Research team

VIB CMN - Neurodegenerative Brain Diseases Group

Expertise

The VIB8 research group Applied Molecular Genetics provides its expertise to third parties. Our bioinformatics expertise enabled us to develop and offer DNA analysis software tools, SNPbox, novoSNP and MAQs. Besides our bioinformatics application we also offer genetic and genomic expertise to third parties. Among others we offer: STR based human genome scans; the isolation, identification en genotyping of STR markers and SNPs; high throughput sequencing and genotyping projects, support and development of multiplex PCR applications, construction of quantitative PCR multiplex assays.

Identification and functional characterisation of variant in microRNA genes involved in epileptic encephalopathies. 01/01/2014 - 31/12/2017

Abstract

During my PhD, I will investigate the role of microRNAs in epileptic encephalopathies. Epileptic encephalopathies are a subgroup of the epilepsies, where patients have an early age-of-onset and a poor outcome, meaning that they develop cognitive impairments and that they are refractory to anti-epileptic drugs. More and more evidence is emerging that microRNAs are involved in the pathomechanism of epilepsy. The hypothesis of my project is that variants in microRNAs can be causal for these severe epilepsies. To investigate this, I will perform a variant screening in a cohort of patients with epileptic encephalopathies, followed by extensive functional characterisation of the microRNA and the variant herein. This will lead to a better insight in the pathomechanism of epileptic encephalopathies and hopefully in the discovery of new ways to target these disorders.

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Research team(s)

Development of the BioGraph technology for valorisation in life sciences industries. 01/03/2012 - 28/02/2013

Abstract

BioGraph is a data mining technology, developed at the University of Antwerp, for unsupervised biomedical knowledge discovery via automatically generated hypotheses in integrated knowledge databases. For this technology, we study business development opportunities and develop a specific off-the-shelf application for the interpretation of microarray studies.

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Research team(s)

    Genetic and functional analysis of human brain expressed microRNA genes. 01/10/2011 - 30/09/2012

    Abstract

    MiRNAs have been implicated in a wide variety of basic cellular functions. In the brain miRNAs regulate differentiation, maturation and synaptic plasticity. This project aims to gain more insight in the involvement of miRNA genes in relation to brain functioning, by combining molecular genetics and analysis of structure and function of relevant variant miRNAs."

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      Development for large data sets and their application to non-coding genetic information involved in psychiatric diseases. 01/01/2011 - 31/12/2012

      Abstract

      This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

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      Research team(s)

        The Biomark Microfluidics system for high throughput genotyping, expression profiling and CNV analysis. 22/07/2010 - 30/09/2013

        Abstract

        The microfluidic BioMark¿ Genetic Analysis Platform from Fluidigm (www.fluidigm.com) is a fully integrated system enabling high throughput analysis of gene expression, SNP genotyping and absolute quantification of nucleic-acid sequences utilizing Digital and/or Dynamic Array Integrated Fluidic Chip (IFC) technology. Besides increasing the genetic and genomic analysis capacity the system at the same time enables significant reduction in the use of precious DNA/RNA samples and significant reduction (up to 100-fold) of consumable cost due to the nanoliter based reaction volumes (i.e. cost per datapoint).

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          Identification of genetic/genomic factors involved in giftedness. 01/01/2010 - 31/12/2013

          Abstract

          The aim of the project is to initiate and perform state of the art molecular genetics/genomics research on giftedness in children starting from the large and unique population collected by CBO. The milestones of this project are: ¿ Construction of a bio bank for giftedness research ¿ Identification of candidate genes for giftedness using a SNP based whole genome association approach ¿ Determination of the involvement of copy number variations (CNVs) in the etiology of giftedness

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            Identification of causal variants for psychiatric diseases through massive parallel resequencing methods. 01/01/2010 - 31/12/2013

            Abstract

            The aim of this project is the identification of rare and/or common risk variants that are implicated in the development of SZ and BP disorder. Hereto we will use massive parallel resequencing approaches. During this project we will obtain expertise in generating large sequencing datasets as well as expertise in the analysis of these large sequence based datasets. The milestones of the project are: ¿ Exon based candidate gene resequencing ¿ Region specific resequencing ¿ Whole human genome resequencing

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              VIB-Neurotrophic factors in the pathophysiology of depression: focus on VEGF (DEPVEGF). 01/01/2010 - 31/12/2011

              Abstract

              This project represents a research agreement between the UA and on the onther hand IWT. UA provides IWT research results mentioned in the title of the project under the conditions as stipulated in this contract.

              Researcher(s)

              Research team(s)

                Identification of susceptibility genes for psychiatric disorders through a functional genomic approach. 01/01/2009 - 31/12/2010

                Abstract

                Bipolar (BP) disorder and schizophrenia (SZ) are among the most common brain diseases worldwide and result in high social and economical costs in terms of morbidity as well as mortality. Both genetic and environmental factors play an important role in the development of BP disorder and SZ. It is supposed that both disorders result from an interaction of susceptibility genes and/or as a result of complex genetic mechanisms. The aim of this project is to understand the different mechanisms that underlie psychiatric disorders and to determine how important these mechanisms are in the patient populations. These objectives will be realized by examining three hypotheses. These three different ways of thinking all have as primary aim the identification of positional and functional candidate genes for BP disorder and/or SZ. Hypothesis 1: Identification of positional candidate genes on chromosome 6. Our research group found a strong indication for linkage on chromosome 6q23-q24 in nine northern Swedish multigenerational families. Fine-mapping of this region will be done using SNP based genotyping methods. A SNP based association study in large patient/control populations will further reduce the candidate region. Hypothesis 2: Importance of copy number variations on the susceptibility for BP and SZ. The recent literature strongly indicates that copy number variations (CNVs) might be responsible for complex disorders such as BP disorder and SZ. The published potential instable regions will be analysed in our association populations by using an in house developed method (Multiplex Amplicon Quantification MAQ). By doing this we'll gain insight in the significance of genomic instability as the underlying cause of BP disorder and SZ. Hypothesis 3: Post-transcriptional modifications as a cause of BP disorder and SZ. It is assumed that certain mechanisms, like gene regulation, are responsible for complex disorders. A-to-I RNA editing by "Adenosine Deaminases Acting on RNA" (ADAR) is a form of post-transcriptional modification, which is already described for mRNAs coding for the serotonin receptor 5-HTR2C and for the glutamate receptor GRIA2. The different ADAR-genes and target-genes that are possibly related to BP disorder and SZ will be subjected to an association study and/or mutation analysis.

                Researcher(s)

                Research team(s)

                  Development of methods for high throughput, region-specific transcriptome analysis and its application in psychiatric diseases. 01/01/2009 - 31/12/2010

                  Abstract

                  The goal of this PhD project is to develop methodologies for high throughput transcriptome analysis. The methodology will be a combination of bioinformatics and new experimental techniques and will consist of three steps. The first step is the prediction of transcripts in a genomic region. For this prediction we will combine existing and new software to create a sensitive prediction pipeline. The second step is the high throughput experimental detection of the transcripts by using the massive parallel sequencing platform GS FLX from Roche. This platform generates transcript sequences which will be annotated/analyzed in a third step.

                  Researcher(s)

                  Research team(s)

                    The development of a magnetic DNA sensor array. 01/10/2008 - 30/09/2012

                    Abstract

                    This project is the first step towards a point-of-care diagnostic device. The main goal is to develop a highly sensitive biosensor platform for the simultaneous detection and analysis of multiple nucleic acid molecules. This project is a collaborative effort between IMEC and the Applied Molecular Genomics group of the VIB Department of Molecular Genetics

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                      Identification of susceptibility genes for schizophrenia. 01/10/2008 - 30/09/2009

                      Abstract

                      The aim of this project is to perform molecular genetics research to improve our knowledge about the etiology of schizophrenia (SZ) in general and of cognitive functioning in these patient in particular. The main goal is to establish a biobank with biological material (DNA, cellines, plasma) combined with detailed fenotypic data of unrelated SZ patients. Also we will collect large multigenerational families for linkage studies. DNA from this biobank will be used for molecular genetics/genomics analyses.

                      Researcher(s)

                      Research team(s)

                        BOF - University Research Fund: 1 year doctoral fellowship in view of a second IWT application (Bart Aelterman). 01/01/2008 - 31/12/2008

                        Abstract

                        The goal of this PhD project is to develop methodologies for high throughput transcriptome analysis. The methodology will be a combination of bioinformatics and new experimental techniques and will consist of three steps. The first step is the prediction of transcripts in a genomic region. For this prediction we will combine existing and new software to create a sensitive prediction pipeline. The second step is the high throughput experimental detection of the transcripts by using the massive parallel sequencing platform GS FLX from Roche. This platform generates transcript sequences which will be annotated/analyzed in a third step.

                        Researcher(s)

                        Research team(s)

                          VIB-Genetics of highly giftedness. 01/11/2007 - 31/10/2008

                          Abstract

                          The aim of the project is to initiate molecular genetics/genomics research of giftedness in children starting from the unique population collected by CBO. The milestones of this project are: - Construction of a bio bank - Identification of candidate genes for giftedness using a SNP based whole genome association approach - Association studies for giftedness and cognition related genes - Determination the involvement of copy number variations (CNVs) in the etiology of giftedness

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                          Research team(s)

                            Text Mining on heterogeneous knowledge bases. An application to optimised discovery of disease relevant genetic variants 01/07/2007 - 30/06/2011

                            Abstract

                            The project proposes a methodology for text mining with heterogeneous information sources and its application to molecular genetics/genomics and knowledge management. State of the art text analysis and graph-based data mining techniques will be extended to make the methodology possible, and the methodology will be applied in a biomedical application (ranking of candidate disease-causing genes) and a knowledge management application (person profiling from www information).

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                            Project website

                            Valorization of isolation method for normalization and control ef emergin pathogenic escherichia coli. (STECTRACK) 01/02/2007 - 31/01/2009

                            Abstract

                            This project aims at validating a detection and isolation methodology for non-O 157 and for sorbitol-positive O157 in food products, animal related farm samples and clinical human samples. The development of this methodology and its availability in Belgium is the first and necessary step in a program for prevention of human infection due to contaminated food products.

                            Researcher(s)

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                              Molecular genetics/genomics of psychiatric diseases in an isolated population. 01/01/2007 - 31/12/2010

                              Abstract

                              Aims of the project : A. Identification of novel genes for psychiatric disorders in an isolated population from Northern Sweden B. Identification of novel loci for psychiatric disorders C. Development of neurophenomics research D. Development of genetic and genomic Multiplex PCR applications

                              Researcher(s)

                              Research team(s)

                                Identification of susceptibility genes for psychiatric disorders through a functional genomic approach. 01/01/2007 - 31/12/2008

                                Abstract

                                Bipolar (BP) disorder and schizophrenia (SZ) are among the most common brain diseases worldwide and result in high social and economical costs in terms of morbidity as well as mortality. Both genetic and environmental factors play an important role in the development of BP disorder and SZ. It is supposed that both disorders result from an interaction of susceptibility genes and/or as a result of complex genetic mechanisms. The aim of this project is to understand the different mechanisms that underlie psychiatric disorders and to determine how important these mechanisms are in the patient populations. These objectives will be realized by examining three hypotheses. These three different ways of thinking all have as primary aim the identification of positional and functional candidate genes for BP disorder and/or SZ. Hypothesis 1: Identification of positional candidate genes on chromosome 6. Our research group found a strong indication for linkage on chromosome 6q23-q24 in nine northern Swedish multigenerational families. Fine-mapping of this region will be done using SNP based genotyping methods. A SNP based association study in large patient/control populations will further reduce the candidate region. Hypothesis 2: Importance of copy number variations on the susceptibility for BP and SZ. The recent literature strongly indicates that copy number variations (CNVs) might be responsible for complex disorders such as BP disorder and SZ. The published potential instable regions will be analysed in our association populations by using an in house developed method (Multiplex Amplicon Quantification ¿ MAQ). By doing this we'll gain insight in the significance of genomic instability as the underlying cause of BP disorder and SZ. Hypothesis 3: Post-transcriptional modifications as a cause of BP disorder and SZ. It is assumed that certain mechanisms, like gene regulation, are responsible for complex disorders. A-to-I RNA editing by "Adenosine Deaminases Acting on RNA" (ADAR) is a form of post-transcriptional modification, which is already described for mRNAs coding for the serotonin receptor 5-HTR2C and for the glutamate receptor GRIA2. The different ADAR-genes and target-genes that are possibly related to BP disorder and SZ will be subjected to an association study and/or mutation analysis.

                                Researcher(s)

                                Research team(s)

                                  (Epi) genetic analysis of candidate genes for schizophrenia and bipolar disorder. 01/10/2006 - 31/12/2011

                                  Abstract

                                  This project represents a research contract awarded by the University of Antwerp. The supervisor provides the Antwerp University research mentioned in the title of the project under the conditions stipulated by the university.

                                  Researcher(s)

                                  Research team(s)

                                  Identification of susceptibility genes for affective disorders and schizophrenia. 01/10/2006 - 30/09/2008

                                  Abstract

                                  This PhD project aims to identify susceptibility genes that play a role in the etiology of the psychiatric disorders schizophrenia (SZ) and bipolar disorder (BP). Both are severe psychiatric disorders with a worldwide prevalence of about 1%. Bipolar disorder is a mood disorder characterized by the cyclic alteration of manic and depressive periods, schizophrenia is characterized by the occurrence of psychoses (periods in which contact with reality is disturbed), affective and cognitive symptoms. These are complex disorders, meaning that they are caused by an interaction of different genetic and environmental factors. Despite the high prevalence, morbidity and socio-economical costs, the pathophysiology and etiology of BP and SZ are still unknown. In this project we will use a positional cloning strategy. By performing a complete genome scan we will be able to determine chromosomal regions that show linkage with the disorders and positional candidate genes will be evaluated for their contribution to the etiology of BP and SZ through association studies. Also already known functional candidate genes will be analyzed using population based association studies. For the genome scan we have access to a unique family-based patient population from the Skellefteå region in the province of Västerbotten (northern Sweden). This Skellefteå population is a geographically isolated population, founded in 1320 and characterized by low immigration and emigration and a high expansion rate. For the association studies we have patient-control populations existing of 276 SZ patients and 500 non-related healthy controls and 276 BP patients and 500 non-related healthy controls.

                                  Researcher(s)

                                  Research team(s)

                                    VIB-Multiplex Amplicon Quantification (MAQ). 01/07/2006 - 31/12/2006

                                    Abstract

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                                    Research team(s)

                                      Molecular genetic service spin-off: Multiplex PCR algorithm in DNA profiling. 01/02/2006 - 31/12/2010

                                      Abstract

                                      This project is centered round 3 defined goals: providing non-standard fee-for-service expertise (services); technology development to create new products and/or methods (technology development); and molecular genetics research related to complex diseases in general and psychiatric diseases in particular (complex genetics). Through our services we provide third parties the possibility to use our genetic analysis expertise, like sequence based SNP discovery and genotyping STR markers and SNPs on a fee-for-service basis. To provide these genetic services we use the state of the art platform available in the Genetic Service Facility (GSF) of the VIB8-Department of Molecular Genetics (see also project ID: 20983). The goal of the technology development is to create novel products (e.g. software and diagnostic kits) and methods resulting from the expertise present in the Applied Molecular Genomics research group and is at the moment mainly focused on our proprietary multiplex PCR technology. The complex genetics research goal is focusing on the identification of susceptibility genes for schizophrenia and affective disorders through the use of family and population based genetic analysis.

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                                        VIB-The genetic basis for psychiatric diseases: a multidisciplinary approach. 01/01/2006 - 31/12/2009

                                        Abstract

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                                        Research team(s)

                                          VIB-Genetic Service Facility: Support Centralized Service Facilities. 01/01/2005 - 31/12/2017

                                          Abstract

                                          The GSF is a centralized facility within the VIB Department of Molecular Genetics (DMG) located at the University of Antwerp. The DMG GSF is subsidized by the institute VIB to provide capacity for standard Sanger sequencing services to VIB scientists at marginal costs. The DMG GSF has a competitive position because of high processing capacity and high quality service. With an optimized database system LIMS (Laboratory Information Management System), ELN (Electronic Laboratory Notebook) and GLP ("good laboratory practice") environment, the majority of the data processing is executed automatically and in optimal conditions. The DMG GSF also offers consultation and assistance upon customer's request. Years of collaboration with industrial partners resulted in a setting and a methodology where confidentiality of the data is assured. For the Sanger sequencing services, the DMG GSF is equipped with three 3730 XL 96-capillary DNA Analyzers (Life Technologies), three automated workstations (Biomek NX, Biomek NXP and Biomek FXP, Beckman Coulter) for automatic pre- and post- processing of samples, including purification, DNA whole genome amplification, aliquoting, dilution, normalization and pooling of samples. On the same platform, the VIB DMG can also provide non-standard services on a custom-basis for the analysis of mono- or multiplex STR markers, whole-genome wide STR markers or dosage analysis of CNV. The VIB DMG is also Equipped with three MiSeq and one NextSeq500 systems (Illumina) which allow NGS services including targeted, whole exome (WES) and RNA sequencing.

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                                          Research team(s)

                                          ICP Ph.D. scholarship Alice Matimba: Pharmacogenetics of genes important for drug absorption, distribution, metabolism, excretion and toxicology (ADMET) in African populations and evolutionary implications of interethnic genetic variability. 01/10/2004 - 30/09/2007

                                          Abstract

                                          In the Molecular Genetics department VIB8 the focus is on the identification of genes and/or risk factors for complex brain diseases e.g. Alzheimer's dementia, psychiatric diseases and idiopathic epilepsies. These genetic factors can be used in pharmacogenetics to define genetically more homogeneous patient groups in clinical studies of drug response and side effects. To allow rapid and efficient identification of genetic factors for complex diseases and analysing them in large samples, the department of Molecular Genetics has built a central core facility for high-throughput genetic analyses using modern genetic techniques e.g. Pyrosequencing and Sequenom for SNP analyses, capillary sequencers, robots, etc.. (see http://www.vibgeneticservicefacility.be/). In addition a bioinformatics group is active in data analysis (LIMS) by developing in-house software tools e.g. novoSNP for automatic SNP detection in sequence traces, SNPbox for automatic primer design for large throughput SNP detection or sequencing. These technology and information platforms will be important in the pharmacogenetics project aiming at analyzing genes important for drug absorption, distribution, metabolism, excretion and toxicology (ADMET) in African populations and evolutionary implications of interethnic genetic variability.

                                          Researcher(s)

                                          Research team(s)

                                          Identification of susceptibility genes for affective disorders. 01/10/2004 - 30/09/2006

                                          Abstract

                                          This PhD project aims to identify susceptibility genes that play a role in the etiology of the psychiatric disorders schizophrenia (SZ) and bipolar disorder (BP). Both are severe psychiatric disorders with a worldwide prevalence of about 1%. Bipolar disorder is a mood disorder characterized by the cyclic alteration of manic and depressive periods, schizophrenia is characterized by the occurrence of psychoses (periods in which contact with reality is disturbed), affective and cognitive symptoms. These are complex disorders, meaning that they are caused by an interaction of different genetic and environmental factors. Despite the high prevalence, morbidity and socio-economical costs, the pathophysiology and etiology of BP and SZ are still unknown. In this project we will use a positional cloning strategy. By performing a complete genome scan we will be able to determine chromosomal regions that show linkage with the disorders and positional candidate genes will be evaluated for their contribution to the etiology of BP and SZ through association studies. Also already known functional candidate genes will be analyzed using population based association studies. For the genome scan we have access to a unique family-based patient population from the Skellefteå region in the province of Västerbotten (northern Sweden). This Skellefteå population is a geographically isolated population, founded in 1320 and characterized by low immigration and emigration and a high expansion rate. For the association studies we have patient-control populations existing of 276 SZ patients and 500 non-related healthy controls and 276 BP patients and 500 non-related healthy controls.

                                          Researcher(s)

                                          Research team(s)

                                            Identification of biomarkers for affective disorder by means of suppressive subtraction hyhridisation. 01/10/2004 - 30/09/2006

                                            Abstract

                                            Bipolar disorder (BP) is a severe psychiatric condition characterised by periods of mania and depression. The infliction is devastating for patient and his surroundings, on average 10 to 20% of the patients untimely die by suicide. BP has a lifetime prevalence of 0,5 ' 1,5%. Family, twin and adoption studies have shown that BP has a significant genetic component. Several linkage and association studies identified candidate susceptibility genes and candidate loci but till now none of these yielded a true disease-causing gene. The real problem of this disorder lies within the treatment. The evaluation period for subscribed medicines for a depressive period is 4 to 6 weeks, after witch another treatment can be tested when the previous one has proven to be ineffective. In 20% of the cases no effective treatment can be found within 2 ' 3 years. Moreover the effectiveness of mood stabilizing treatment such as the treatment with lithium, carbamazepine or valproate can only be evaluated when proven ineffective, when a patient refalls into an affective disordered condition. The goals of the proposed research is to discover biomarkers for BP, which can be used to determine differences in gene expression profiles between patients and controls. Subsequently these biomarkers will be used to determine a difference between the various subtypes of the disease, and between the different affective periods of the disease. These biomarkers will be obtained by a `Suppression Subtractive Hybridisation' (SSH) of post mortal hippocampal, frontal lobe tissue, whole blood and lymphoblast cells. The analyses of these subtracted libraries will result in a list of differential expressed genes between patients and controls. With this information answers will be sought for questions like: which genes participate in the disease pathways, what are the gene expression differences between patient and control, what are the gene expression differences between the various subtypes and different affective periods of the disorder, which connections can be made between gene expression and the different genes and what are the parallels between the expression in brain and in blood?

                                            Researcher(s)

                                            Research team(s)

                                            Tech Transfer Project (TTP): Multiplex. 01/09/2004 - 28/02/2005

                                            Abstract

                                            This 3 month project intends to evaluate the proprietary multiplex PCR software. For this purpose 3 assays will be developed: 1) VTEC assay (verotoxine producing E. coli) containing 23 amplicons for the identification of 9 VTEC serotypes; 5 virulence genes and 9 virulence gene subtypes, 2) GMO assay containing 7 amplicons to detect 5 GMO events in Maize, 3) Diagnostic sequencing: using multiplex PCR to reduce number of PCR reactions and sequencing reactions and hence reducing overall sequencing cost.

                                            Researcher(s)

                                            Research team(s)

                                              Identification of biomarkers for bipolar disorder based on subtractive suppression hybridisation and micro-array technology. 01/01/2004 - 31/12/2006

                                              Abstract

                                              The goal of this project is to obtain biomarkers in blood for Bipolar Disorder (BP). Such biomarkers facilitate an individualised pharmacological profile which can lead to a more efficient treatment of patients with BP. Blood biomarkers will be determined using Suppression Subtractive Hybridization which is a technique that identifies differentially expressed genes between patients and control individuals. The obtained set of genes will additionally be analysed using micro-arrays to elucidate the differences between patient and control, the different subtypes of the disease and finally different phases of the disease. In this project we aim to solve following questions: What are the differences in gene expression in blood between patients and control individuals? What are the differences in gene expression in blood between the different subtypes of the disease and between the different mood phases (mania - depression) of the disease? What is the connection between the expression profile and genetic background of the disease? Are these potentials biomarkers also potential pharmacological targets?

                                              Researcher(s)

                                              Research team(s)

                                                Identification an characterization of susceptibility genes for bipolar affective disorder. 01/01/2003 - 31/12/2006

                                                Abstract

                                                Our project builds on findings from four independent genome-wide linkage scans for bipolar affective disorder that have identified several chromosomal loci that may harbour genes for this disorder. The availability of large patient samples and the use of high-throughput genotyping methods will allow searching for linkage disequilibrium in the most promising regions and finally the identification of disease-associated genes.

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                                                Research team(s)

                                                Identification of genes for affective disorders. 01/01/2003 - 31/12/2004

                                                Abstract

                                                The goal of this project is to identify and characterize genes for bipolar disorder (BP). Starting from BP candidate regions, identified through genome wide scans in Belgian and Swedish families, we will determine genes involved in BP by positional cloning. Hereto, linkage desequilibrium mapping will be performed using single nucleotide polymorphisms (SNPs) in large case/control samples from Belgian and northern Swedish origin.

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                                                Research team(s)

                                                  Development of Environmental Diagnostics based on Toxicogenomics and Bio-informatics. 01/10/2002 - 30/09/2006

                                                  Abstract

                                                  In the present proposal, different emerging technologies will be applied and integrated to create innovative, sensitive and discriminating technologies for environmental toxicity assessments: DNA array technology and bio-informatics. The global objective of the present proposal is to develop an expert system linked to a bio-informatics platform that can distinguish the mode of action of chemicals based on the gene expression profile it induces within in vitro cell systems. This model will be developed in two steps: we will first start to evaluate the potential to classify the toxic effects of a group of highly (structurally) diverse environmental contaminants representing the major toxicological modes of action. Using the gene expression profiles, measured using micro-arrays, we will construct a bio-informatics classifier as an expert model. This model will then be assessed on its robustness (how does the system recognize known molecules?), its correctness (how are chemicals with the same mode of action classified?) and its discriminatory power (how good can theoretically distinct modes of actions be recognised?) Once the initial version of the model works we will, in a second tiered step, further refine the classifier by studying chemicals with a defined mode of action: endocrine disrupting chemicals. Testing these highly similar working chemicals displaying more structural similarity on the in vitro system will be the ultimate challenge to explore the full potential of this promising technology.

                                                  Researcher(s)

                                                  Research team(s)

                                                  Identification of biomarkers for bipolar disorder by means of suppressive subtraction hyhridisation. 01/10/2002 - 30/09/2004

                                                  Abstract

                                                  Bipolar disorder (BP) is a severe psychiatric condition characterised by periods of mania and depression. The infliction is devastating for patient and his surroundings, on average 10 to 20% of the patients untimely die by suicide. BP has a lifetime prevalence of 0,5 ' 1,5%. Family, twin and adoption studies have shown that BP has a significant genetic component. Several linkage and association studies identified candidate susceptibility genes and candidate loci but till now none of these yielded a true disease-causing gene. The real problem of this disorder lies within the treatment. The evaluation period for subscribed medicines for a depressive period is 4 to 6 weeks, after witch another treatment can be tested when the previous one has proven to be ineffective. In 20% of the cases no effective treatment can be found within 2 ' 3 years. Moreover the effectiveness of mood stabilizing treatment such as the treatment with lithium, carbamazepine or valproate can only be evaluated when proven ineffective, when a patient refalls into an affective disordered condition. The goals of the proposed research is to discover biomarkers for BP, which can be used to determine differences in gene expression profiles between patients and controls. Subsequently these biomarkers will be used to determine a difference between the various subtypes of the disease, and between the different affective periods of the disease. These biomarkers will be obtained by a `Suppression Subtractive Hybridisation' (SSH) of post mortal hippocampal, frontal lobe tissue, whole blood and lymphoblast cells. The analyses of these subtracted libraries will result in a list of differential expressed genes between patients and controls. With this information answers will be sought for questions like: which genes participate in the disease pathways, what are the gene expression differences between patient and control, what are the gene expression differences between the various subtypes and different affective periods of the disorder, which connections can be made between gene expression and the different genes and what are the parallels between the expression in brain and in blood?

                                                  Researcher(s)

                                                  Research team(s)

                                                  Identification of genes for affective disorders : a family based approach. 01/01/2002 - 31/12/2005

                                                  Abstract

                                                  The laboratory of Molecular Genetics, University of Anwerp (UIA), initiated its research into the genetics of affective disorders aiming at identifying genes for bipolar disorder (BP) and recurrent unipolar (UP) disorder in 1989, a time when it was not so evident that, taken the available methodology and the complexity ofthe disorders, genes could be fo.und. Over the years different approaches were folIowed in our laboratory that included 1) positional cloning in multiplex families, 2) association studies of functional candidate genes in case/control samples, 3) development of new technologies to identify genes associated with triplet repeat expansions, and 4) genetic analysis of temperament dimensions as predisposing factors for affective disorders (see CV ofprincipal investigator). Although progress was made over the years it is important to recognise that no major breakthroughs were realised: as for to date neither us nor anyone else in the field of psychiatric genetics has identified a major gene for affective disorders or any other psychiatric disorder such as for example schizophrenia. It is therefore important that lessons are leamed from mistakes made in the past and that new opportunities offered by the large collections ofwell defined patient materials gathered over the years, and of new methodologies and technologies available today, are optimally exploited in order to guarantee results in the near future.

                                                  Researcher(s)

                                                  Research team(s)

                                                  Allowance for research equipment : BIOMEK FX liquid handling system. 01/01/2002 - 31/12/2002

                                                  Abstract

                                                  The BIOMEK FX is designed for high throughput processing of samples for molecular biological techniques such as : PCR reaction assembly; sequencing set-up and purification, plasmid isolation; set-up of genotyping reactions; streptavidin/biotine based separation techniques; reformatting of 96 and 384 wells plates.

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                                                    01/01/2001 - 31/12/2002

                                                    Abstract

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                                                      VIB-Cloning and identification of a gene on chromosome 18q22 or elsewhere in the genome. 01/01/1998 - 31/12/2001

                                                      Abstract

                                                      The goal of this project is to clone and characterize a gene for mood disorders. From the candidate region on chromosome 18q22 a YAC contig was constructed. This YAC contig will be used to isolate region specific triplet repeats and new candidate genes using the exontrapping technique. New triplet repeats are analyzed for expansions and known and new candidate genes are analyzed for mutations using direct cDNA sequencing. Once the gene has been cloned we will unravel the genomic structure of this gene. This implicates the determination of the intron-exon boundaries and the analysis and characterization of the promoter region.

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                                                      Research team(s)