Cognitive Genetics

Our research group Cognitive Genetics is part of the research cluster Medical Genetics of the Faculty of Pharmaceutical, Biomedical and Veterinary Sciencesof the University of Antwerp. The research cluster, in combination with diagnostic and clinical units forms the Center of Medical Genetics. We are part of the University of Antwerp research excellence center GENOmics in MEDicine (GENOMED), that was recently awarded a prestigious Methusalem grant. Our group is also a founding member of the expertise technology consortium Precision Medicine Technologies (PreMeT) for logistic support of our industrial collaborations.

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Cognitive Genetics

Mission

Our mission is to identify genetic causes of cognitive disorders and to study the molecular defects in order to eventually develop rational therapy.

Embedding

Our research group Cognitive Genetics is part of unit Medical Genetics of the Faculty of Pharmaceutical, Biomedical and Veterinary Sciences of the University of Antwerp. In combination with diagnostic administrative and clinical units the research unit forms the Center of Medical Genetics. We are part of the University of Antwerp research excellence center GENOmics in MEDicine (GENOMED), that was recently awarded a prestigious Methusalem grant. Our group is also a founding member of the expertise technology consortium Precision Medicine Technologies (PreMeT) for logistic support of our industrial collaborations.

What we do

Our research has focussed on intellectual disability and syndromic forms of autism. Both disorders are frequent. For example, intellectual disability is estimated to affect 2-3% of the total population, while autism rates appear to be increasing, with reported prevalence as high as 1 in 44. Both disorders have a strong genetic component, that remains unveiled in the majority of cases. As the causes of the cognitive disorders are genetically extremely heterogeneous, the identification of the cause of the disorder requires an approach specific for this type of disorder.

We identify novel causes of cognitive disorders starting from rare, affected patients or families and from patients with specific chromosomal abnormalities, including microdeletions, translocations and fragile sites. To achieve this, we are constantly incorporating and optimizing the latest technologies relevant for our search and are also developing novel technologies. For the functional study of the genes of interest, we rely on animal and cellular disease models.

For example, our functional research on the knockout mouse model of Fragile X syndrome—a common cause of cognitive impairment and autism—led to human drug trials, offering hope for targeted treatments. To further enhance our understanding of the disease's molecular basis, we replicate disease-related mutations in human embryonic stem cells. These cells are then differentiated into various types of brain cells, known as neurons, allowing us to study the disorders in disease-relevant tissue.

Intellectual Disability research (Post Doc Dale Annear)
Fragile X syndrome research (PhD student Mathijs van der Lei)
Helsmoortel-Van der Aa Syndrome research (PhD student Claudio D’Incal)
neurodevelopmental disorder research (PhD student Kirsten Van Rossem)
neurodevelopmental disorder research (PhD student Jolien Huyghebaert)
ADHD research (PhD student Luna Deconinck)

Dynamic mutations in intellectual Disability and Autism.
Neurodevelopmental disorders (NDDs), like intellectual disability (ID) and autism-spectrum disorder (ASD), are a group of conditions that affect people's cognitive abilities and development. Recent research has shown that a specific type of repetitive DNA sequence called CGG trinucleotide repeat may play a role in these disorders. Fragile X Syndrome (FXS), a common form of intellectual disability and autism, is one example of a disorder associated with this repeat. The number of disorders associated with these repetitive sequences has been increasing, particularly in the field of neurology. Many of these disorders affect the brain and nervous system, leading to problems with thinking, movement, and development. However, it is challenging to study and identify these disorders because the repetitive regions of DNA are difficult to work with in the lab, and they are often overlooked in standard genetic tests. Our research aimed to understand the characteristics of CGG repeats throughout the human genome and their connection to neurodevelopmental disorders such as ID and ASD. Within this research we applied advancements in whole-genome sequencing (WGS) technologies and bioinformatic analysis methods to study the CGG repeats in the human genome. By doing this, we hoped to shed light on their role in these disorders and uncover new insights into where CGG repeats may be contributing to as-of-yet-identified NDDs.
PhD student: Dale Annear
Promotor: Frank Kooy
A combination of the Multi-Electrode Array (MEA) and Live Mouse Tracker (LMT) as versatile drug screening platform for fragile X syndrome
Fragile X syndrome is the most common inherited cause of intellectual disability and autism, with a prevalence of approximately 1 in 4000–7000 males and 1 in 6000–11000 females. Current treatment is symptomatic and no specific treatment options are available for the disorder yet. However, combination therapies of novel or repurposed available drugs may lead to more effective treatment of core symptoms of fragile X syndrome, but such an approach faces the challenge of having to test multiple compounds and a combination of a series of drugs, likely in various concentrations each. This would be much too time-consuming and costly for current approaches. Therefore, we have developed a versatile drug screening platform consisting of the multi electrode array (MEA) and live mouse tracker (LMT) to assess at first glance the effectiveness of novel (combination) therapies. The MEA system measures real time electrophysiological activity, with quantification of network parameters of complete neuronal networks in a time efficient and high throughput manner. The LMT is used for behavioral analysis, dissecting up to 35 distinct (social) behaviors of up to four mice from a single 24-hour recording. The goal of my research is to utilize our drug screening platform for the preclinical validation of novel compounds and/or repurposed drugs for fragile X syndrome.
PhD student: Mathijs van der Lei
Promotor: Frank Kooy
Molecular and functional study of two frequent syndromic Autism Spectrum Disorders: Helsmoortel-Van der Aa Syndrome and Fragile X Syndrome.
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PhD student: Claudio D’Incal
Promotors: Frank Kooy & Wim VandenBerghe
Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy.
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PhD student: Kirsten Van Rossem
Promotor: Frank Kooy
Dissection of the AnkyrinG interactome in a cellular model for neurodevelopmental disorders.
Neurodevelopmental disorders (NDDs) are the consequence of a disturbed development of the central nervous system (CNS). NDDs can be caused by genetic and environmental factors, or by a combination of both. The genetic causes of NDDs are very heterogeneous, but show convergence on specific pathways across distinct NDDs. The hypothesis whether aberrations in genes in the same pathway or protein-protein interaction network result in a similar cellular phenotype, and if the total mutational load on the network defines the phenotypic outcome, will be studied during this project. Since there is a scarcity in disease relevant tissue to study, we will set up a cellular model to study the functional effects of mutations in the AnkyrinG network. We will do so by introducing mutations in genes of this network in stem cells that will be differentiated into neuronal cells. These mutated cells will be functionally assessed. By using this cell model, more knowledge about the relation between distinct NDDs will be obtained.
PhD student: Jolien Huyghebaert
Promotor: Frank Kooy & Geert Vandeweyer
Epigenetic factors contributing to ADHD and resillence.
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PhD student: Luna Deconinck
Promotor: Frank Kooy