Biomedical Engineering Reference
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different genes (entries in OMIM). NGS has brought new ways of addressing mono-
genic disorders. Because of its large capacity to unbiasedly survey the exome and
genome, NGS is well suited in the usage of discovering the cause of rare genetic
disorders (Chap. 8 ). When properly executed, the WES approach may dramatically
reduce the required sample number needed for a successful outcome. The use of
NGS has frequently resulted in identifying disease genes with even a limited num-
ber of patient samples (Fig. 1.1 ; Kalay et al. 2011 ; Krawitz et al. 2010 ; Kuhlenbäumer
et al. 2011 ; Musunuru et al. 2010 ; Ng et al. 2010a , b ; Puente et al. 2011 ; Simpson
et al. 2011 ). Novel and causative variants have recently been discovered for diverse
types of diseases, including neuropathy cases (Brkanac et al. 2009 ), Clericuzio type
poikiloderma with neutropenia (Volpi et al. 2010 ), familial exudative vitreoretinop-
athy (Nikopoulos et al. 2010 ), immunological disorders (Bolze et al. 2010 ; Byun
et al. 2010 ), intellectual disabilities (Abou Jamra et al. 2011 ; Shoubridge et al.
2010 ), cancer predisposition (Shoubridge et al. 2010 ), and other abnormalities
(Barak et al. 2011 ; Bilgüvar et al. 2010 ; Otto et al. 2010 ). Novel genes for non-
syndromic (Rehman et al. 2010 ; Walsh et al. 2010 ) and syndromic (Pierce et al.
2010 ; Zheng et al. 2011 ) hearing loss were also identifi ed recently by the targeted
NGS approach. These studies show that the targeted genomic region (Rehman et al.
2010 ) or whole exome NGS (Pierce et al. 2010 ; Walsh et al. 2010 ), followed by
verifi cation from nonconsanguineous families, and by functional and immunolabel-
ing examinations, can reveal critical disease-causing genes from small pedigrees.
The success of NGS in research has already resulted in its translational uses in
clinical care, and many of them are for diagnostic mutation detection of focused
panels of disease genes which will be covered in Chaps. 6 and 7 . In clinical practice,
the Cincinnati Children's Medical Center's Molecular Genetics Laboratory ( http://
default/ ) offers NGS panels for fatty acid oxidation disorders, hearing loss, and
immunodefi ciencies, namely, bone marrow failure syndromes, chromosome break-
age disorders, dyskeratosis congenital, Fanconi anemia, and severe combined
immunodefi ciency. Other clinical laboratories offering clinical NGS panels include
Emory Genetics Laboratory, Baylor College of Medicine, GeneDx, and Prevention
Genetics. The clinical uses of NGS will only continue to grow as NGS panels
expand to WES analysis and eventually WGS analysis.
Many NGS technologies have been introduced in the past 8 years. Each platform
possesses its advantages and disadvantages such as throughput, accuracy, run times,
price, and ease of use. Due to this large array of NGS platform options, clinical
laboratories are adopting the technologies that meet their specifi c needs. For exam-
ple, the Illumina HiSeq 2500 has been the choice for large NGS panels with fast
turnaround times. In contrast, Illumina's MiSeq may provide enough coverage for
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