Whole Genome Sequencing (WGS) entails the complete sequencing of an individual's entire genome, encompassing all the nucleotide base pairs that make up our DNA. Unlike targeted approaches such as whole exome sequencing, which focuses solely on protein-coding regions, WGS provides a holistic view of both coding and non-coding regions, offering deep insights into genetic variation and functions.
Advantages of WGS:
High accuracy in detecting single nucleotide variants and small insertions/deletions.
Better identification of copy number variants (CNVs) due to uniform genome coverage.
Ability to detect certain structural rearrangements like balanced translocations that may be missed by arrays.
Complete sequencing of an individual's genome enables future reanalysis for newly discovered causal genes.
Potential for detecting variants in both protein-coding and non-coding regions.
Non-coding variant interpretation may pose challenges.
WGS aids in identifying novel genetic disease causes in research applications.
Limitations of WGS:
Virtual panels are sometimes used in WGS for rare disease diagnosis, focusing only on genes relevant to the patient's features.
Clinical interpretation of numerous variants identified poses a significant challenge.
More variants of uncertain significance are generated compared to targeted testing.
Increased risk of incidental findings compared to targeted testing.
Technical challenges exist in analyzing regions with pseudogenes or repetitive elements.
CNV and structural variant detection may be less accurate compared to gold standard techniques.
Not all conditions related to variations in short tandem repeats (STRs) are detected; PCR-based methods are often used separately.
Methylation status of DNA is not detected; ChIP-seq is more suitable.
Detection of mosaicism may be limited due to restricted read depth.
WGS test results may take longer to return compared to other genomic tests.
-Written by Sohni Tagore
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