Richard Sinke, PhD

Study: MSc in Biology, Catholic University Nijmegen 1987
PhD thesis: “Molecular characterization of chromosomal aberrations in human germ cell tumors” Catholic University Nijmegen 1996
Inaugural lecture: "De volgende generatie: in de hoogste versnelling" University of Groningen 2011 (in Dutch)

Contact: r.j.sinke umcg.nl

University Medical Center Groningen (UMCG)
Antonius Deusinglaan 1, 9713 AV Groningen
P.O. Box 30.0001, 9700 RB Groningen, the Netherlands
Phone +31 50 361 7100; Fax +31 50 361 7231

Keywords: Genome sequencing, hereditary diseases and human genetics, cardiogenetics, neurogenetics, translational research

Current work

My contribution to patient care focuses on expanding the application of novel genome analyses methods, such as next generation sequencing, SNP profiling and RNA sequencing, in the clinic. Our ultimate goal is to make personalized genomics work, not only for patient diagnostics and treatment, but also for disease prevention. By intensifying our department’s collaborations with medical specialists in the UMCG and from regional hospitals, I aim to enable the broader use and acceptance of genetic information in general healthcare and to provide knowledge and decision support for clinicians who request it.

Accordingly, my research aims to gain further understanding of the genetic causes of disease, not only for Mendelian disorders but also, increasingly, for common, complex diseases. We aim to identify mutations in genes or transcription profiles that contribute to inherited diseases and to discover how they are involved in disease development. This work focuses on translating the results from next-generation sequencing technologies, including whole genome-, exome- and RNA sequencing, into clinically meaningful information for patients and their families. We want to determine how this knowledge can be used to improve current routine diagnostics and how we can maximize the possibilities offered by modern technology.

Our projects include studies on implementing analyses of whole genome sequencing and its cost-effectiveness and exploring the possibilities of using an integrated DNA and RNAseq strategy to identify disease-causing genes. We are also developing bioinformatics methods for variant interpretation to accelerate diagnostics and gene-identification studies, for example, in patients and families with cardiomyopathies, movement disorders, dyslipidemias or blistering disorders. Our findings will, in turn, guide follow-up functional studies to reveal the consequences of genetic mutations and variations for the development of a disease and/or in determining variation in the phenotype. Extending multi-omics analysis strategies will be instrumental for developing our department’s concept of personalized medicine.

Recent projects

• 2017 ZonMW (Effectivity programme): lntensive Genetics: NGS in the NICU setting - a study on cost-effectiveness and quality of life (€398K)
• 2017 ZonMw, Personalised Medicine : WGS-first approach 'One-test-fits-all' to diagnose rare genetic disorders (€412K)
  UMCG part of these two above projects is €187K in total
• 2015 Fonds Erfelijkheidsonderzoek: Systems Medicine: towards diagnostics at maximum speed, Co-applicant (€320K)

Past work

• 2017-2018: Appointed interim head of Department of Genetics Jan 1st 2017 through Feb 1st 2018
• 2008-2017: I was head of the Genome Diagnostics Section (~68 fte). Ongoing research projects are being conducted in close collaboration with clinicians, bio-informaticians and researchers from our department and with many clinicians from the university hospital. Funding is provided through grants from ZonMw, Fonds Erfelijkheidsonderzoek, UMCG and CVON

Selected research papers

For a full list of publications see Google scholar
Peer-reviewed publications: 118
Chapters in books: 3
H-index: 41

1. Epidermolysis bullosa simplex caused by distal truncation of BPAG1-e: an intermediate generalized phenotype with prurigo papules. Turcan I, Pasmooij AMG, Gostyński A, van den Akker PC, Lemmink HH, Diercks GFH, Pas HH, Sinke RJ, Jonkman MF. J Invest Dermatol. 2017 May 27. pii: S0022-202X(17)31560-9.

2. GAVIN: Gene-Aware Variant INterpretation for medical sequencing. Van der Velde KJ, de Boer EN, van Diemen CC, Sikkema-Raddatz B, Abbott KM, Knopperts A, Franke L, Sijmons RH, de Koning TJ, Wijmenga C, Sinke RJ, Swertz MA. Genome Biol. 2017;18(1):6.

3. NIPTRIC: an online tool for clinical interpretation of non-invasive prenatal testing (NIPT) results. Sikkema-Raddatz B, Johansson LF, de Boer EN, Boon EM, Suijkerbuijk RF, Bouman K, Bilardo CM, Swertz MA, Dijkstra M, van Langen IM, Sinke RJ, Te Meerman GJ. Sci Rep. 2016;6:38359.

4. Association of Epidermolysis Bullosa Simplex With Mottled Pigmentation and EXPH5 Mutations. Turcan I, Pasmooij AM, Van den Akker PC, Lemmink H, Sinke RJ, Jonkman MF. JAMA Dermatol. 2016;152(10):1137-1141.

5. Population-based preconception carrier screening: how potential users from the general population view a test for 50 serious diseases. Plantinga M, Birnie E, Abbott KM, Sinke RJ, Lucassen AM, Schuurmans J, Kaplan S, Verkerk MA, Ranchor AV, van Langen IM. Eur J Hum Genet 2016. doi: 10.1038/ejhg.2016.43.

6. In-frame Exon Skipping in KRT5 due to Novel Intronic Deletion Causes Epidermolysis Bullosa Simplex, Generalized Severe. Gostyńska KB, Bremer J, van Dijk-Bos KK, Sinke R, Pasmooij AM, Jonkman MF. Acta Derm Venereol 2016. doi: 10.2340/00015555-2451.

7. CoNVaDING: Single Exon Variation Detection in Targeted NGS Data. Johansson LF, van Dijk F, de Boer EN, van Dijk-Bos KK, Jongbloed JD, van der Hout AH, Westers H, Sinke RJ, Swertz MA, Sijmons RH, Sikkema-Raddatz B. Hum Mutat 2016;37:457-464.

8. Biallelic Truncating Mutations in ALPK3 Cause Severe Pediatric Cardiomyopathy. Almomani R, Verhagen JM, Herkert JC, Brosens E, van Spaendonck-Zwarts KY, Asimaki A, van der Zwaag PA, Frohn-Mulder IM, Bertoli-Avella AM, Boven LG, van Slegtenhorst MA, van der Smagt JJ, van IJcken WF, Timmer B, van Stuijvenberg M, Verdijk RM, Saffitz JE, du Plessis FA, Michels M, Hofstra RM, Sinke RJ, van Tintelen JP, Wessels MW, Jongbloed JD, van de Laar IM. J Am Coll Cardiol 2016;67:515-525.

9. Calling genotypes from public RNA-sequencing data enables identification of genetic variants that affect gene-expression levels. Deelen P, Zhernakova DV, Haan M de, Sijde M van der, Bonder MJ, Karjalainen J, Velde KJ van der, Abbott KM, Fu J, Wijmenga C, Sinke RJ, Swertz MA, Franke L. Genome Med 2015;7(1):30.

National committees

• 2008-present: Member Management team, Dept of Genetics, UMCG
• 2008-2017: Chair of Genome diagnostics section, UMCG
• 2003-2008: Member Management team, Dept Medical Genetics, UMCU
• 2013-present: Board of Dutch Association for Human Genetics (NVHG)
• 2012-present: Plenary board of Association of Clinical Genetics Laboratory specialists (VKGL)
• 2014-present: Steering group Whole Genome Sequencing, Hartwig Medical Foundation: a collaboration of UMCG, UMCU, VUmc/AMC, NKI