The major goal of our projects is to locate genetic factors associated with complex diseases and to explore their contribution to these multifactorial disorders. In the Complex Genetics Section we mainly focus on the following topics and disorders:
In our research we produce a huge amount of data, such as genome-wide genotypes and gene expression data. These amounts cannot be analyzed without proper bioinformatic tools. We require people who can master statistical methods and have a biological mindset to decipher diseases in a mathematical fashion.
Type 1 diabetes (T1D) is a complex disorder in which multiple genes interact with environmental factors leading to severe disease phenotype. T1D damages several organs including kidneys, liver, vessels, nerves and brain, and eyes. Chronic debilitation and blindness are among the most common severe complications caused by T1D.
Our research line is studying the genetic factors of T1D as an immune-system associated disease. We have integrated several disciplines, including clinical, immunological, genetics, biostatistics methods, and advanced laboratory techniques to investigate the complex genetic architecture of T1D. We perform candidate gene association studies, as well as extensive genome sequencing to locate the T1D-associated genetic markers. Our project can provide good material and resources to students who would like to perform experimental research and write a scientific paper. During the 6-9 months of an internship, students can learn not only how to perform a systematic literature review, but also how to perform various lab techniques, design an experiment, do statistical analysis on their results, how to write up their research, and how to present their data to an audience.
We welcome students who are willing to work hard in a modern lab and in a multidisciplinary environment to produce worthwhile results.
Interested?
Contact: Dr. Stephan Perseng,
s.perseng@umcutrecht.nlDr. Bobby Koeleman,
b.p.c.koeleman@umcutrecht.nlEpilepsy is a term for a wide variety of syndromes that are mainly characterized by recurrent seizures. There is ample evidence for a genetic contribution to epilepsy and several genes have been detected for epilepsies that show a single gene inheritance pattern. These genes can be identified relatively simply in large families by positional cloning.
It is expected that more 'single gene' epilepsies will be unravelled as new large families are identified. The current challenge lies in discovering genes responsible for epilepsy syndromes that show a complex inheritance pattern, involving multiple genes and environmental factors. We regularly have projects in this area of research, involving lab work and statistical analysis.
Interested?
Contact: Dr. Carolien de Kovel,
c.dekovel@umcutrecht.nlPopulation variation in disease-like variants
Genetic association studies regularly find support for the involvement of certain genetic variants or closely linked mutations in the etiology of various complex diseases. These variants often increase disease risk only mildly. Though, in general, European populations are genetically fairly similar, genetic and environmental/cultural variation can still be large enough to change the mutation's significance or ease of detection. We would like to investigate how much odds ratios vary geographically and what could be the underlying cause for such variation. Within this topic, various short-term or longer-term projects are possible, involving database searches, literature searches, simulations and other techniques.
The role of non-coding elements
Apart from the protein-coding elements of DNA, many other sequences can be important for cell functioning. Online sequence and expression data are a rich source for detecting informative patterns. Students interested in this topic may come and discuss the possibilities.
Interested?
Contact: Dr. Carolien de Kovel,
c.dekovel@umcutrecht.nlSchizophrenia is a common psychiatric disorder affecting approximately 1% of the population. The disease has a strong hereditary component, but it has been suggested that multiple genes are involved as well as non-genetic factors. The aim of our studies is to determine the genetic basis of schizophrenia and identify the genetic risk factors for this psychiatric trait.
A whole-genome genetic study is currently being performed by our group in a large sample of patients and controls. This will lead to the identification of specific regions in the genome associated with schizophrenia. However, further analysis is required to narrow down each candidate region in order to identify the disease-associated genes. This project involves genotyping, haplotype analysis, sequencing, and data mining methods, among other techniques.
Expression and microarray studies are being performed to study the molecular pathways underlying schizophrenia and related phenotypes. Expression profiles of patients and controls are compared in order to identify specific gene networks associated with disease. This study may also involve the use of other species, such as mouse models, allowing us to access brain tissues that are known to be important in disease pathophysiology.
Vesico-Ureteral Reflux (VUR) is a congenital anomaly of the urinary tract that occurs in 1% of newborns. Children with this anomaly have an increased chance of ascending urinary tract infections and kidney damage. 10% to 30% of patients' siblings are also affected. We are therefore preparing both a linkage and an association study of children who have been operated upon in university hospitals. We hope to gain insight into the epidemiology and aetiology of this complex phenotype and to improve diagnostic procedures.
As a spin-off study, we want to use sequencing to investigate the role of a candidate gene for renal a-/dysplasia in a select group of patients from the genetics clinic.
Interested?
Contact: Dr. Jacques Giltay, MD,
j.c.giltay@umcutrecht.nl Autoimmune diseases are complex disorders in which multiple genes interact with environmental factors leading to severe phenotypes such as type 1 diabetes, rheumatoid arthritis, lupus, nephritis, Crohn’s disease, ulcerative colitis, coeliac disease, autoimmune hepatitis, systemic sclerosis, and multiple sclerosis. These disorders affect about 5% of the population and lead to damage in joints, blood vessels, nerves and organs, including the pancreas, intestine, kidneys, liver, brain, and eyes. Chronic life-long debilitation is the most common severe complication caused by autoimmune diseases, which may also lead to early mortality. Our group’s main research line is to apply genetic epidemiological tools along with state–of-the-art technologies to study the genetic factors of autoimmune disorders. We have integrated several disciplines (clinical, immunological, and genetic) with biostatistical methods to investigate the complex genetic architecture of autoimmune diseases. We perform candidate gene- and genome-wide association studies as well as extensive genome sequencing.
Our projects can offer good resources to students who would like to perform experimental research and participate in writing a scientific paper. During the internship, students can learn not only how to perform a systematic literature review, but also how to perform various lab techniques, design an experiment, and do statistical analyses on their own results. They can also learn how to write up their research and present their data to an audience. We welcome students who are willing to work hard in a modern genetics lab and in a multidisciplinary, stimulating environment to
produce worthwhile results.
Interested?
Contact: Dr. Bobby P.C. Koeleman:
b.p.c.koeleman@umcutrecht.nl