The document outlines a genetics course led by Dr. Ahmed Elshebiny, focusing on medical genetics, basic principles, inherited disorders, and clinical applications. Key topics include gene therapy, chromosomal abnormalities, population genetics, and the genetic basis of diseases, extensively detailing inheritance patterns and genetic testing methods. The course aims to enhance understanding of how genetics influences both current and future medical practices.

2. Genetics Course: Mastering Medical Genetics Dr. Ahmed Elshebiny , MD Lecturer of Internal Medicine Faculty of Medicine, Menoufyia University Former Clinical Research Fellow, Joslin Diabetes Center, Harvard University

3. Course includes Basic Principles of Medical Genetics Genetic basis of disease: How diseases could be inherited? Medical Genetics in Clinical Practice : What is the impact of genetics on the present and future of Medicine? Let us start with this introductory video about genes

4. Medical Genetics Any application of genetic principles to medical practice. “ Genetics – study of individual genes and their effects”

5. Outline The Genetics course Basics Diseases Applications Structure & Facts Functions Inherited disorders Gene Therapy Cloning Stem Cell Genetic Testing

6. The Human Genome DNA structure and packaging Mitochondrial DNA Chromosomal Morphology Chromosome Replication Gene Expression Meiosis , Mitosis and Gametogenesis Epigenetics Population Genetics Consanguinity Family medical History Inherited disorders Mendelian inheritance Non Mendelian inheritance Cytogenetic abnormalities Basic Principles of Medical Genetics Structure & Facts of the Human Genome Functions & Physiology Clinical Genetics

7. 2- Genetic basis of disease Chromosomal abnormalities Genetics of Metabolism Genetics of Hemoglobinopathies Genetics of Bleeding disorders Genetics of Development Cancer Genetics

8. 3-Medical Genetics in Clinical Practice Genetic testing Genetic screening Molecular diagnostics Genetic engineering Gene Therapy Stem cell therapy Cloning

9. Genetics Course (1): Mastering Medical Genetics Basic Principles of Medical Genetics

10. The Human Nuclear Genome Genome = all of the DNA in an organism or cell Size of human genome: 3.4 billion base pairs Number of human genes: ~30,000 Genes vary in length and can cover thousands of bases average size: ~3,000 bp Only about 2% of the human genome contains coding genes Action of much of the genome is unknown

11. DNA Structure

12. DNA Structure

13. Epigenetics Epigenetics is the study of heritable changes in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence, hence the name epi- (Greek: επί - over, above) -genetics . These changes may remain through cell divisions for the remainder of the cell's life and may also last for multiple generations.

14. Chromosome Facts # of chromosomes per somatic cell: 22 pairs + 1 pair sex-determining chromosomes = 46 # of chromosomes per gamete (egg/sperm): 23 One chromosome of each pair donated from each parent’s egg or sperm Sex chromosomes: XY for males; XX for females Largest chromosome #1 = ~263 million base pairs (bp) Smallest chromosome Y = ~59 million bp

15. Chromosomal morphology methods Chromosomal staning FISH

16. Chromosomal Banding

17. Chromosomes

18. Mitochondrial DNA Circular Several copies No histones

19. Function of DNA The Human genome functions

20. Gene Expression Transcription Translation

21. Meiosis , Mitosis and Gametogenesis Mitosis is the process by which a cell separates its duplicated genome into two identical halves Meiosis is the process that transforms one diploid into four haploid cells. Where do your genes come from?

22. Genomic imprinting Most genes expressed equally from both alleles Small number of genes show differential expression dependent on parent of origin (mainly on chromosomes 6,7,11,14,15) ‘ Imprint’ is mediated by methylation  transcriptional inactivation Imprint persists through cell divisions in embryo Imprint removed at gametogenesis and then re-established according to sex of transmitting parent

23. Population Genetics Is the study of distributions of genes in populations Disease frequency Genotype frequencies from generation to generation Genetic Polymorphisms SNPs

24. Polymorphism Occurrence of 2 or more alleles at aspecific genetic locus in frequencies greater than can be explained by mutations alone Single nucleotide polymorphisms Restriction fragment length polymorphism (RFLP) Variable number tandem repeat polymorphism (VNTR)

25. Clinical genetics Clinical genetics is the practice of clinical medicine with particular attention to hereditary disorders.

26. Inherited disorders Cytogenetic Single gene Polygenic Multifactorial

27. Clinical Genetics Genotype: An individual’s genetic makeup - forms of a particular gene at a given locus Phenotype: The observable expression of a genotype Homozygous: Identical forms of a particular gene Heterozygous: Different forms of a gene– CARRIER if one normal and one abnormal Dominant: Condition phenotypically expressed in someone carrying one copy of a mutant gene Recessive: Condition phenotypic ally expressed only in someone with two copies of the mutant gene

28. Autosomal dominance Vertical transmission On average, 50% of offspring of affected parent will be affected Unaffected individuals do not transmit trait Males and females equally affected

29. Autosomal Dominant Conditions Marfan Syndrome Achondroplasia Familial (early-onset) Alzheimer Disease Huntington Disease Familial Hypercholesterolemia Familial Breast Cancer (BRCA1 or BRCA2 mutations)

30. Autosomal Recessive Inheritance Horizontal transmission; disease in siblings but usually not in earlier generations (unaffected, carrier parents) On average, 25% recurrence risk Males and females equally affected Increased consanguinity (relatedness) seen

31. Autosomal Recessive Conditions Sickle cell disease Cystic fibrosis Tay-Sachs disease Hemochromatosis Phenylketonuria Thalassemias

32. X-linked recessive inheritance Incidence of trait is much higher in males than females No father-to-son transmission 100% of daughters of affected males are (unaffected) carriers 50% of sons of carrier females are affected and 50% of daughters are carriers Trait may be transmitted through series of carrier females

33. X-linked recessive conditions Haemophilia Duchenne and Becker muscular dystrophy Androgen insensitivity syndrome Hunter syndrome Glucose-6-phosphate-dehydrogenase deficiency Bruton agammaglobulinaemia

34. Xplinked dominant Males and females affected, females usually less severely affected than males 1 in 2 risk to children of affected female (M+F) All daughters of affected male affected but no male to male transmission

35. X-linked dominant inheritance Males and females affected Vitamin D resistant rickets OTCD Fragile X syndrome Lethal in males Incontinentia pigmenti Rett syndrome XL chondrodysplasia punctata Goltz syndrome

36. Mitochondrial inheritance Mitochondria are exclusively maternally inherited Males and females affected but only females will transmit to offspring Risks to offspring of affected or carrier females are difficult to determine 0-100%

37. Family Medical History family medical history represents a “genomic tool” that can capture the interactions of genetic susceptibility, shared environment and common behaviors in relation to disease risk.

38. References Merck manual : online textbook E-medicine , online textbook , specialties,. BRS series : Genetics 2010 Lecture notes : Genetics (2006) Kumar & Klark : Clinical Medicine 2009 Other Web Resources & books

39. THANK YOU

40. Genetics Course (2): Mastering Medical Genetics Genetic Basis of Disease