PTH241 Introduction to Human Genetics

Course Information

• Course: PTH241 Introduction to Human Genetics
• Instructor: Hanan H. Fouad
• Professor of Medical Biochemistry & Molecular Biology
• Faculty of Physical Therapy, Galala University
• Fall 2024

Intended Learning Outcomes

• Define genetics and understand its applications
• Comprehend the central dogma of molecular biology
• Identify the differences between genes, genome, and chromosomes
• Describe the number, structure, and classification of human chromosomes
• Distinguish crucial scientific terms in genetics
• Explain phases and checkpoints of the cell cycle

Genetics

• Definition: The study of genes, genetic variations, and heredity in organisms.
• Applications: Useful in studying hereditary diseases, cancer, bacteria, viruses, and forensic medicine. Used to produce large quantities of organic molecules (e.g., hormones, antibodies, antibiotics, vaccines) and is important in personalized medicine.

Important Scientific Terms

• Chromosome: Thread-like structure of DNA carrying genetic information.
• Gene: Specific length of DNA with a specific sequence of nucleotides located at a specific locus on a chromosome, and codes for the synthesis of a specific protein.
• Genome: The entire length of the nuclear DNA of an organism.
• Allele: A variety of the same gene with different nucleotide sequences located at the same locus.
  • Dominant alleles: Always expressed in phenotypes.
  • Recessive alleles: Expressed only when dominant alleles aren't present.
  • Homozygous: Having two identical alleles for a gene.
  • Heterozygous: Having two different alleles for a gene.

Genotype vs Phenotype

• Genotype: The genetic constitution of an organism (e.g., AA, Aa, aa), inherited to offspring.
• Phenotype: Observable characteristics (traits) of an organism resulting from interactions between genes and the environment, not inherited to offspring.

Gene Expression

• Central dogma of molecular biology: DNA to RNA to protein.
• Describes the flow of genetic information from DNA to RNA to proteins.
• Proteins carry out all biological or pathological functions of organisms.

Diploid vs Haploid Cells

• Somatic cells: Diploid (2n), containing 23 pairs of chromosomes (22 autosomal, 1 pair of sex chromosomes). Two sets of chromosomes.
• Germ cells (gametes, ovum & sperm): Haploid (1n), containing 22 autosomal chromosomes and one sex chromosome. One set of chromosomes.

Homologous Chromosomes

• A pair of chromosomes - one from each parent.
• Same length, position of the centromere, and the same genes at the same loci.
• Can be genetically different due to different alleles, especially in sex chromosomes (X and Y).

Types of Chromosomes

• Single chromosomes (s-chromosomes): Made from a single DNA molecule.
• Double chromosomes (d-chromosomes): Formed during DNA replication; each chromosome contains two chromatids linked at the centromere.
• Classification by centromere position: Metacentric (middle), submetacentric (slightly off-center), acrocentric (far off-center), and telocentric (at the end).
• Autosomal chromosomes: Paired and carry genes for somatic (body-related) characteristics.
• Sex chromosomes: Differ between male and female, and carry genes for sex characteristics.

Karyotyping

• Karyotype: A laboratory image of an individual's complete set of chromosomes arranged numerically.
• Can be used to look for abnormalities in chromosome number or structure.
• In females, one X chromosome is heterochromatic (Barr body), found attached to the nucleus, and regulates the amount of X-linked gene products.

Human Chromosome Nomenclature

• X-chromosome example: Short and long arms subdivided into regions and bands.

Numbering system of G bands in human chromosomes

• A system for labeling and ordering the chromosome bands

Telomeres

• Repetitive DNA sequences (TTAGGG) at the ends of linear chromosomes.
• Protect ends of chromosomes from damage and fusion with other chromosomes.
• Form 'capped' ends with specialized proteins.
• Prevents genomic instability, cell death or cancer.

Importance of Telomeres

• Prevent chromosome ends from being ligated together.
• Prevent ends from attack by exonucleases.
• Allow repair systems to distinguish true from broken ends.
• Compensate for incomplete replication of linear chromosome ends.

The End Replication Problem

• Telomeres shorten with each cell division.
• Beyond a critical length, cells stop dividing (senescence).
• Telomerase maintains telomeric length in some cells (e.g., germ line, stem cells, cancer cells)

Telomerase enzyme

• An enzyme that maintains telomeric length by extending the 3' end of the lagging strand template.

The Cell Cycle

• The sequence of growth and division of a cell.
• Interphase (G1, S, G2): The cell grows, copies DNA/organelles, and prepares for division.
• Mitosis (Prophase, Metaphase, Anaphase, Telophase): The cell divides.
• Go: A resting phase where cells are not preparing to divide.
• Checkpoints: Control points in the cell cycle to ensure DNA integrity before progression to the next phase.

Assignments

• Mitosis (week 1)
• DNA, RNA structure, types (week 2)
• Replication (week 3)
• Transcription (week 4)
• Translation (week 5)