Genetics Overview and Mutation Types

Embryonic Stem Cells

• Totipotent: Capable of differentiating into any type of cell.

Somatic Cells

• 46 chromosomes
• Diploid
• Mitosis

Gametes

• 23 chromosomes
• Haploid
• Meiosis

DNA Structure

• 4 nitrogenous bases: Adenosine, Guanine, Cytosine, Thymine
• Adenosine and Guanine – Purines
• Cytosine and Thymine – Pyrimidines
• Phosphate molecule
• Double helix
• Always has 3 base pairs

Mutation

• Inherited alteration of genetic material
• Chromosome aberrations
• Mutation hot spots

Single Gene Mutation Types

• Base pair substitution:
  • Silent: Replaces base but no change in amino acid.
  • Missense: Different amino acid produced.
  • Nonsense: Codes for premature stop codon.
• Frameshift mutation: Insertion or deletion of base pairs not in multiples of 3 (codons).
  • Frameshift changes the reading frame.
  • Inframe: Insertion/deletion in multiples of 3, no frameshift.

Mutagens

• Agents that increase mutation frequency (teratogens).
• Examples: Radiation, chemicals (nitrogen mustard, vinyl chloride, formaldehyde).
• Affect the developing fetus after 2 weeks of implantation.

Genetic Terms

• Locus: Gene's position on a chromosome.
• Allele: Different form of a gene at a given locus.
• Polymorphism: Locus with two or more alleles at appreciable frequency.
• Heterozygous: Different alleles (Bb).
• Homozygous: Identical alleles (bb).
• Genotype: Gene composition at a specific locus.
• Phenotype: Outward appearance.
• Penetrance: Percentage of individuals with a genotype expressing the phenotype.
  • Incomplete penetrance: Individuals with the gene but not expressing the disease.
• Expressivity: Extent of phenotype variation with a particular genotype.
  • Caused by modifier genes, environmental factors, different mutations.
• Pedigrees: Family tree showing genetic disease tracking.
  • Types of disorders:
    • Single gene
    • Chromosomal
    • Multifactorial

Autosomal Dominant Inheritance

• Single gene defect
• No generational skipping
• Affected offspring can have a normal or heterozygous parent.
• Allele can be disease-causing or normal.
• Recurrence risk for offspring is 50%.

Autosomal Recessive Inheritance

• Single gene defect
• Both parents need to contribute the affected allele.
• Skips generations.
• Parents of affected children are typically heterozygous carriers.
• Recurrence risk is 25%
• Consanguinity (inbreeding) increases risk.

Sex-Linked Inheritance (X-linked)

• Mostly affects males.
• Examples: Duchenne muscular dystrophy.
• Characteristics:
  • More males than females affected.
  • Fathers pass it to daughters but not sons.
  • Can skip generations.
• Most X-linked disorders are recessive.
• Sons of female carriers have a 50% risk of being affected.

Chromosome Disorders

• Autosomes (first 22 pairs), homologous.
• Sex chromosomes.
• Karyotype/karyogram: Chromosome picture.
• Chromosome aberrations:
  • Euploid: Multiple of normal chromosome number (diploid/haploid).
• Polyploid: More than diploid number of chromosomes.
  • Triploidy (3 copies, 69 chromosomes)
  • Tetraploidy (4 copies, 92 chromosomes) – Not compatible with life.
• Aneuploidy: Not a multiple of 23.
  • Trisomy (3 copies)
  • Monosomy (1 copy)
  • Nondisjunction: Failure of homologous chromosome/sister chromatids to separate in meiosis/mitosis.
    • Usual cause of aneuploidy.
  • Autosomal aneuploidy: Examples: Down syndrome (trisomy 21), Cri-du-chat syndrome, Fragile X syndrome
• Partial trisomy: Only a portion of a chromosome is extra (ex. Down's Syndrome - trisomy 21)

Multifactorial Genetic Disorders

• Polygenic traits: Variations caused by several loci.
• Multifactorial traits: Genetic and environmental factors influencing the trait.
• Threshold of liability: Certain level of risk factors needed for a disorder to occur.

Epigenetics

• Biological mechanisms that turn genes on or off.
• Mechanisms:
  • DNA methylation
  • Histone modification (acetylation/deacetylation)
• Chromatin: DNA association with histones that affects gene expression.

RNA Based Mechanisms

• Noncoding RNA (ncRNA) roles in RNA splicing, DNA replication, and RNA interaction.
• MicroRNAs (miRNA): Modulate mRNA stability and translation.
  • Oncomirs: miRNAs stimulating cancer.

This quiz covers the fundamental concepts of genetics, including embryonic stem cells, the structure of DNA, and various types of mutations. You'll explore somatic cells, gametes, and the impact of mutagens on genetic material. Test your knowledge on the mechanisms and implications of genetic mutations.