Biomedical Engineering Reference
In-Depth Information
Chapter 4
Application of Next-Generation-Sequencing
to the Diagnosis of Genetic Disorders:
A Brief Overview
Next-generation-sequencing (NGS) holds a number of advantages over traditional
Sanger sequencing, the most obvious being able to do panel testing in a shorter span
of time at a lower cost (Hu et al. 2009 ). A number of phenotypically similar diseases
can have a number of different genetic causes (Hoischen et al. 2010 ). This genetic
heterogeneity, seen in congenital muscular dystrophies (Chap. 6 ) , congenital disor-
ders of glycosylation (CDG), and hearing loss (Chap. 7 ) , can be addressed by NGS
by simply sequencing all genes related to specifi c phenotypes (Rehman et al. 2010 ;
Lim et al. 2011 ; Valencia et al. 2012 ). In the case of CDG, NGS is a time- and cost-
effective tool for comprehensive mutations screening of metabolic diseases caused
by mutations in different genes of a common pathway. In addition, its use can be
applied to disorders that have a variable presentation but can raise fl ags for a certain
set of diseases such as mitochondrial defects. One distinct advantage can be seen in
the fi eld of cancer genetics where panel testing can save a signifi cant amount of time
by reaching a diagnosis (Chan et al. 2012 ). An interesting application of NGS is in
the application of noninvasive prenatal diagnosis of aneuploidies and trisomies 21,
18, and 13 (Chap. 5 ; Chiu et al. 2008 ).
In this chapter, we discuss the recent application of NGS in the diagnosis of a
number of genetic disorders. We briefl y introduce each genetic disorder and men-
tion the corresponding gene panel that has been examined via NGS technologies to
address the issue of genetic heterogeneity. We begin by introducing CDG in the next
section to demonstrate how NGS can be used to screen for mutations in different
genes of a common metabolic pathway.
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