1. General Pathology
    2. 1. The Cell as a Unit of Health and Disease
    2. Cellular Response to Stress and Toxic Insults
    3. Inflammation and Repair
    4. Hemodynamic Disorders, Thromboembolic Disease, and Shock
    5. Genetic Disorders
    6. Diseases of the Immune System
    7. Neoplasia
    8. Infectious Diseases
    9. Environmental and Nutritional Diseases
    10. Diseases of Infancy and Childhood
  2. Systemic Pathology: Diseases of Organ Systems
    3. 11. Blood vessels
    12. The Heart
    13. Diseases of White Blood Cells, Lymph Nodes, Spleen, and Thymus
    14. Red Blood Cell and Bleeding Disorders
    15. The Lung
    16. Head and Neck
    17. The Gastrointestinal Tract
    18. Liver and Gallbladder
    19. The Pancreas
    20. The Kidney
    21. The Lower Urinary Tract and Male Genital System
    22. The Female Genital Tract
    23. The Breast
    24. The Endocrine System
    25. The Skin
    26. Bones, Joints, and Soft Tissue Tumors
    27. Peripheral Nerves and Skeletal Muscles
    28. The Central Nervous System
    29. The Eye
General Pathology
5. Genetic Disorders
GENES AND HUMAN DISEASES
Mutations
MENDELIAN DISORDERS
Transmission Patterns of Single-Gene Disorders
▢ Autosomal Dominant Disorders:
▢ Autosomal Recessive Disorders:
▢ X-Linked Disorders:
Biochemical and Molecular Basis of Single-Gene (Mendelian) Disorders
▢ Enzyme Defects and Their Consequences:
▢ Defects in Receptors and Transport Systems:
▢ Alterations in Structure, Function, or Quantity of Nonenzyme Proteins:
▢ Genetically Determined Adverse Reactions to Drugs:
Disorders Associated with Defects in Structural Proteins
▢ Marfan Syndrome:
▢ Ehlers-Danlos Syndromes (EDS):
Disorders Associated with Defects in Receptor Proteins
▢ Familial Hypercholesterolemia:
Disorders Associated with Defects in Enzymes
▢ Lysosomal Storage Diseases:
▢ Glycogen Storage Diseases (Glycogenoses):
Disorders Associated with Defects in Proteins That Regulate Cell Growth
COMPLEX MULTIGENIC DISORDERS
CHROMOSOMAL DISORDERS
Normal Karyotype
Structural Abnormalities of Chromosomes
Cytogenetic Disorders Involving Autosomes
▢ Trisomy 21 (Down Syndrome):
❖ Clinical features:
◉ General appearance:
    Image 1
    Image 2
  1. Characteristic facial features
    1. Flat facial profile
    2. Oblique palpable fissures
    3. Epicanthic fold
  2. Widespread first leg toe
  3. Simian crease
  4. Abundant neck skin
◉ Severe mental retardation:
◉ Congenital defects:
  1. Congenital heart defects (Defects of endocardial cushion)
    1. Defects in ostium primum
    2. Atrial septal defects
    3. Atriventricular valve malformations
    4. Ventricular malformations
    5. Ventricular septal defects
  2. Atresia of Oesophagus and Small bowel
❖ High risk of:
  1. Acute leukemia
    1. Acute lymphoblastic leukemia
    2. Acute myeloid leukemias
      1. Acute megakaryoblastic leukemia
❖ At 40 years of age: Neuropathologic changes characteristic of Alzheimer disease
❖ Abnormal immune responses:
  1. Serious infections
  2. Lung infection
  3. Thyroid autoimmunit
▢ Other Trisomies:
▢ Chromosome 22q11.2 Deletion Syndrome:
Cytogenetic Disorders Involving Sex Chromosomes
▢ Klinefelter Syndrome:
▢ Turner Syndrome:
▢ Hermaphroditism and Pseudohermaphroditism:
SINGLE-GENE DISORDERS WITH NONCLASSIC INHERITANCE
Diseases Caused by Trinucleotide-Repeat Mutations
▢ Fragile X Syndrome and Fragile X Tremor/Ataxia:
Mutations in Mitochondrial Genes—Leber Hereditary Optic Neuropathy
Genomic Imprinting
▢ Prader-Willi Syndrome and Angelman Syndrome:
Gonadal Mosaicism
MOLECULAR GENETIC DIAGNOSIS
Diagnostic Methods and Indications for Testing
▢ Laboratory Considerations:
▢ Indications for Analysis of Inherited Genetic Alterations:
▢ Indications for Analysis of Acquired Genetic Alterations:
PCR and Detection of DNA Sequence Alterations
Molecular Analysis of Genomic Alterations
▢ Fluorescence in Situ Hybridization (FISH):
▢ Multiplex Ligation-Dependent Probe Amplification (MLPA):
▢ Southern Blotting:
▢ Cytogenetic Array Technology:
Polymorphic Markers and Molecular Diagnosis
▢ Polymorphisms and Genome-Wide Analyses:
Epigenetic Alterations
RNA Analysis
Next-Generation Sequencing
▢ Bioinformatics:
▢ Clinical Applications of NGS DNA Sequencing:
▢ Future Applications: