The Genome and Whole Genome Sequencing


  • The genome is the collective total of an individual’s DNA, including all genes
    •  The human genome is composed of over 3 billion base pairs
    • Genes that code for proteins or other functional molecules only constitute a fraction of total DNA
    • Research is ongoing to look at all regions of the genome and their complex interactions
  • The Human Genome Project (completed 2003) established an overall ‘human’ consensus genome, though every individual has variations from the consensus in their personal genome
    • Most of an individual’s gene variations have no impact on gene function
    • Some variations that will impact gene function have an important role in disease causation
    • It can be unclear in some instances what the impact of certain genetic variations is, and whether or not they contribute to clinical findings
      • These are referred to as variants of uncertain significance (VUS)

Whole Genome Sequencing (WGS)

  • Analysis of the genome is typically performed using DNA sequencing technologies and often referred to as Whole Genome Sequencing (WGS)
  • WGS is generally considered in individuals with rare diseases or syndromes for whom testing of specific potentially disease-causing genes have not identified any disease causing gene mutations
  • WGS will not detect all types of genetic changes, such as large deletions of genes/DNA regions, and possibly smaller DNA insertions and deletions


  • WGS analysis will generally require a blood sample
    • Requirements will vary by laboratory
  • Results from WGS will not always yield definitive, actionable results that confirm a diagnosis
    • Findings may indicate a Variant of Uncertain Significance (VUS) and further follow up may be required over time to determine whether or not the variant is benign or pathogenic
    • WGS testing may often be most informative when an individual’s family members are also tested or willing to be tested to clarify result interpretation
  • Genetic counseling is recommended pre- and post-WGS analysis
  • Thorough informed consent process is imperative given the potential for results that may or may not be definitive

Learn More – Primary Sources:

National Human Genome Research Institute Fact Sheets

ACMG: Points to Consider for Informed Consent for Genome/Exome Sequencing

Locate a Genetic Counselor or Genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC