Table 2.

Advantages and challenges of various high-throughput methods.

	Targeted Gene Panel Sequencing	Whole-Genome/Exome Sequencing	CGH Microarray
Advantages	Higher coverage and sequencing depth	Massive parallel sequencing capability Identification of co-occurrence of mutations in different genes (all genes analyzed in parallel) Potential to identify new modifier genes/mutations Possibility to sequence non-coding variants and detect large insertion/deletion Quantitative and sensitive detection of genomic aberrations Constantly improving technology in gene capture and analysis	Identification of co-occurrence of CNVs in different genes Potential to identify new modifier genes/CNVs Quantitative and sensitive detection of genomic aberrations Relatively low costs Easy sample preparation Well-defined protocols and analysis pipeline Whole-genome analysis High resolution (up to 40 kb)
	Most suitable for clinical application
	Higher number of samples in a single run
	High degree of customizability
	Reduced computational and storage resources
	Low costs and turnaround time
	Comprehensive sequencing of disease-associated regions (disease-specific scopus)
	Single input of DNA/RNA
	Identification of co-occurrence of mutations in different genes
	Improved diagnostic rate (atypical phenotypes)
	Decreased sequencing costs per gene
	Constantly improving technology in gene capture and analysis
Challenges	Selection of genes relevant for the disease Need for improved DNA variant database Genomic analysis restricted to selected regions (new genes cannot be identified) Requires thorough validation of assay performance as per guidelines Potential inclusion of non-validated genes in genetic testing (new variants of unknown significance in clinic) Selection of suitable target capture approach and sequencing platforms	Large amount of data Relatively complicated workflow and analysis Low number of samples Requires thorough validation of assay performance as per guidelines Computational costs and resources; consumable costs Informatic challenges for analysis and clinical reporting Long-term storage and retrieval of data Revalidation of upgrades (methodology rapidly changing) Coverage and data quality can vary across genes Limited applications in routine diagnostics	Low sensitivity and high background Annotations of probes CNVs of unknown significance in clinic Analysis of only pre-defined sequences Dynamic range limited by scanner Hybridization potentially non-specific