The Practice of Genetic in Clinical medicine.pptx

Clinical Genetics

1. The Practice of Genetics in Clinical Medicine Chapter 457 – Harrison’s Principles of Internal Medicine, 2 th Ed. Presented by: Youssef El Kheir Institution: Georgian National University | SEU

2. Scope of Clinical Genetics Increasing use of genetics for disease risk & prognosis Combines germline and somatic data

3. Evolution in Medical Genetics From Mendelian inheritance to genome wide analysis Now includes polygenic risk an d next generation sequences NGS

4. Germline vs Somatic Genetics Germline: inherited, affects all cells Somatic: acquired, often cancer-specific

5. Types of Germline Alterations Chromosomal anomalies (e.g., trisomy) Single-gene (Mendelian) mutations Polygenic risk via single nucleotide Polymorphisms SNPs

6. Genetic Testing Modalities Karyotype, Fluorescence In Situ Hybridization ( FISH ) , Polymerase Chain Reaction ( PCR ) , array comparative genomic hybridization (aCGH) , Next Generation Sequencing (NGS) Compare resolution, cost, diagnostic use

7. Next-Generation Sequencing (NGS) Comprehensive DNA sequencing Steps: library prep → sequencing → analysis

8. Indications for Genetic Testing Family history, syndromic features Unexplained early-onset disease Clinical indication → Test → Result

9. Penetrance & Expressivity Penetrance: % showing phenotype Expressivity: severity variation among carriers Important in disease interpretation

10. Germline Mosaicism Mutation in subset of parent's germline cells Child affected; parent asymptomatic Important in recurrence risk counseling

11. Pharmacogenomics in Practice Genotype-guided drug therapy Examples: warfarin, 6-MP, clopidogrel Improves safety and efficacy

12. Ethical, Legal & Social Issues (ELSI) Consent, privacy, genetic discrimination Impact on family members Counseling essential before testing

13. Genetic Counseling Workflow Pre-test counseling → Testing → Post-test review Ensures informed decisions

14. Incidental & Secondary Findings Unrelated but actionable mutations E.g., BRCA, Lynch syndrome Disclosure based on guidelines

15. Limitations and Risks False positives/negatives Variants of unknown significance (VUS) Psychological and social impact

16. Case Study 1: Familial Cancer Early-onset breast cancer in family Test: BRCA1/2

17. Case Study 2: Pharmacogenomics Warfarin dosing via CYP2C9/VKORC1 Clinical benefit: reduced bleeding risk

18. Integrating Genetics into Practice Use of EMR, clinical pathways Team approach with genetic counselors Ongoing physician education

19. Conclusion Genetics is integral to modern clinical care Genetics in Practice = Testing + Interpretation + Counseling + Application