Chromosome Structure, DNA, and RNA

• Basics of Genetics presented by Dr. Sim M. Simolde, Assistant Professor, College of Medicine, College of Allied Medical Sciences, Cebu Doctors' University.

Cell Hierarchy

• Atom combines with other to molecules
• Molecules combine to form cells
• Cells combine to form Tissues
• Tissues combine to form Organs
• Organs combine to form Organ Systems
• Organ Systems combine to form an Organism

Chromosomes

• Chromosomes are found in the nucleus of cells.
• Chromosomes are thread-like structures that carry genetic information from cell to cell.
• Chromosomes are passed down from parents to their offspring.
• Humans have 23 pairs of chromosomes.
• 22 pairs of autosomes.
• 1 pair of sex chromosomes.

Chromosome Anatomy

• P arm: the short arm structure of a chromosome.
• Q arm: the long arm structure of a chromosome.
• Centromere: constricted region that controls chromosome segregation at mitosis and meiosis.
• Telomere: region of repetitive DNA sequences at the end of a chromosome, that prevents the ends of chromosomes from tangling.
• There are 2 identical chromatids, one being an exact copy of the other.
• Chromatids form during the synthesis (S) phase of the cell cycle
• Each chromatid contains one DNA molecule

Chromatin

• Metaphase chromosomes: highly condensed and visible during cell division (1400 nM)
• Chromatin fiber: a more relaxed state of DNA (700 nM)
• Nucleosomes: DNA wrapped around histone proteins (30 nM)
• DNA( 2nM)

Nucleosomes

• Nucleosomes contains Nucleic acid
• Histones are the most abundant chromatin protein.
• Histones are rich in arginine and lysine.
• Histones divide into two main types: core histones and linker histones.
• Core Histones: Composed of pairs of H2A, H2B, H3, and H4, they form a histone octamer.
• Linker Histones: H1 is found in the linker region, loosely bound to the nucleosome.

Nucleic Acids

• Nucleic acids are composed of: a sugar (pentose), a nitrogenous base, and a phosphate group.

Sugars (Pentose)

• C1 attaches to the Nitrogenus Base
• C2 attaches to either -H or -OH
• C3 attaches to -OH
• C4 exist as is
• C5 attaches to a Phosphate group

Nitrogenous Bases

• Purines: adenine and guanine (Heterocyclic rings)
• Pyrimidines: cytosine, uracil (RNA), and thymine (Single ring)
• "PURE As Gold" is a mnemonic do to the fact that Purines are Adenine and Guanine.
• "CUT the PY (pie)" is a mnemonic do to the fact that Cytosine, Uracil and Thymine are pyrimidines.

Phosphate Group

• The phosphate group is negatively charged
• Attached to C5

Nucleosides

• Sugar + Nitrogenous base yields a Nucleoside
• Adding Adenine to Ribose = Adenosine
• Adding Guanine to Ribose = Guanosine
• Adding Thymine to Deoxyribose = Deoxythymidine

Nucleotides

• Nucleoside + a Phosphate group yields a Nucleotide
• Adenosine + a Phosphate group can yield AMP, ADP or ATP

Nucleotide Table

• Adenine (Base) + Deoxyribose (Pentose) - D-Adenosine (Nucleoside) - D-Adenosine monophosphate (Nucleotide + 1 PO)
• Guanine (Base) + Deoxyribose (Pentose) - D-Guanosine (Nucleoside) - D-Guanosine monophosphate (Nucleotide + 1 PO)
• Cytosine (Base) + Deoxyribose (Pentose) - D-Cytidine (Nucleoside) - D-Cytidine monophosphate (Nucleotide + 1 PO)
• Thymine (Base) + Deoxyribose (Pentose) - D-Thymidine (Nucleoside) - D-Thymidine monophosphate (Nucleotide + 1 PO)
• Adenine (Base) + Ribose (Pentose) - Adenosine (Nucleoside) - Adenosine monophosphate (Nucleotide + 1 PO)
• Guanine (Base) + Ribose (Pentose) - Guanosine (Nucleoside) - Guanosine monophosphate (Nucleotide + 1 PO)
• Cytosine (Base) + Ribose (Pentose) - Cytidine (Nucleoside) - Cytidine monophosphate (Nucleotide + 1 PO)
• Uracil (Base) + Ribose (Pentose) - Uridine (Nucleoside) - Uridine monophosphate (Nucleotide + 1 PO)

Functions of Nucleotides

• Building blocks of nucleic acid
• Carriers of activated intermediates of CHO, CHON, and FATS
• Structural components of coenzymes
• Second messengers in signal transduction pathways
• Principal biologic transducer of free energy
• Regulatory compounds of pathways in intermediary metabolism
• Synthetic analogs used as drugs.

Complementarity base pairs

• Adenine (A) pairs with Thymine (T)
• Guanine (G) pairs with Cytosine (C)
• A-T pairs have 2 hydrogen bonds
• G-C pairs have 3 hydrogen bonds
• extremes of heat, pH, and destabilizing agents denature hydrogen bonds
• Stable at pH 4-9 and disrupted by formamide.
• G-C base pairs require more energy to disrupt than A-T base pairs

Antiparallel Arrangement

• Sugar Phosphate backbone
• Phosphodiester bonds: Covalent bond formed by phosphorus and oxygen atoms creating a stable linkage.

DNA and Chromosomes

• Chromosomes are at the top, they consist of coils referred to as Supercoils, which make up a Nucleosome, which are comprised Histones and DNA double helix

Deoxyribonucleic acid (DNA)

• The length of a fully extended eukaryotic molecule is 3 m per genome
• Contain the genetic information of an organism, packaged in chromatin using histones and organized into chromosomes
• Located in the nucleus in eukaryotes and in the nucleoid region of the cytosol in prokaryotes

Ribonucleic acid (RNA)

• Single stranded molecule
• Has a ribose sugar containing a hydroxyl group at the 2' position
• Thymine is replaced by the methylated uracil
• Susceptible to alkaline hydrolysis
• Rapidly degraded by RNA-specific enzymes

Comparison of Key Features of DNA and RNA

Number of Chromosomes

• 46 chromosomes is equal to 46 chromatin
• 46 chromosomes is equal to 92 chromatin

When are Chromosomes Visualized?

• During the cell cycle.
• Structures within Nucleus: Nuclear membrane, Nucleoplasm, and Nucleolus.
• Types of Chromatin: Euchromatin and Hetero-chromatin.

Euchromatin vs Heterochromatin

Cell Cycle

• A cell goes though a series of stages
• Divided between Interphase and Mitosis sections
• Interphase itself consists of G1, S phase, and G2
• Mitosis consist of: Prophase, Prometaphase, Metaphase, Anaphase, Telophase

Interphase

• Interval between cell divisions
• Divided into 3 phases: Gap 1 (G1), Synthesis (S), and Gap 2 (G2)
• Chromatin is in a relaxed state

Types of Somatic Cells

Prophase

• First phase in Mitosis, considered half of mitosis on it's own
• Key events: Migration of two centrioles, Organization of microtubules, Nuclear envelope breakdown Nucleolus disintegrates, and Chromatin fibers condense

Metaphase

• In metaphase Chromosomes migrate to the equatorial plane/metaphase plate
• Key events: Binding of the spindle fibers to the chromosome kinetochore, degradation of cohesin by enzyme separase, and sister chromatid arms disjoin except at the centromere
• Kinetochore: Protein within centromere where spindle fibers attach
• Cohesin Holds sister chromatin together
• Shugoshin Prevents cohesin from being degraded by separase

Anaphase

• Shortest stage of mitosis
• The disjunction of sister chromatids phase
• Degradation of shugoshin
• Sister chromatids of each chromosome are pulled toward the opposite poles of the cell

Telophase

• Telophase considered the final stage of mitosis
• Events that happen: Formation of cleavage furrow. Cytokinesis, the Cytoplasm loosens

Meiosis

• Reductional division
• Produces gametes
• Involves 2 successive cell divisions
• Produces 4 haploid (n) daughter cells
• Each daughter cell is genetically different
• genetic exchange between a homologous pair of chromosomes.

DNA Repair

• DNA Repair halts after Unreplicated or Damaged DNA at G2, S and G1 phase
• DNA Repair halt after Chromosome Misalignmentat M phase

DNA Repair - Checkpoints

• G2/M checkpoint: NHEJ, BER, HR repair.
• G1/S checkpoint: NHEJ, BER, NER repair.
• At phase S: MMR, NHEJ, BER, HR repair.

Mutations

• Any permanent change in DNA base sequence
• Physical, biochemical, or by mutagens
• Can potentially change the mRNA sequence & AA sequence
• Common mutations include the following: point mutations and frameshift mutations (insertion or deletion).
• Other mutations: Large segment deletion, Splice donor or acceptor, Triple repeat expansion

Point Mutation

• Transition, changes in the DNA sequence
• Purine to purine / Pyrimidine to pyrimidine
• Transversion, change by vice versa
• Purine to pyrimidine or vice versa

Point Mutation types

Frameshift Mutation

When a DNA sequence is altered by insertion or deletion of one or more nucleotides, NOT a multiple of three

Genetics Terminology

• Gene: Functional unit of inheritance
• Gene: composed of a sequence of nucleotides and codes for a product (RNA or protein)
• Locus: Position of a gene in a chromosome
• Allele: Alternative form of a gene in the same locus

Genetics Terminology

• Homozygous: Alleles are the same (TT, tt)
• Heterozygous: Alleles are different (Tt)

Autosomal Dominant

• One dominant allele is enough to produce a phenotype.
• only One parent is usually affected.

Autosomal Dominant Diseases

Autosomal Recessive

• Two recessive alleles needed produce a phenotype
• 25% express disease, 50% carrier, 25% normal

Autosomal Recessive Diseases

X- LINKED DOMINANT (XD)

• In a cross of heterozygous female with a normal male:
  • 50% of sons and 50% of daughters will have the disease
• In a cross of affected male with a normal female:
  • 100% of daughters with disease, 0% of sons with disease

X LINKED DOMINANT Diseases

X LINKED RECESSIVE

• Usually males express phenotype (due to homozygosity for the allele)
• Affected males do not transmit the disease to their sons, but all of their daughters are carriers
• In a cross of heterozygous female and affected male:
  • SONS: 50% (+) disease, 50% (-) disease
  • DAUGHTERS: 50% (+) disease, 50% carrier

X LINKED RECESSIVE Diseases

Quiz questions covering fundamental concepts in genetics, focusing on chromosome structure, the functions of DNA components like telomeres, and the characteristics of RNA. Questions also explore chromosome behavior during cell division.