Liver disease and Next generation sequencing: a solution to the diagnostic problem?

genetics liver metabolic diseases

dr. K.E. Niezen-Koning
dr. T.J. de Koning

Nature of the research:
The student will actively participate in the development of a Next Generation Sequencing liver gene panel to be introduced in clinical practice

Fields of study:
pediatrics gastroenterology genetics

Background / introduction
During the last years the knowledge and management of liver disease are making much progress. However, still approximately 29 million persons in the European Union suffer from a chronic liver condition1. In Groningen a prospective study 2 showed that almost 23% of the patients who visited the departments of Internal Medicine and Gastroenterology from January to March 2010 were diagnosed with hepatobiliary diseases. A total of 1929 patients were included. For Pediatrics no such data are available on this subject.
Recent advances in genome sequencing technologies make it affordable to use next-generation sequencing (NGS) as a tool for the discovery of the genetic causes of liver disease. Therefore in Groningen the Depts. Genetics and Pediatrics/Laboratory of Metabolic Diseases have started several projects on targeted NGS. One of those projects includes the development of a Next Generation Sequencing liver gene panel. The NGS liver panel will be based on the clinical presentation of a patient with liver problems and allows the simultaneous analysis of more than 100 different liver genes in one run. Therefore, genes causing hepatomegaly, cholestasis and liver failure will be included in the liver panel. After thorough composition of the liver gene panel, in which the student participates actively, this diagnostic tool has to be tested and validated before it can be used in clinic.
In this innovative project the student will work with state-of-the art genetic techniques and its applications in clinical diagnostics (both children and adult patients).
Research question / problem definition
What is the diagnostic value of a NGS liver disorder gene panel?
The student will participate in the running activities of selecting the appropriate candidate genes for the panel on the basis of published data on genetic liver disorders. Subsequently the panel needs to be designed and tested. In parallel, workflows for selecting and including the right categories of patients (both adult and children) needs to be designed.
1. Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F. The burden of liver disease in Europe: a review of available epidemiological data. J Hepatol. 2013 Mar; 58(3):593-608. doi: 10.1016/j.jhep.2012.12.005.
2. Schreuder, R.M. Incidentie van lever- en galwegziekten: een prospectief onderzoek in de tweede lijn. 2010. Link:
3. Harrison RJ. Understanding genetic variation and function- the applications of next generation sequencing. Semin Cell Dev Biol. 2012 Apr;23(2):230-6. doi: 10.1016/j.semcdb.2012.01.006. Epub 2012 Jan 20.
4. Biesecker LG, Burke W, Kohane I, Plon SE, Zimmern R. Next-generation sequencing in the clinic: are we ready? Nat Rev Genet. 2012 Nov;13(11):818-24. doi: 10.1038/nrg3357.
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Laatst gewijzigd: 23 februari 2012