genetic testing

• Genetic Testing & Risk Prediction


  • Implications for oral health practitioners
• Human Genome Project

  International scientific research project determining the sequence of chemical base pairs which make up DNA and identifying and mapping the approximately 20,000-25,000 genes of the human genome
• Genetic diseases


  Caused by sequence variations in DNA
• Sequence variations in DNA

  • Disease-causing variants (mutations)
  • Susceptibility-creating, protective or disease-modifying variants
  • Polymorphisms (underlie individual differences)
  • Harmless variants
• Genetic variant


  Can cause or increase the risk of disease in a range of ways
• Types of genetic disease

  • Germline (Mendelian, Polygenic)
  • Somatic (non-heritable)
  • Multifactorial
• Oral environment

  • Host genome & complex oral ecology/genetics
  • Genotype x Genotype interactions (Co-evolution)
• Key issues

  • The HGP has seen an unprecedented rate of scientific discovery and pressures to apply emergent genetic information to clinical care
  • Efforts to incorporate genetic information into the clinical setting has often outpaced existing regulatory and educational environments
• Applications of genetics in dentistry

  • Genetic engineering
  • Gene therapy (CRISPR-Cas9)
  • Genetic testing & counselling (Diagnostic tests, Genetic screening & risk prediction, Pharmacogenetic testing)
• Genetic engineering

  • Growing new teeth in vitro/in vivo
  • Stem cell therapy for periodontitis
  • Changing the oral ecology
• Gene therapy

  • Congenital defects (CLP; agenesis; AI; DI)
  • Saliva
  • CRISPR/Cas9
• Genetic testing

  • Provide DNA sequence information
  • Classification based on methodology, gene tested, or purpose
• Types of genetic testing

  • Somatic cell genetic testing
  • Diagnostic testing for heritable mutations
  • Predictive testing for heritable mutations
  • Carrier testing for heritable mutations
  • Pharmacogenetic testing
• Ethical, legal, social implications

  • How should information from HGP be interpreted and used?
  • Who should have access to it?
  • How can people be protected from harm from improper disclosure or use?
  • Difficult to know when to use a test, how to interpret results, how to gain informed consent
  • Genetic information may have implications for other family members - confidentiality issues
  • Potential for discrimination - insurance, employment
  • Pleiotropy and comorbidity
  • How and when to communicate risk?
• The communication of uncertainty is perhaps the most difficult ethical and professional challenge faced by practitioners: 'Getting et al 2003'
• Limitations of genetic tests

  • Current methods do not detect all mutations
  • May not produce a clinically useful result if a variant of unknown clinical significance is identified
  • Provide probabilistic, not deterministic, information
  • There may be multiple genes that can cause the disease
  • A mutation in one gene can cause different diseases
  • Subject to laboratory error
• Other considerations


  • Direct to consumer testing
  • Lifestyle choices
  • Relationship testing
  • Insurance
  • Personalised dentistry c.f. population oral health
  • Simple messages for complex diseases
• Current and emerging technologies

  • Microarrays
  • Copy number variation
  • Q-PCR
  • Point-of-care testing (PCR-free)
  • Epigenetics
  • Proteomics
  • Whole-genome sequencing
• Skills practitioners will need

  • Take a family history, recognize patterns of inheritance, and carry out basic genetic risk calculations
  • Perform a head and neck examination with special attention to signs of major genetic disorders
  • Consider genetic conditions as a contributor in a differential diagnosis and modify treatment to accommodate genetic conditions
  • Recognize when to refer a patient for genetic screening, testing, and counselling
  • Interpret results of genetic tests and explain them to patients and family members
  • Explain and obtain informed consent for genetic testing
  • Access and critically assess appropriate literature
  • Include a genetics/development component in differential diagnosis
  • Work collaboratively with other members of the genetics health care team