Genomics and Personalised Medicine Notes

Introduction to Genomics and Personalised Medicine

  • Overview of PY5041 course by Dr. Ghazal.

What is Genomics?

  • Definition: The study of an organism's complete set of genetic information (genome).
  • Components: Includes both coding (genes) and non-coding DNA.
  • Human Genome: Approximately 3 billion base pairs, found in almost every cell, organized into 46 chromosomes.
  • Genetic Variability: Although nearly all humans share 99.9% of DNA sequence, mutations can lead to diseases like cancer.

Genomic Medicine

  • Definition: Branch of medicine that utilizes genomic information to tailor healthcare.
  • Impact on Healthcare: Genomic medicine is changing how diseases are diagnosed and treated, providing personalized treatment.
  • Pharmacogenomics: Subfield focused on how genes affect an individual's response to drugs, aiming to optimize drug efficacy and minimize adverse effects.

Genomic Testing in the NHS

  • Genetic testing commissioned and its role in drug prescription and treatment personalization.
  • Examples include predicting drug metabolism and potential side effects.

Key Areas of Genomics in Practice

  1. Gene Therapies: Novel therapeutics using gene modification.
  2. Targeted Treatments: Focusing therapy on specific mutations in diseases.
  3. Predicting Drug Responses: Using genomic data to guide treatment decisions.
  4. Repurposing Existing Drugs: Finding new uses for drugs based on genetic understanding.
  5. Identifying Adverse Reactions: Screening to prevent negative responses to medications.

Applications of Genomics in Healthcare

  • Disease Identification: Genetic factors in common diseases and syndromes such as diabetes and cancer.
  • Prenatal Testing: Early diagnosis of genetic conditions during pregnancy.
  • Infectious Disease Management: Genome sequencing aids in tracing outbreaks and effective treatments.
  • Gene Therapy: Corrective measures for genetic abnormalities and improving gene expressions.

Case Study: Familial Hypercholesterolaemia (FH)

  • Definition: Genetic condition causing high cholesterol from birth, increasing heart disease risk.
  • Genetic Basis: Caused by variants in LDLR, APOB, PCSK9, or APOE genes.
  • Family Screening: Essential for managing and identifying risk in relatives.

Cystic Fibrosis

  • Cause: Recessive mutation in CFTR gene leading to thick mucus production affecting lungs and digestion.
  • Treatment Advances: Move towards precision medicine targeting specific genetic defects.

Pharmacogenomics in Drug Therapy

  • CYP2D6 Gene: Critical for drug metabolism.
    • 25% of drugs are metabolized by CYP2D6, which varies among individuals.
    • Enzyme variants affect responsiveness to drugs like codeine.
  • Codeine: Metabolized into active morphine; efficacy varies based on CYP2D6 variants (e.g., poor metabolizers vs. ultra-rapid metabolizers).

Pharmacogenomics and Adverse Drug Reactions (ADRs)

  • Abacavir: Associated severe hypersensitivity reactions with genetic screening for HLA-B*57:01 allele to avoid toxicity.
  • Carbamazepine: Risks of severe skin reactions in genetically susceptible individuals; includes recommendations for screening HLA-B*15:02.

Benefits of Genomics in Medicine

  • Early Diagnosis & Treatment: Identification of diseases at an early stage improves outcomes.
  • Precision in Treatment: Tailored therapies based on genetic profiles reduce side reactions and enhance efficacy.
  • Research & Prevention: Understanding genetic risk factors can lead to better managing inherited conditions.

Ethical Considerations

  • Consent & Confidentiality: Emphasizes the need for informed consent before using genomic data, with a focus on protecting patient confidentiality.
  • GMC Guidelines: Balancing patient confidentiality against risks to family members due to genetic information.

Genetic Counseling

  • Definition: Process of helping patients understand their genetic results and implications for health.
  • Shared Decision Making: Important for enabling informed patient choices regarding their genomic data and related healthcare decisions.

Conclusion

  • The integration of genomics into health strategies signifies a shift towards more personalized and effective medical care.
  • Ethical considerations and the necessity of informed consent play a pivotal role in genomic applications.