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Clinical Genetics

  • A. M. W. van den Ouweland
  • R. van Minkelen
  • J. Knijnenburg
  • M. van Slegtenhorst
  • L. H. Hoefsloot
Chapter

Abstract

Clinical Genetics is the field studying the inheritance and causes of genetic disorders . A genetic disorder is defined as a pathological condition caused by an absent or defective gene or by a chromosomal aberration. Knowing the cause of a genetic disorder can be of crucial importance, not only for the patient, but also for his or her family. This chapter describes the use of several molecular methods, using examples from daily practice in the clinical genetic laboratory. The use of SNPs (single nucleotide polymorphisms) to detect large deletions and duplications is discussed. One paragraph describes how single gene sequencing is used to detect small mutations (nucleotide changes, small deletions and/or insertions) in the BRCA1 and BRCA2 genes that are tested routinely in the laboratory and take up more than 20% of the tests performed. The diagnosis of patients with a repeat expansion as their causative mutation asks for a different approach. Finally, the diagnostics for patients with intellectual disability is described. In the past years these patients often had no diagnosis, but with the introduction of exome sequencing in clinical practice, up to 30% of these patients now have a definitive diagnosis.

Keywords

Molecular diagnostics for inherited disease Clinical genetic laboratory Diagnostic microarrays Clinical whole exome sequencing 

Further reading

  1. Carter NP. Methods and strategies for analyzing copy number variation using DNA microarrays. Nat Genet. 2007;39(7 Suppl):S16–21.CrossRefPubMedPubMedCentralGoogle Scholar
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  3. Palma M, et al. BRCA1 and BRCA2: the genetic testing and the current management options for mutation carriers. Crit Rev Oncol Hematol. 2006;57(1):1–23.CrossRefPubMedGoogle Scholar
  4. Spurdle AB, et al. BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk. J Med Genet. 2012;49(8):525–32.CrossRefPubMedGoogle Scholar
  5. Stranneheim H, Wedell A. Exome and genome sequencing: a revolution for the discovery and diagnosis of monogenic disorders. J Intern Med. 2016;279(1):3–15.CrossRefPubMedGoogle Scholar
  6. Turnpenny PD, Ellard S. Emery’s essential elements of genetics, 14th edn. London: Elsevier Churchill Livingstone; 2011.Google Scholar
  7. Verkerk AJ, et al. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell. 1991;65(5):905–14.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2017

Authors and Affiliations

  • A. M. W. van den Ouweland
    • 1
  • R. van Minkelen
    • 1
  • J. Knijnenburg
    • 1
  • M. van Slegtenhorst
    • 1
  • L. H. Hoefsloot
    • 1
  1. 1.Clinical GeneticsErasmus MCRotterdamThe Netherlands

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