Next-generation sequencing (NGS)

In the past years, new methods of high-throughput sequencing have been developed which are referred to as next-generation-sequencing (NGS).

They are based on the idea that several million DNA fragments are sequenced in parallel in one sequencing run. Initially used by researchers primarily to identify new disease genes, NGS has since revolutionised the world of human genetics. It is now possible to include virtually all monogenic disease conditions in the diagnosis, especially those with distinct genetic heterogeneity.

We at Bioscientia have developed gene panels that allow sequencing several hundred disease genes simultaneously. When assembling the gene panels, we take all genes into consideration whose mutations are associated with the corresponding phenotype according to the latest literature. This approach allows us to simultaneously evaluate or clarify possible differential diagnoses. The corresponding gene sections (exons and adjacent intronic sequences) are sequenced using Illumina systems after these have been enriched from the overall genomic DNA (sequence capture using the NimbleGen technology from Roche). The NGS data are processed by a biodata pipeline that is continuously being further developed by our team of bioinformatics specialists. The achieved depth of sequencing moreover allows detecting structural variants such as deletions and duplications, so-called CNVs (copy number variations) which are not detected by conventional sequencing – a benefit in particular for such genes for which no MLPA kits are available. Pathogenic changes discovered through NGS are validated using conventional Sanger sequencing or MLPA, array CGH or qPCR (for CNVs). The finding returned to the physician who sent the sample includes a detailed interpretation of the identified variants by an experienced team of biomedical experts and human geneticists.

NGS analytics is increasingly replacing the conventional step-by-step approach to diagnose heterogeneous diseases (“genewise” analysis) using Sanger sequencing because it offers the following advantages:

  • NGS is much more cost-efficient, faster and of better quality (e.g. detecting deletions/duplications) than the conventional Sanger sequencing given the corresponding expertise
  • Some patients have mutations in more than one disease gene which went undetected in conventional gene-wise sequencing (more comprehensive analysis).
  • Misinterpretations can be avoided in comparison to the conventional single gene analysis using NGS.


Bioscientia NGS panels

The Bioscientia Center for Human Genetics currently offers the following diagnostic panels to analyse various disease conditions. We are continuously expanding our range of analytic services. We regularly adjust the composition of our gene panels to include the latest scientific findings.
The NGS screening method in our laboratory is certified by CAP (College of American Pathologists).

If you have any questions about this screening method or about our latest developments, please call us at: +49 61 32 7 81 4 33.

Detection rates achieved by NGS analytics of gene panels

Being one of the first laboratories to introduce NGS analytics, the Center for Human Genetics has several years of experience in analysing large diagnostic gene panels. The comprehensive NGS analytics allows the genetic cause of a patient’s disease to be determined quickly and with a high probability. Some indications have a very high detection rate, even up to 90% for some conditions (see literature). If no pathogenic changes in the analysed genes can be determined for a patient, further diagnostic measures may be recommended after consultation, e.g. exome sequencing.


Sample requirements

Sample requirements: Preferably send 3-5 ml fresh EDTA blood instead of DNA*

*In-house DNA extraction methods assure the comparable DNA quality required for this test

Request form: Molecular genetic diagnostics



Tobias Eisenberger, Christian Decker, Milan Hiersche, Ruben C. Hamann, Eva Decker, Steffen Neuber, Valeska Frank, Hanno J. Bolz, Henry Fehrenbach, Lars Pape, Burkhard Toenshoff, Christoph Mache, Kay Latta, Carsten Bergmann. An efficient and comprehensive strategy for genetic diagnostics of polycystic kidney disease. PLoS One. 2015 Feb 3;10(2):e0116680

Beck BB, Phillips JB, Bartram MP, Wegner J, Thoenes M, Pannes A, Sampson J, Heller R, Göbel H, Koerber F, Neugebauer A, Hedergott A, Nürnberg G, Nürnberg P, Thiele H, Altmüller, J, Toliat MR, Staubach S, Boycott KM, Valente EM, Janecke, AR, Eisenberger T, Bergmann C, Tebbe L, Wang Y, Wu Y, Fry AM, Westerfield M, Wolfrum U, Bolz HJ. Mutation of POC1B in a severe syndromic retinal ciliopathy. Hum. Mutat. 2014 Oct; 35(10):1153-62.

Khan AO, Bergmann C, Eisenberger T, Bolz HJ. A TULP1 founder mutation, p.Gln301*, underlies a recognisable congenital rod-cone dystrophy phenotype on the Arabian Peninsula. Br J Ophthalmol. 2014 Oct 23. pii: bjophthalmol-2014-305836.

Fehrenbach H, Decker C, Eisenberger T, Frank V, Hampel T, Walden U, Amann K, Krüger-Stollfuß I, Bolz HJ, Häffner K, Pohl M, Bergmann C. Mutations in WDR19 encoding the intraflagellar transport component IFT144 cause a broad spectrum of ciliopathies. Pediatr Nephrol. 2014 Aug;29(8):1451-6.

Huppke P, Wegener E, Böhrer-Rabel H, Bolz HJ, Zoll B, Gärtner J, Bergmann C. Tectonic gene mutations in patients with Joubert syndrome. Eur J Hum Genet 2014 Aug 13. doi: 10.1038/ejhg.2014.160.

Eisenberger T, Di Donato N, Baig SM, Neuhaus C, Beyer A, Decker E, Mürbe D, Decker C, Bergmann C, Bolz HJ. Targeted and genomewide NGS data disqualify mutations in MYO1A, the „DFNA48 gene“, as a cause of deafness. Hum. Mutat. 2014 May; 35(5):565-70.

Frank V, Habbig S, Bartram MP, Eisenberger T, Veenstra-Knol HE, Decker C, Boorsma RAC, Goebel H, Nürnberg G, Griessmann A, Franke M, Borgal L, Kholi P, Völker LA, Dötsch J, Nürnberg P, Benzing T, Bolz HJ, Johnson C, Gerkes EH, Schermer B, Bergmann C. Mutations in NEK8 link multiple organ dysplasia with altered Hippo signalling and increased c-MYC expression. Hum Mol Genet 22:2177-85, 2013.

Eisenberger T, Neuhaus C, Khan AO, Decker C, Preising MN, Friedburg C, Bieg A, Gliem M, Issa PC, Holz FG, Baig SM, Hellenbroich Y, Galvez A, Platzer K, Wollnik B, Laddach N, Ghaffari SR, Rafati M, Botzenhart E, Tinschert S, Boerger D, Bohring A, Schreml J, Koertge-Jung S, Schell-Apacik C, Bakur K, Al-Aama JY, Neuhann T, Herkenrath P, Nuernberg G, Nuernberg P, Davis JS, Gal A, Bergmann C, Lorenz B, Bolz HJ. Increasing the Yield in Targeted Next-Generation Sequencing by Implicating CNV Analysis, Non-Coding Exons and the Overall Variant Load: The Example of Retinal Dystrophies. PLoS ONE. 2013; 8(11): e78496.

Hoff S, Halbritter J, Epting D, Frank V, Nguyen TM, van Reeuwijk J, Boehlke C, Schell C, Yasunaga T, Helmstädter M, Mergen M, Filhol E, Boldt K, Horn N, Ueffing M, Otto EA, Eisenberger T, Elting MW, van Wijk JA, Bockenhauer D, Sebire NJ, Rittig S, Vyberg M, Ring T, Pohl M, Pape L, Neuhaus TJ, Elshakhs NA, Koon SJ, Harris PC, Grahammer F, Huber TB, Kuehn EW, Kramer-Zucker A, Bolz HJ, Roepman R, Saunier S, Walz G, Hildebrandt F, Bergmann C, Lienkamp SS. ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3. Nat Genet. 2013; 45(8):951-6.

Schmidts M, Frank V, Eisenberger T, Al Turki S, Bizet AA, Antony D, Rix S, Decker C, Bachmann N, Bald M, Vinke T, Toenshoff B, Di Donato N, Neuhann T, Hartley JL, Maher ER, Bogdanović R, Peco-Antić A, Mache C, Hurles ME, Joksić I, Guć-Šćekić M, Dobricic J, Brankovic-Magic M, Bolz HJ, Pazour GJ, Beales PL, Scambler PJ, Saunier S, Mitchison HM, Bergmann C. Combined NGS approaches identify mutations in the intraflagellar transport gene IFT140 in skeletal ciliopathies with early progressive kidney Disease. Hum Mutat. 2013; 34(5):714-24.

Metzker ML. Sequencing technologies – the next generation. Nat Rev Genet. 2010; 11(1):31-46.

Voelkerding KV, Dames SA, Durtschi JD. Next-Generation Sequencing: From Basic Research to Diagnostics. Clin Chem. 2009; 55(4):641-58.