Explain differences between whole-genome sequencing (WGS) and whole-exome sequencing (WES), and describe advantages and disadvantages of each approach for identifying disease-causing mutations in a genome. Which approach was used for the Human Genome Project?

Key Concepts

Whole-Genome Sequencing (WGS)

Whole-genome sequencing (WGS) involves determining the complete DNA sequence of an organism's genome, including all coding and non-coding regions. This comprehensive approach allows for the identification of all genetic variations, including single nucleotide polymorphisms (SNPs), insertions, deletions, and structural variants. WGS is particularly useful for discovering mutations that may not be present in coding regions, providing a broader understanding of genetic influences on diseases.

Whole-Exome Sequencing (WES)

Whole-exome sequencing (WES) focuses specifically on sequencing the exons, which are the protein-coding regions of the genome. Although exons make up only about 1-2% of the genome, they contain the majority of known disease-related mutations. WES is often more cost-effective and faster than WGS, making it a popular choice for identifying mutations associated with genetic disorders, but it may miss important regulatory or non-coding mutations.

Human Genome Project

The Human Genome Project (HGP) was an international research initiative aimed at mapping and understanding all the genes of the human species. It utilized whole-genome sequencing techniques to produce a complete reference sequence of the human genome. The HGP's findings have significantly advanced our understanding of genetics, paving the way for further research into genetic diseases and personalized medicine, and it primarily employed WGS to achieve its goals.