Whole-exome sequencing (WES) is helping physicians diagnose a genetic condition that has defied diagnosis by traditional means. The implication here is that exons in the nuclear genome are sequenced in the hopes that, by comparison with the genomes of nonaffected individuals, a diagnosis might be revealed.

What are the strengths and weaknesses of this approach?

Key Concepts

Whole-Exome Sequencing (WES)

Whole-exome sequencing (WES) is a genomic technique that focuses on sequencing all the protein-coding regions, or exons, of the genome. These exons represent about 1-2% of the entire genome but contain approximately 85% of known disease-related variants. WES is particularly useful for identifying genetic mutations associated with various conditions, making it a powerful tool in clinical diagnostics.

Comparative Genomics

Comparative genomics involves comparing the genomic data of affected individuals with that of nonaffected individuals to identify genetic variations that may contribute to disease. This approach helps in pinpointing mutations that are likely pathogenic, as it highlights differences that could be responsible for the observed condition. It is essential for interpreting WES results and understanding the genetic basis of diseases.

Strengths and Weaknesses of WES

The strengths of WES include its ability to uncover rare genetic variants and its efficiency in diagnosing complex genetic disorders that traditional methods may miss. However, its weaknesses involve the potential for incidental findings, the challenge of interpreting variants of uncertain significance, and the fact that WES does not capture non-coding regions or structural variants, which can also play critical roles in genetic diseases.