Introduction to Molecular Medicine

Introduction to Molecular Medicine

• Molecular medicine aims to understand disease causes and mechanisms at the molecular level.
• It uses basic research for the prevention, diagnosis, and treatment of diseases and disorders.
• Typical applications are gene therapy, molecular structural analysis, genetic epidemiology, and pharmacology.
• Molecular medicine is a broad field that uses physical, chemical, biological, bioinformatics, and medical techniques.
• These techniques describe molecular structures and mechanisms, identify molecular and genetic errors of disease, and develop molecular interventions.
• The perspective emphasizes cellular and molecular phenomena and interventions.

History of Molecular Medicine

• In November 1949, Linus Pauling, Harvey Itano, and collaborators established the field of molecular medicine with the paper "Sickle Cell Anemia, a Molecular Disease."
• In 1956, Roger J. Williams wrote "Biochemical Individuality," a book about genetics, prevention, and treatment of disease on a molecular basis, now known as individualized or orthomolecular medicine.
• In 1968, a paper by Pauling defined molecular medicine focusing on natural and nutritional substances for treatment and prevention.
• Progress was slow until the 1970s' "biological revolution," which introduced new techniques and commercial applications.

The Human Genome and Molecular Medicine

• A new era in medical intervention is emerging due to advances in genetics and genomics.
• The Human Genome Project has reformed our biological and medical approaches.
• As the genome sequence became powerful, technologies advanced, allowing rapid sequence data acquisition at lower costs.
• Massively parallel sequencing (NextGen sequencing) has ushered genomic and genetic medicine.
• Scientists can now diagnose genetic diseases, identify future disease risks, locate disease modifiers, and predict drug responses.

Impact of the Human Genome Project

• Diagnostics:
  • Identification of genes.
  • For monogenic disorders.
  • For modifying factors.
  • For predisposing risk factors.
  • That change normal cells to cancer cells.
  • For variation in drug response.
• Therapeutics:
  • Identification of new drug targets.
  • Streamlines drug discovery and approval.

Hereditary Factors

• Genes, genetics, and genomics are key to procreation, development, growth, function, and survival
• The health of any living organism is judged by its physical and functional existence.
• Human health depends on its own genetic or genomic constitution, and also on other organisms.
• These include food, shelter, the environment, protection, and transportation.
• Genetics or genomics offers insight and evidence for human diseases.
• These include infectious diseases from lack of protection/failure in controlling microbial infections or parasitic influxes.
• Basic facts about genes, genetics, and genomics and discusses how these impact human health and of plants, crops, and animals necessary for human health and survival.
• Especially relevant to populations in developing countries with limited resources.

Nucleic Acids

• Living organisms divide into eukaryotes and prokaryotes.
• Eukaryotes have compartmentalized internal structure, including a nucleus with algae, fungi, plants, and animals.
• Prokaryotes are single-celled microorganisms microorganisms without a specific part harboring genetic material.
• Viruses are intracellular obligate parasites in eukaryotes and prokaryotes.
• Genetics are transferred via DNA, tightly packaged into chromosomes.
• Prokaryotes usually have a single circular chromosome, eukaryotes have more.
• Humans have 46 chromosomes arranged in 23 pairs.
• Twenty-two pairs are autosomes, and one pair are sex chromosomes (X and Y).
• Females have two X chromosomes (XX), and males have an X and a Y (XY).
• A chromosome consists of coiled DNA and proteins like chromatins.
• DNA has two strands of nucleotide bases of phosphate and sugar: adenine (A), guanine (G) cytosine (C), and thymine (T).
• Base pairing is strict: A pairs with T, and C with G.

Proteins

• Genes are lengths of DNAs that encode the information to make a protein or RNA product.
• RNA differs from DNA: the base thymine (T) is replaced by uracil (U), and the sugar is ribose.
• RNA acts as a template to bring coded information to ribosomes for amino acid assembly into the protein.
• Amino acids are three bases referred to as codons, for a specific amino acid and genetic code.
• Codons located in exons containing coding sequences.
• Exons separate from noncoding sequences of DNA, called introns.
• During transcription, introns get spliced out, and exons attach to mRNA to start protein synthesis.
• Proteins are body's major constituents with variable structures.
• Includes from collagen to hemoglobin to enzymes, hormones, and biological effectors.
• Each protein has peptide chains of amino acids, 20 of which occur in living organisms.
• Structures and functions depend on the order of amino acids by the genetic code.

Genetic and Genomic Variation and Human Disease

• In the 1970s, recombinant DNA technology revolutionized characterizing the molecular basis of human genetic disease.
• This laid the foundation for mapping and deciphering the DNA sequence.
• The goal was to identify all structural and functional genes of the human genome.
• The Human Genome Project (HGP) was, therefore, a natural progression from developments in human genetics.
• The HGP helped map nucleotide sequences of 23,000 nuclear genes composing the human genome.
• HGP provides the basis for “functional genomics”, to explore genomes functional role.
• Understanding how genes and products interact to affect function and influence disease is of great importance.