Whole Exome Sequencing (WES) Service

Demo Results

These example plots highlight typical WES outputs—coverage/QC performance, variant summary, enrichment overview, and genome-wide signal visualization—for quick project review.

Whole Exome Sequencing FAQs

1. What are the applications of whole exome sequencing?

Human genome contains approximately 180,000 coding regions (exome), constituting about 1.7% of a human genome. It is estimated that 85% of the disease-causing mutations occur in the exome. Therefore, whole exome sequencing is a potential contributor to the understanding of human diseases. Whole exome sequencing is a cost-effective and powerful tool, especially suitable for bigger sample size and high coverage. Whole exome sequencing is mainly used to investigate the genetic cause of both Mendelian and common diseases such as cancer and diabetes.

Figure 1. Application of whole exome sequencing in a complex disease.

2. What variations can whole exome sequencing detect?

Whole exome sequencing can detect SNPs, InDels, and maybe copy number variations (CNVs).

3. How do I determine the sequencing depth?

Sequencing depth is an important factor for high-throughput sequencing. One paper published in the journal Genomics & Informatics revealed that the sequencing depth of whole exome sequencing can affect the discovery rates of variations. To summarize, the number of deleterious SNPs and InDels detected in the coding regions was only weakly increased a depths more than 120×. In other words, a sequencing depth of 120× can be considered reasonable when using the exome capture sequencing technique to identify significant variations in diagnostic studies.

4. What are the disadvantages of whole exome sequencing?

Whole exome sequencing is characterized by lower cost, increased sequence coverage, as well as sensitive and specific identification. Nevertheless, Whole exome sequencing cannot detect structural variants, and has a limited view, i.e., only coding regions. Not all targets are captured (approximately 80%), and it is difficult to capture GC-rich regions.

5. What's the difference between WES and WGS?

Whole exome sequencing (WES) targets protein-coding regions for efficient variant discovery with manageable data volume, while WGS profiles the entire genome for maximum breadth and re-mining potential.

6. What regions does whole exome sequencing cover?

WES focuses on exome capture of protein-coding regions (target size typically in the tens of megabases, depending on the capture design), with coverage varying across GC-rich or hard-to-capture targets.

7. What QC metrics are reported for WES?

We report key coverage and capture QC such as on-target performance, duplication, and coverage distribution (including common coverage threshold summaries across targets) to help you assess data usability quickly.

8. What files will I receive from a WES project?

Typical deliverables include FASTQ (raw reads), BAM/CRAM (aligned reads), VCF (variant calls), plus an annotated variant table and a concise QC/report package (RUO).

9. Can WES results be used for cohort-level comparison?

Yes. For multi-sample studies, outputs can be generated in a consistent format and (optionally) with cohort-aware analysis to improve comparability across samples and reduce batch-related interpretation issues.

Reference:

1. Kyung Kim, et al. Effect of Next-Generation Exome Sequencing Depth for Discovery of Diagnostic Variants. Genomics & Informatics. 2015, Jun; 13(2): 31–39.

Whole Exome Sequencing Case Studies

First missense mutation outside of SERAC1 lipase domain affecting intracellular cholesterol trafficking

Journal: Nuerogenetics

Impact factor: 3.269

Published online: 7 October 2015

Abstract

MEGDEL syndrome is a rare inborn error of metabolism. This syndrome has been associated to mutations in the serine active site containing 1 (SERAC1) gene. The authors reported a new homozygous mutation in the SERAC1 gene via whole exome sequencing at CD Genomics. This is the first missense mutation outside of serine-lipase domain of the protein that affects the intracellular cholesterol trafficking.

Results

1. Mutations in the SERAC1 gene

To date, 19 mutations in the SERAC1 gene have been identified in patients with MEGDEL syndrome (Table 1). Only three are missense mutations which are localized within the lipase domain. The p.D224G is the first missense mutation outside of lipase domain.

2. Missense mutation (p. D224G)

Using whole exome sequencing, the authors identified a novel pathogenic homozygous mutation in the SERAC1 gene. This missense mutation changed a aspartic acid to glycine (Figure 1d). The pathogenic role of p.D224G is supported by in silico analysis, the conservation of the mutant amino acid residue (Figure 1d), and the accumulation of cholesterol (Figure 1e).

Figure 1. The position of D224 mutation in various species (d). Intracellular cholesterol trafficking in fibroblasts derived from healthy individual and the SERAC1 patients. U1866A is an inhibitor of cholesterol trafficking.

Reference:

1. Rodríguez-García M E, et al. First missense mutation outside of SERAC1 lipase domain affecting intracellular cholesterol trafficking. Neurogenetics, 2016, 17(1): 51-56.