Introduction to Cytogenetics

Cytogenetics

• Cytogenetics is the study of chromosomes and disease states caused by abnormal chromosome numbers or structures.
• Chromosomes are the containers of hereditary factors, or genes.
• Abnormal chromosome numbers or sizes affect the organism's development.

Fields of Genetics

• Transmission Genetics studies the relationship between gene transmission from parents to offspring and resulting traits.
  • Example: How brown-eyed parents can have a blue-eyed child?
  • Investigates chromosome transmission during cell division and gamete formation
  • Examines common inheritance patterns
• Molecular Genetics investigates the workings of genetic material at the molecular level.
  • Explores chromosome composition and conformation
  • Studies the copying of genetic material
  • Examines gene expression regulation under specific conditions
  • Investigates the molecular nature of mutations
• Population Genetics studies how natural selection leads to allele prevalence in populations.
  • Investigates genetic variation in relation to the environment
  • Examines changes in allele frequencies within populations
  • Analyzes the role of genetics and environment in traits, including quantitative traits like size and weight
• History of the field
  • 1865/1866: Gregor Mendel's work on pea plant inheritance was published
  • 1890: Theodor Boveri suggests chromosomes are involved in inheritance.
  • 1900/1901: Mendel's work rediscovered by De Vries, von Tshermack and Correns.
  • 1902: Sutton and Boveri proposed the chromosome theory of inheritance suggesting chromosomes are involved in inheritance.

Cytological Basis of Heredity

• Prokaryotic Cells are simple, small cells lacking a true nucleus and membrane-bound organelles.
  • Examples include bacteria and blue-green algae
• Eukaryotic Cells have a true nucleus and membrane-bound organelles.
  • Examples include most plants and animals
• Chromosome Shape
  • Prokaryotes: Typically circular
  • Eukaryotes: Typically linear
• Histones (a protein crucial in DNA packaging)
  • Not present in prokaryotes, present in eukaryotes
• Plasmids (extrachromosomal DNA)
  • Sometimes present in prokaryotes, absent in eukaryotes

Cell Structure and Organelles

• Cytoplasm: The main part of the protoplasm containing various organelles.
• Endoplasmic Reticulum: A network of membranes involved in lipid production and protein synthesis.
• Rough ER: Has attached ribosomes
• Smooth ER: Lack attached ribosomes; part of lipid metabolism (catabolism and anabolism)
• Golgi Apparatus: Packages secretory materials, processes proteins, and synthesizes certain polysaccharides and glycolipid.
• Ribosomes: Sites of protein synthesis, found floating in the cytoplasm.
• Mitochondria: Creates cellular energy(ATP)
• Chloroplasts: Photosynthetic organelles in plant cells.
• Centrosomes: The organizing unit for microtubules; crucial for proper cell division.
• Microtubules: A part of the structure of the centrosome essential for the correct formation of spindle fibres.
• Spindle fibers: Involved in the proper movement and segregation of chromosomes during cell division.
• Nucleus: The central control center of the cell, directs cellular activity and inheritance.
• Nucleolus: Located inside the nucleus, site for ribosome manufacture.
• Nuclear envelope: A double membrane surrounding the nucleus with pores for substance exchange with the cytoplasm.

Cell Cycle

• Interphase: The regular and repetitive cycles of processes where cells spend most of their lives. Includes the following phases:
  • G1 phase: Prepares for DNA synthesis. Growth and young cell maturation occurs.
  • S phase: DNA replication occurs.
  • G2 phase: Cell "double-checks" DNA for errors and makes necessary repairs.
• Mitosis Phase: The actual cell division where one parent cell segregates or divides into two daughter cells, which are exact copies. Includes:
  • Prophase: Chromatin condenses into chromosomes.
  • Prometaphase: Nuclear membrane dissolves.
  • Metaphase: Chromosomes align at the metaphase plate.
  • Anaphase: Sister chromatids separate and move to opposite poles.
  • Telophase: Nuclei form and chromosomes decondense.
• Cytokinesis: The cytoplasmic division that produces two daughter cells.

Cell Cycle Checkpoints

• G1/S checkpoint: Prevents cell cycle continuation in damaged or abnormal cells.
• Spindle attachment checkpoint: Ensures spindle fibers attach to all kinetochores before sister chromatids separate.

Mendel's Principles of Inheritance

• Principle of Dominance: One trait (dominant) masks another trait (recessive).
• Law of Segregation: Alleles segregate during gamete formation.
• Law of Independent Assortment: Alleles for different traits segregate independently during gamete formation.
• Dihybrid crosses: Cross between individuals that differ in two observed traits.

Non-Mendelian Inheritance Patterns

• Incomplete Dominance: Heterozygous phenotype is somewhere in between the two homozygous phenotypes.
• Codominance: Heterozygous phenotype shows both homozygous phenotypes
• Pleiotropy: One gene affecting multiple phenotypic effects.
• Epistasis: One gene affecting the expression of another.
• Polygenic Inheritance: Multiple genes contributing to a single phenotypic character.

DNA Replication and DNA Synthesis

• DNA Replication: The process of copying DNA molecules.
• Enzymes: DNA polymerase, Helicase, Ligase... etc are necessary enzymes in this process.
• Leading and lagging strands
• Transcription: DNA to mRNA
• Translation: mRNA to protein

Mutations

• Point mutations: Chemical changes in a single base pair.
  • Substitutions
  • Insertions
  • Deletions
• Frameshift mutations: Insertions or deletions that cause a shift in reading frame and can disrupt downstream protein synthesis.
• Mutagens: Physical or chemical factors that can cause mutations.

Genomics

• Karyotyping: Visual representation of the chromosomes of an individual. Essential for identifying chromosomal abnormalities.

Stem Cells

• Stem cells: Cells with the ability to continuously divide and differentiate into various cell types and tissues.
• Types: Totipotent, pluripotent, multipotent stem cells.
• Applications: Tissue repair, disease treatment, drug discovery, etc.

Genetic Disorders

• Types: single-gene, multifactoral, chromosomal, mitochondrial disorders.
• Examples: Down Syndrome, cystic fibrosis, sickle cell anemia, Huntington's disease.

Gene Therapy

• Methods: Gene insertion, gene replacement, regulatory alteration, gene repair
• Challenges: Viral vector issues, immune response, ethical concerns.

Variation in Chromosome Structure

• Alterations: Deletions, duplications, inversions, translocations.
• Consequences: Health problems and possible sterility.
• Examples: Burkitt lymphoma, folicular lymphoma - chromosomal abnormalities, aneuploidy, monosomy and trisomy