Genetics and Internal Medicine  (1)
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Genetics and Internal Medicine (1)

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First Lecture in Genetics Course ( Internal Medicine) for undergraduates ( 5th year) /Menoufyia faculty of Medicine, Egypt/ April 2011

First Lecture in Genetics Course ( Internal Medicine) for undergraduates ( 5th year) /Menoufyia faculty of Medicine, Egypt/ April 2011

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Genetics and Internal Medicine  (1) Genetics and Internal Medicine (1) Presentation Transcript

  •  
  • 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
  • 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
  • Medical Genetics
    • Any application of genetic principles
    • to medical practice.
    • “ Genetics – study of individual genes and their effects”
  • Outline The Genetics course Basics Diseases Applications Structure & Facts Functions Inherited disorders Gene Therapy Cloning Stem Cell Genetic Testing
    • 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
  • 2- Genetic basis of disease
    • Chromosomal abnormalities
    • Genetics of Metabolism
    • Genetics of Hemoglobinopathies
    • Genetics of Bleeding disorders
    • Genetics of Development
    • Cancer Genetics
  • 3-Medical Genetics in Clinical Practice
    • Genetic testing
    • Genetic screening
    • Molecular diagnostics
    • Genetic engineering
    • Gene Therapy
    • Stem cell therapy
    • Cloning
  • Genetics Course (1): Mastering Medical Genetics Basic Principles of Medical Genetics
  • 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
  • DNA Structure
  • DNA Structure
  • 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.
  • 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
  • Chromosomal morphology methods
    • Chromosomal staning
    • FISH
  • Chromosomal Banding
  • Chromosomes
  • Mitochondrial DNA
    • Circular
    • Several copies
    • No histones
  • Function of DNA The Human genome functions
  • Gene Expression
    • Transcription
    • Translation
  • 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?
  • 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
  • Population Genetics
    • Is the study of distributions of genes in populations
    • Disease frequency
    • Genotype frequencies from generation to generation
    • Genetic Polymorphisms
    SNPs
  • 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)
  • Clinical genetics
    • Clinical genetics is the practice of clinical medicine with particular attention to hereditary disorders.
  • Inherited disorders
    • Cytogenetic
    • Single gene
    • Polygenic
    • Multifactorial
  • 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
  • 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
  • Autosomal Dominant Conditions
    • Marfan Syndrome
    • Achondroplasia
    • Familial (early-onset) Alzheimer Disease
    • Huntington Disease
    • Familial Hypercholesterolemia
    • Familial Breast Cancer (BRCA1 or BRCA2 mutations)
  • 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
  • Autosomal Recessive Conditions
    • Sickle cell disease
    • Cystic fibrosis
    • Tay-Sachs disease
    • Hemochromatosis
    • Phenylketonuria
    • Thalassemias
  • 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
  • X-linked recessive conditions
    • Haemophilia
    • Duchenne and Becker muscular dystrophy
    • Androgen insensitivity syndrome
    • Hunter syndrome
    • Glucose-6-phosphate-dehydrogenase deficiency
    • Bruton agammaglobulinaemia
  • 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
  • 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
  • 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%
  • 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.
  • 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
  • THANK YOU
  • Genetics Course (2): Mastering Medical Genetics Genetic Basis of Disease