Introduction

Whole-exome sequencing (WES) has witnessed a growing application in clinical diagnostics across various medical indications to elucidate the underlying genetic etiology of diseases. While single-gene testing and targeted gene panels remain common, particularly in cases where a specific disorder linked to a limited set of genes is suspected, the utilization of WES is progressively extending to earlier stages of diagnostic assessment. This trend is particularly notable in disorders characterized by genetic heterogeneity, such as complex neurologic conditions and multiple congenital anomalies.

WES serves as a valuable tool in gene discovery, particularly evident in extensive patient cohorts exhibiting conditions like autism, epilepsy, brain malformations, congenital heart disease, and neurodevelopmental disabilities. The application of WES has proven effective in identifying numerous novel disease genes and elucidating underlying pathways (Retterer, 2016).

Whole genome sequencing (WGS) and whole exome sequencing (WES) stand as prominent methodologies in contemporary genetic research. While both approaches afford a comprehensive perspective on an individual’s genetic constitution, critical distinctions exist between them, necessitating careful consideration by researchers in selecting the appropriate method. WGS encompasses the sequencing of the entire genome, encompassing both protein-coding and non-coding regions, thereby enabling the identification of nearly all genetic alterations in a patient’s DNA. In contrast, WES exclusively focuses on protein-coding regions. Each method possesses distinct strengths and limitations, finding diverse applications in genomics research.

WES specifically targets all protein-coding regions, constituting approximately 1% of the entire genome, yet responsible for 85% of known disease-causing variants. This precision facilitates molecular diagnoses of genetic disorders and facilitates the exploration of novel mutations and emerging pathogenic mechanisms. In comparison to whole genome sequencing, WES boasts advantages in terms of greater sequencing depth, yielding more efficient data (Schwarze, 2018).

Applications

WES serves as a valuable tool in advancing cancer research by facilitating the identification of variants or mutations contributing to tumor progression. The method provides comprehensive coverage of coding regions and a depth of coverage suitable for discerning both common and rare variants.

In scenarios where the research focus centers on pinpointing disease-causing variants within protein-coding regions, WES emerges as a particularly pertinent methodology. Its cost-effectiveness, compared to WGS, is attributed to its targeting of less than 2% of the genome. This economic advantage proves beneficial when investigating known genes or gene sets, or diseases associated with coding regions, allowing for an increased sample size. Additionally, in large-scale population comparisons, the relatively smaller data output of WES compared to WGS is advantageous, as the latter generates data on an order of magnitude larger, potentially posing challenges in data interpretation (Retterer, 2016).

Benefits

WES presents a notable advantage as a cost-effective approach for sequencing a substantial number of samples. Focusing solely on the exome, WES generates considerably less data compared to WGS, resulting in reduced sequencing and analysis costs. Furthermore, given that the exome encompasses a significant proportion of known disease-causing variants, WES emerges as a potent tool for elucidating the genetic origins of diseases (Schwarze, 2018).

Additionally, the comprehensiveness and impartiality of WES in analyzing all recognized disease-causing genes confer an additional advantage. This capability allows for the identification of more than one genetic condition, even in instances where the clinical presentation does not overtly suggest multiple diagnoses (Retterer, 2016).

Sample Requirements

We accept whole blood, buccal swab, saliva, and extracted DNA (from whole blood, Buccal swabs, or saliva) for germline WES.

Sample Specifications

  • Starting Materials: DNA, Whole Blood, Saliva, and Buccal Swab
  • Sequencing Platform: Illumina NovaSeq 6000 Platform
  • Exome Capture: Agilent SureSelect Exome Capture/IDT xGen Exome Capture
  • Sequencing Coverage:50X or 100X
  • Turnaround Time:2 Weeks (10 Working Days)
  • Quality Assurance: Performed by Licensed Personnel in Certified Laboratory
  • Deliverables: FASTQ, BAM, VCF Files, and Interpretation (optional)
  • Data Transfer: FTP, AWS and Data Uploading Services

Project Workflow

Bioinformatic Platform

Data Quality Control

Alignment

Variant Calling

Whole Exome Sequencing

DNA Extraction

Library Prep

Sequencing

Interpretation

Variant evaluation & Assertation

Test report & sign off