Next-generation sequencing approach for the diagnosis of human diseases: open challenges and new opportunities

. 2018 Apr 30;29(1):4-14.

eCollection 2018 Apr.

Next-generation sequencing approach for the diagnosis of human diseases: open challenges and new opportunities

Chiara Di Resta^{1

2}, Silvia Galbiati², Paola Carrera^{2

3}, Maurizio Ferrari^{1

2

3}

Affiliations

¹ Vita-Salute San Raffaele University, Milan, Italy.
² Genomic Unit for the Diagnosis of Human Disorders, Division of Genetics and Cell Biology, IRCCS San Raffaele Hospital, Milan, Italy.
³ Laboratory of Clinical Molecular Biology and Cytogenetics, IRCCS San Raffaele Hospital, Milan, Italy.

PMID: 29765282
PMCID: PMC5949614

Next-generation sequencing approach for the diagnosis of human diseases: open challenges and new opportunities

Chiara Di Resta et al. EJIFCC. 2018.

. 2018 Apr 30;29(1):4-14.

eCollection 2018 Apr.

Authors

Chiara Di Resta^{1

2}, Silvia Galbiati², Paola Carrera^{2

3}, Maurizio Ferrari^{1

2

3}

Affiliations

¹ Vita-Salute San Raffaele University, Milan, Italy.
² Genomic Unit for the Diagnosis of Human Disorders, Division of Genetics and Cell Biology, IRCCS San Raffaele Hospital, Milan, Italy.
³ Laboratory of Clinical Molecular Biology and Cytogenetics, IRCCS San Raffaele Hospital, Milan, Italy.

PMID: 29765282
PMCID: PMC5949614

Abstract

The rapid evolution and widespread use of next generation sequencing (NGS) in clinical laboratories has allowed an incredible progress in the genetic diagnostics of several inherited disorders. However, the new technologies have brought new challenges. In this review we consider the important issue of NGS data analysis, as well as the interpretation of unknown genetic variants and the management of the incidental findings. Moreover, we focus the attention on the new professional figure of bioinformatics and the new role of medical geneticists in clinical management of patients. Furthermore, we consider some of the main clinical applications of NGS, taking into consideration that there will be a growing progress in this field in the forthcoming future.

Keywords: causative mutations; coverage; diagnostics; genetic medicine; genetics; incidental findings; inherited disorders; next generation sequencing; sequence depth; variants interpretation.

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Figures

**Figure 1**
Advantages and challenges of the use of gene panel NGS testing and WES So far the application of WES in clinical diagnostics presents more open challenges (B) than targeted sequencing (A).

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References

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[1] Koboldt DC, Steinberg KM, Larson DE, Wilson RK, Mardis ER. The next-generation sequencing revolution and its impact on genomics. Cell. 2013;155: 27–38. doi:10.1016/j.cell.2013.09.006 - PMC - PubMed

[2] Koboldt DC, Steinberg KM, Larson DE, Wilson RK, Mardis ER. The next-generation sequencing revolution and its impact on genomics. Cell. 2013;155: 27–38. doi:10.1016/j.cell.2013.09.006 - PMC - PubMed

[3] Grumbt B, Eck SH, Hinrichsen T, Hirv K. Diagnostic applications of next generation sequencing in immunogenetics and molecular oncology. Transfus Med hemotherapy Off Organ der Dtsch Gesellschaft fur Transfusions-medizin und Immunhamatologie. 2013;40: 196–206. doi:10.1159/000351267 - PMC - PubMed

[4] Grumbt B, Eck SH, Hinrichsen T, Hirv K. Diagnostic applications of next generation sequencing in immunogenetics and molecular oncology. Transfus Med hemotherapy Off Organ der Dtsch Gesellschaft fur Transfusions-medizin und Immunhamatologie. 2013;40: 196–206. doi:10.1159/000351267 - PMC - PubMed

[5] Vrijenhoek T, Kraaijeveld K, Elferink M, de Ligt J, Kranen-donk E, Santen G, et al. Next-generation sequencing-based genome diagnostics across clinical genetics centers: implementation choices and their effects. Eur J Hum Genet. Nature Publishing Group; 2015;23: 1142–1150. doi:10.1038/ejhg.2014.279 - PMC - PubMed

[6] Vrijenhoek T, Kraaijeveld K, Elferink M, de Ligt J, Kranen-donk E, Santen G, et al. Next-generation sequencing-based genome diagnostics across clinical genetics centers: implementation choices and their effects. Eur J Hum Genet. Nature Publishing Group; 2015;23: 1142–1150. doi:10.1038/ejhg.2014.279 - PMC - PubMed

[7] Coonrod EM, Durtschi JD, Margraf RL, Voelkerding K V. Developing genome and exome sequencing for candidate gene identification in inherited disorders: an integrated technical and bioinformatics approach. Arch Pathol Lab Med. 2013;137: 415–433. doi:10.5858/arpa.2012-0107-RA - PubMed

[8] Coonrod EM, Durtschi JD, Margraf RL, Voelkerding K V. Developing genome and exome sequencing for candidate gene identification in inherited disorders: an integrated technical and bioinformatics approach. Arch Pathol Lab Med. 2013;137: 415–433. doi:10.5858/arpa.2012-0107-RA - PubMed

[9] Peters DG, Yatsenko SA, Surti U, Rajkovic A. Recent advances of genomic testing in perinatal medicine. Semin Perinatol. 2015;39: 44–54. doi:10.1053/j.semperi.2014.10.009 - PMC - PubMed

[10] Peters DG, Yatsenko SA, Surti U, Rajkovic A. Recent advances of genomic testing in perinatal medicine. Semin Perinatol. 2015;39: 44–54. doi:10.1053/j.semperi.2014.10.009 - PMC - PubMed

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Next-generation sequencing approach for the diagnosis of human diseases: open challenges and new opportunities

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Next-generation sequencing approach for the diagnosis of human diseases: open challenges and new opportunities

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