A Review of DNA Enrichment Technologies - Next Generation Sequencing Technologies in Medical Genetics - page 28

further to completion using a smaller quantity of initial library (Gnirke et al. 2009 ).
In terms of performance, for smaller target sizes (~3.5 Mb), the uniformity and
specifi city of sequences obtained from a solution capture experiment tend to be
slightly higher than those of microarray capture (Mamanova et al. 2010 ). In con-
trast, for whole-exome captures, the NimbleGen platform, which is the only one to
use high-density overlapping baits, covers fewer genomic regions than the other
platform but requires the least amount of sequencing to sensitively detect small vari-
ants (Clark et al. 2011 ). Agilent is able to detect a greater total number of variants
with additional sequencing. Importantly, it was shown that that exome sequencing
can detect additional small variants missed by WGS (Clark et al. 2011 ). Signifi cantly,
solution captures have been used for mutation detection in congenital muscular dys-
trophy and hearing loss (Shearer et al. 2010 ; Valencia et al. 2012 ).

3.4 Summary

Advances in enrichment technologies, alongside NGS platforms, are accelerating the
discovery of genetic disorders at a rapid pace and are beginning to make their way
into clinical practice. Focused panel and exome NGS data are now being generated
by clinical laboratories at major genome centers nationwide by employing enrich-
ment technologies. The choice of specifi c enrichment method depends on the sample
number, the target size, and performance. For example, RDT has been the method of
choice for small (<1 Mb) NGS panels, but hybridization methods are routinely used
for exome capture. Interpreting the data with the aim of identifying pathogenic muta-
tions, among thousands to millions of variants, is still challenging and the creation of
clinical databases containing NGS results from a large number of normal controls
will greatly aid in the process. In the near future, NGS data may help defi ne genetic
profi les of patients and will be a step towards personalized medical care.

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