Birgit Sikkema-Raddatz, PhD

MSc: Biology, Martin Luther University Halle (Germany)

PhD thesis: Quality assessment op prenatal cytogenetic diagnosis: Some guidelines for handling amniotic fluid and chorionic villus material. University of Groningen, 2005. Full text

See PubMed for her papers

Birgit Sikkema-Raddatz works in the department’s Development and Innovation section, which focuses on translating new knowledge and technology into clinical genetic practice. Together with her research-team Birgit develops methods to unravel variants detected by Next Generation Sequencing data. Her main goal is to increase the knowledge available to help interpret whether these variants are harmful or benign. As a clinical laboratory specialist, she uses novel and newly developed methods to improve genetic diagnoses in patients referred to the department.

Birgit was previously involved in prenatal cytogenetic diagnosis but has switched to molecular cytogenetics (FISH and array techniques). Her focus in this clinical work was on assessing the quality of the techniques used, and her expertise in this field led to her being asked to organize the 2011 European Society of Human Genetics satellite meeting on “Arrays in daily practice: promises and pitfalls”.

More recently, Birgit’s focus has switched to the latest Next Generation Sequencing techniques and their implementation into clinical diagnostics . Together with her team, she demonstrated that targeted re-sequencing can replace Sanger sequencing in diagnostics, enabling the use of next-generation sequencing gene-panels as standard care. She has also developed enhanced data-analysis tools for non-invasive prenatal testing. In 2014 she received a grant from ZomMw, the Netherlands Organisation for Health Research and Development, for the development of diagnostic assays to detect structural variation relevant to almost all types of leukaemia with target locus amplification (TLA). Further, she is a member of the large multidisciplinary working group of the department that implemented rapid genome diagnostics for critically ill new-borns and infants (Five Genes Per Minute diagnostics, 5GPM). 5GPM has resulted in a 30% increase in diagnosis for these critically ill patients for whom routine clinical work up was unsuccessful.

Keywords: targeted sequencing, next generation sequencing, genotyping (SNP/CGH array) FISH, tissue culture, prenatal diagnosis

Selected papers

• 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 Dec 5;6:38359. doi: 10.1038/srep38359.
• 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 May;37(5):457-64. doi: 10.1002/humu.22969.
• Whole-exome sequencing is a powerful approach for establishing the etiological diagnosis in patients with intellectual disability and microcephaly. Rump P, Jazayeri O, van Dijk-Bos KK, Johansson LF, van Essen AJ, Verheij JB, Veenstra-Knol HE, Redeker EJ, Mannens MM, Swertz MA, Alizadeh BZ, van Ravenswaaij-Arts CM, Sinke RJ, Sikkema-Raddatz B. BMC Med Genomics. 2016 Feb 4;9:7. doi: 10.1186/s12920-016-0167-8.
• Targeted next-generation sequencing panels for monogenetic disorders in clinical diagnostics: the opportunities and challenges. de Koning TJ, Jongbloed JD, Sikkema-Raddatz B, Sinke RJ. Expert Rev Mol Diagn. 2015 Jan;15(1):61-70. doi: 10.1586/14737159.2015.976555.
• Targeted sequencing by proximity ligation for comprehensive variant detection and local haplotyping. de Vree PJ, de Wit E, Yilmaz M, van de Heijning M, Klous P, Verstegen MJ, Wan Y, Teunissen H, Krijger PH, Geeven G, Eijk PP, Sie D, Ylstra B, Hulsman LO, van Dooren MF, van Zutven LJ, van den Ouweland A, Verbeek S, van Dijk KW, Cornelissen M, Das AT, Berkhout B, Sikkema-Raddatz B, van den Berg E, van der Vlies P, Weening D, den Dunnen JT, Matusiak M, Lamkanfi M, Ligtenberg MJ, ter Brugge P, Jonkers J, Foekens JA, Martens JW, van der Luijt R, van Amstel HK, van Min M, Splinter E, de Laat W. Nat Biotechnol. 2014 Oct;32(10):1019-25. doi: 10.1038/nbt.2959.
• Central 22q11.2 deletions. Rump P, de Leeuw N, van Essen AJ, Verschuuren-Bemelmans CC, Veenstra-Knol HE, Swinkels ME, Oostdijk W, Ruivenkamp C, Reardon W, de Munnik S, Ruiter M, Frumkin A, Lev D, Evers C, Sikkema-Raddatz B, Dijkhuizen T, van Ravenswaaij-Arts CM. Am J Med Genet A. 2014 Nov;164A(11):2707-23. doi: 10.1002/ajmg.a.36711.
• Temporal and developmental-stage variation in the occurrence of mitotic errors in tripronuclear human preimplantation embryos. Mantikou E, van Echten-Arends J, Sikkema-Raddatz B, van der Veen F, Repping S, Mastenbroek S. Biol Reprod. 2013 Aug 22;89(2):42. doi: 10.1095/biolreprod.113.107946.
• TBX4 mutations (small patella syndrome) are associated with childhood-onset pulmonary arterial hypertension Kerstjens-Frederikse WS, Bongers EM, Roofthooft MT, Leter EM, Douwes JM, Van Dijk A, Vonk-Noordegraaf A, Dijk-Bos KK, Hoefsloot LH, Hoendermis ES, Gille JJ, Sikkema-Raddatz B, Hofstra RM, Berger RM. J Med Genet. 2013 Aug;50(8):500-6. doi: 10.1136/jmedgenet-2012-101152.
• Targeted Next-Generation Sequencing can Replace Sanger Sequencing in Clinical Diagnostics. Sikkema-Raddatz B, Johansson LF, de Boer EN, Almomani R, Boven LG, van den Berg MP, van Spaendonck-Zwarts KY, van Tintelen JP, Sijmons RH, Jongbloed JD, Sinke RJ. Hum Mutat. 2013 Apr 8. doi: 10.1002/humu.22332.
• Successful Noninvasive Trisomy 18 Detection Using Single Molecule Sequencing. van den Oever JM, Balkassmi S, Johansson LF, Adama van Scheltema PN, Suijkerbuijk RF, Hoffer MJ, Sinke RJ, Egbert B, Sikkema-Raddatz B, Boon EM. Clin Chem . 2013 Jan 11.
• The introduction of arrays in prenatal diagnosis: a special challenge. Vetro A, Bouman K, Hastings R, McMullan DJ, Vermeesch JR, Miller K, Sikkema-Raddatz B, Ledbetter DH, Zuffardi O, van Ravenswaaij-Arts CM. Hum Mutat . 2012 Jun;33(6):923-9. doi: 10.1002/humu.22050. Epub 2012 Apr 16.
• Genome-wide arrays in routine diagnostics of hematological malignancies. Simons A, Sikkema-Raddatz B, de Leeuw N, Konrad NC, Hastings RJ, Schoumans J. Hum Mutat . 2012 Jun;33(6):941-8. doi: 10.1002/humu.22057. Epub 2012 Apr 9. Review.
• Arrays in postnatal and prenatal diagnosis: An exploration of the ethics of consent. Dondorp W, Sikkema-Raddatz B, de Die-Smulders C, de Wert G. Hum Mutat . 2012 Jun;33(6):916-22. doi: 10.1002/humu.22068. Epub 2012 Apr 4.
• Practical guidelines for interpreting copy number gains detected by high-resolution array in routine diagnostics. Hanemaaijer NM, Sikkema-Raddatz B, van der Vries G, Dijkhuizen T, Hordijk R, van Essen AJ, Veenstra-Knol HE, Kerstjens-Frederikse WS, Herkert JC, Gerkes EH, Leegte LK, Kok K, Sinke RJ, van Ravenswaaij-Arts CM. Eur J Hum Genet . 2012 Feb;20(2):161-5. doi: 10.1038/ejhg.2011.174. Epub 2011 Sep 21.