The human genome contains ~3 billion base pairs, approximately 1-5% of which are translated into functional proteins. Mutations in these proteins are the most likely to result in a direct phenotypic consequence. Although whole-genome sequencing (WGS) provides rich information about single nucleotide, structural, or copy number variants, whole-exome sequencing (WES) often makes more sense when time or resources are limited. For scientists looking at specific mutations or genes associated with particular diseases, custom-designed targeted panels offer even greater precision.
Whole-genome sequencing determines the order of all nucleotides in an individual’s DNA and can uncover variation in any part of the human genome, including coding, noncoding, and mitochondrial DNA (mtDNA) regions. In some instances, WGS is the better option because DNA variations outside protein-coding regions can affect gene activity and
protein production, potentially leading to genetic disorders. However, WGS requires more sequencing reagents and produces very large datasets that require sophisticated bioinformatics expertise to decipher, increasing both the cost and time required for analysis.
Whole-exome sequencing focuses on the genomic proteincoding regions (exons). Although WES requires additional reagents (probes) and some additional steps (hybridization), it is a cost-effective, widely used NGS method that requires fewer sequencing reagents and takes less time to perform bioinformatic analysis compared to WGS. Although the human exome represents only 1-5% of the genome, it contains approximately 85% of known disease-related variants.1 As such, researchers performing WES achieve comprehensive coverage of coding variants such as single nucleotide variants (SNVs) and insertions/deletions (indels). Despite lengthier sample preparation due to the additional target enrichment step, scientists benefit from quicker sequencing and data analysis compared to WGS. WES provides greater sequencing depth for researchers interested in identifying genetic variants for numerous applications, including population genetics, genetic disease research, and cancer studies.
Scientists sometimes require sequences from specific portions of the human genome, particularly when they are interested in a particular disease or collection of diseases. Custom panels provide this precision without driving up sequencing costs to achieve the required depth of target regions. For example, researchers may use a panel targeted to genes associated with hereditary eye disease as a first-tier test for patients with inherited retinal dystrophy,2 or for mapping pathogenic variants in breast cancer research.3 Custom panels are often very small (250 kb-5 Mb) thus bring down sequencing requirements drastically; answering distinct scientific questions becomes a lot easier. Although they are not suitable for broad discovery research, custom panels maximize sequencing economy for specific, suitable applications, especially when researchers use optimized panels for a particular disease or disorder.