Epidemiology and Genetic Screening Quiz

Introduction to the cell membrane and organelles

• This presentation introduces the basic structure of the human cell, the cell membrane, and cellular organelles.
• Learning objectives include describing the basic human cell structure, outlining cell membrane structure and function, outlining cellular organelle structure and function, and discussing dysfunction implications in various organelles.
• The presentation also introduces the use of light and electron microscopes in examining cells, showing the levels of magnification needed to observe different cellular components.
• A diagram illustrates the relative size of various cell components from the naked eye level to the atomic level.

Learning Objectives

• The objectives are to describe the basic human cellular structure, the components of the cell membrane, the components of cellular organelles and the implications of their dysfunction.

Microscopy

• Microscopes, both light and electron, are explained and their relative magnifications are illustrated for accurate observation of cells.

Eukaryotic Organelles

• A eukaryotic cell diagram shows the common organelles shared by all eukaryotic cells
• Common organelles include mitochondria, Golgi apparatus, endoplasmic reticulum with membrane-bound ribosomes, endosome, lysosome, cytosol, and peroxisome, free ribosomes, nucleus, and the plasma membrane.
• Their relative sizes (volumes) within a liver cell are tabulated, illustrating the cytosol as the major intracellular compartment in a liver hepatocyte(54% volume of cell).

Cell Membrane

• The cell membrane is described as a mosaic lipid bilayer with a lipid bilayer of 5 nm thickness.
  • Phosphoglycerides, sphingolipids, and sterols make up the major lipids.
  • The presentation outlines passive and active transport mechanisms across the cell membrane. (diffusion, facilitated diffusion, and active transport)

Protein Trafficking

• A "road map" diagram shows the process of protein traffic within a eukaryotic cell.
• This process, starting from the nucleus, includes transport to various organelles and to the cell exterior via vesicles.
• Different ways of vesicle budding and fusion during vesicular transport are discussed.
• Various signal sequences directing proteins to different intracellular locations are outlined.

Nucleus

• The nucleus is a membrane-bound organelle.
• The nucleus contains chromatin material (DNA).
• Nuclear pores control molecule import and export and are highlighted.
• The role of Ran GTPase in the directionality of transport through nuclear pores is explained through a reaction diagram.

Mitochondrion

• The structure of a mitochondrion, including its outer membrane, matrix space, cristae space, intermembrane space, and inner membrane are described.
  • The pathway of protein transport into mitochondria. Different complexes like TOM, TIM, and OXA are shown in a diagram.

Peroxisomes

• Role of peroxidase in various oxidation reactions.
• Detoxification processes involving peroxisomes.

Endoplasmic Reticulum (ER)

• The endoplasmic reticulum (ER) has smooth and rough regions.
  • Rough ER synthesizes proteins using attached ribosomes and manufactures membranes.
  • Smooth ER is a transitional area for transport vesicles carrying protein products.
  • It is involved in lipid synthesis and metabolic waste/drug detoxification.

The Golgi Apparatus

• The Golgi apparatus receives and modifies proteins and lipids from the ER.
• The modified molecules are then sent to various target locations (intracellular or extracellular).

Oligosaccharides

• Oligosaccharides act as tags to mark the state of protein folding within the Golgi.

The unfolded protein response (UPR)

• The unfolded protein response (UPR) is a cellular response to the accumulation of misfolded proteins in the ER.
  • The response activates additional processes to deal with the misfolded proteins (protein folding capacity of the ER, and protein degradation apparatus)

Physiology and pathology

• Roles of the ER stress response in multiple systems from bone marrow to brain to intestine are discussed
  • Relevant role in disease include but are not limited to diabetes, neurodegeneration, ischemia, cancer and other diseases

Protein Trafficking

• The mechanisms behind protein trafficking within the cell are explained including coated vesicles (clathrin, COPII, COPI), and their role.
  • Different proteins involved in vesicle formation and fusion like SNAREs are discussed.

Endocytosis

• Phagocytosis and pinocytosis are mechanisms for internalizing materials.
• Lysosomes are crucial for the endocytotic pathways.
• The endocytic pathway from the plasma membrane to lysosomes is explained (including pathways and relevant components).

Low-density Lipoprotein (LDL)

• LDL structure is described and the receptor-mediated endocytosis of LDL is outlined.

Storage of proteins in recycling endosomes

• Storage of proteins within recycling endosomes, and their use.
• For example, insulin-stimulated transporters can be stored for later use, when the signal is present.

Pathways synopsis

• Endocytosis leads to early endosomes, and then to either recycling endosomes (reusing components) or to late endosomes, which then lead to lysosomes (degrading materials).

The Degradation and Recycling of Macromolecules in Lysosomes

• A general overview of the mechanism that lysosomes use for degradation.

Lysosome acid hydrolases

• The role of lysosomes acid hydrolases enzymes (and their substrates, like proteases) in acidic conditions is detailed.

Autophagy

• The importance of autophagy for degrading damaged proteins and organelles is highlighted.

Lysosome storage diseases

• A description of the types of diseases and resulting effects on the human body.

Organization of the human genome

• Intragenic and extragenic DNA structures are compared.

DNA (Structure and function)

• The structure of DNA (double helix of complementary nucleotide chains) and its hereditary function are described.
  • Diagrammatic illustration of this structure.

Chromosomal DNA Packing

• Eukaryotic DNA organization into chromosomes along with the roles of nucleosomes, telomeres, and centromeres are described.
  • Processes like replication origins and the DNA packaging are explained.
• The role of proteins in the compaction and organization of chromatin is discussed.
• The structure and function of a nucleosome core particle and its role in chromatin compactness are outlined.

The human karyotype

• A description of the typical human chromosome composition.

The organization of genes on chromosomes.

• The types of genes (coding vs noncoding) and how they are spatially arranged are contrasted.

Gene organization.

• A description of the typical eukaryotic gene structure including introns, and coding regions.

mtDNA

• A description of mitochondrial DNA (mtDNA) structure and general properties.
• Contrast between nuclear DNA and mtDNA structure and properties is detailed.

DNA Methylation

• How DNA methylation can suppress gene expression
• How these methylation patterns can be inherited is explained

Genomic imprinting and X-chromosome inactivation

• These are epigenetic phenomena.

DNA replication

• The process of DNA replication is outlined.
  • Potential errors and their ramifications if not corrected, are examined.
  • Telomere structure and function, and their relation to aging are examined.

DNA replication

• Fundamental mechanisms of DNA replication and repair are covered, including the actions of enzymes and proteins.
  • The importance of base pairing, the asymmetrical replication fork, proofreading mechanisms, and the synthesis of short RNA primer molecules are detailed.
• Processes like sliding ring to DNA polymerase, the fundamental similarity between prokaryotes and eukaryotes, and mismatch repair are addressed in the slides.
• The semi-conservative nature of DNA replication is illustrated.

Telomeres and Telomerase

• Description of telomere structures and their importance for chromosome protection, as well as the enzyme (telomerase) used for replication of the telomeres are discussed.
• Telomere shortening and the relation to the Hayflick limit is addressed.

Biological ageing

• The overview examines theories of aging, including their genetic, biochemical, and biological nature.

Cancer

• Definition and fundamental process of carcinogenesis are examined.
• Factors related to carcinogenesis and cancer types are explored.
  • Hallmarks of cancer are introduced and described.
• Specific examples of oncogenes and tumour suppressor genes (like TP53, Rb1 and HER2), and how mutations affect those and relevant mechanisms are outlined.
• Different types of cancer and their origins are presented.
• Understanding the role of the tumour microenvironment in tumorigenesis and the Warburg effect in cancer cells is included.
• The critical role of chromosome segregation, and defects in the processes like chromothripsis in cancer progression are detailed.
• Importance of genetic factors, different types of mutations (driver vs passenger), and their impact are discussed.
• Discussion about precision oncology, including its aims and the latest developments related to the therapeutic field are present.
• A summary of the process and different challenges in delivering effective interventions to patients with cancers are given.

Transcriptomics and Proteomics techniques

• An overview of various methodologies for studying transcriptomes and proteomes.
  • Description of techniques such as SDS-PAGE, 2D-PAGE, and mass spectrometry, and their applications in biomedical research and for diagnosis of diseases.
  • A comparison between healthy and cancer tissues based on proteomics.

PCR

• Polymerase Chain Reaction (PCR) is a method for amplifying DNA sequences.
  • A description of the process through a diagram and a demonstration of how PCR works in a diagrammatic form.
  • Applications of PCR in clinical settings and forensic science.

DNA Sequencing and Precision Medicine

• The principles of DNA sequencing techniques such as Sanger sequencing and Next Generation Sequencing (NGS) are examined, along with their applications in personalized medicine.

Inherited diseases

• Different methods of identifying mutations causing inherited diseases are mentioned and contrasted.
• The types of genetic testing and the methods that are used in laboratory settings, including Sanger sequencing, screening using Next Generation Sequencing and Whole Genome Sequencing (WGS) and Whole Exome Sequencing (WES) techniques are highlighted.
  • An overview of the patients' use of such techniques is given.

Pharmacogenetics or Pharmacogenomics

• The role of pharmacogenomics in optimizing drug dose and predicting medication responses are explained.
  • Examples of clinical applications and limitations of such techniques are shown.

Multifactorial diseases and other traits

• Probability assessment of developing complex diseases (like diabetes, various cancers, obesity) is difficult via sequencing data.
  • Exceptions include examples of genetic variations involved in thrombophilia and Alzheimer's disease, which have clear, direct relationships with their genetic variants.

Further Reading/Resources

• A list of recommended readings, articles, and resources regarding cancer biology, and the genetic bases of clinical diseases.

Test your knowledge on the impact of carrier screening for genetic diseases, focusing on the Ashkenazi Jewish population and the African American community. This quiz also explores key concepts in epidemiology such as disease burden, distribution, and the definition of the field. Challenge yourself with questions that highlight the effectiveness of screening programs and their implications.