay. Further examinations with MessageAmp revealed the applicability of the system. The linear range of the chips was three orders of magnitude, the precision was high, as 95% of measurements deviated less than 1.24-fold from the expected value, and the coefficient of variation for relative expression was 13.6%. Relative quantitation was more reproducible than absolute quantitation and substantial reduction of variance was attained with duplicate spotting. An analysis of variance (ANOVA) demonstrated no significant day-to-day variation.
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http://dx.doi.org/10.1016/j.bbrc.2006.03.227DOI Listing
June 2006

Genetic dissection of gene expression observed in whole blood samples of elderly Danish twins.

Hum Genet 2005 Jul 20;117(2-3):267-74. Epub 2005 May 20.

Department of Clinical Biochemistry and Genetics (KKA), Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark.

The microarray technique is an important tool in gene expression analysis to study the activities of thousands of genes measured by their transcript levels under disease or laboratory controlled experimental conditions. Recent studies have suggested a genetic component in the variations of gene expression thus indicating the important role of genetic control over gene activities. In this study, we analyze and report the twin correlation on gene expression in whole blood samples of six female Danish twin pairs aged from 81 to 85 years. We studied the expression phenotype by treating the measured gene expression as a quantitative trait and introducing analytical approaches including the traditional twin methods in population genetics and the multivariate statistical methods. Using this combinatory approach, we were able to estimate and compare the twin correlation on the expression phenotype while accounting for systematic influence in microarray experiments. Analyses on our twin data detected a significant correlation on the expression levels of the actively regulated genes in both monozygotic and dizygotic twins, which is more pronounced in monozygotic twins. Gene ontology analysis has shown that these actively regulated genes are predominantly involved in defense and immune responses against antigenic stimulus. In conclusion, the correlation patterns revealed in our twin data provide evidence of the existence of a heritable mechanism in gene expression regulation persistently functioning even in aged subjects.
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http://dx.doi.org/10.1007/s00439-005-1308-xDOI Listing
July 2005
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