Human Genetics with Shireef Darwish Course Delivery and Availability Mondays and Thursdays: Two 80-minute lectures in class (AME302) and one lab period on Tuesdays Lea/OMNIVOX: all documents (ppt slides, notes, etc.) will be posted regularly to Lea Office hours: • Mon. 11:30-1:00 • Tues. 10:30-11:30 • Wed. 11:30-12:30 • Thurs. 12:00-1:00, 2:30-4:00 I am always available by MIO (fastest way to get a hold of me) and through the Teams chat function You can ask to arrange meeting time outside of scheduled class through Teams or Zoom Expectations 1. Invest at least 3 hours a week studying lecture material. Much more time will be spent preparing for tests. This is a content-heavy course! 2. Attend all lectures and labs. Quizzes and group work will be a regular occurrence and you must be in attendance to get credited. No make-up work will be given. 3. Participate in and contributing to any/all group work. You will not be credited for just showing up. 4. Engagement during class: ask questions; contribute to class discussions; ask for help when needed; etc. 5. Try to find the answers to your questions by yourself or with the collaboration of a friend/peer. You will learn much more effectively this way as opposed to me simply giving you the answer! EVALUATION Class Tests: • Test 1 15% • Test 2 15% • Test 3 (cumulative) 22.5% Class Quizzes 7.5% Lab Tests (2) 15% (7.5% each) Lab Exercises 10% Project (CA) 15% NOTE: • Class tests will be equal parts multiple choice and written questions • Lab tests will be all written An Introduction to Modern Concepts & Applications of Genetics Learning Outcomes 1. Be able to define genetics and heredity 2. Understand the significance of genetics to the past, present, and future 3. Differentiate between classical, evolutionary, and molecular genetics, and give examples of each 4. State the major goal/achievement of the Human Genome Project 5. Define translational medicine and understand the specific example of PCSK9 • you should be able to write a paragraph summary of the biological role of PCSK9, how different alleles are associated with health outcomes (i.e., hypercholesterolemia), and how this understanding has led to improved medical treatment 6. Be aware of and provide balanced commentary on several bioethical issues centered on modern genetics What is Genetics?! The study of genes, heredity, and variation in living systems. What is Genetics?! 1. Genetics has come to occupy a pivotal position in the entire subject biology. • An understanding of genetics is now essential for any serious student of medicine, evolution, organismal biology, microbiology, biotechnology, etc. 2. Genetics has become central to many aspects of human affairs, particularly medicine and agriculture. Ability to Match Musical Pitch Asparagus Odor Detection Back Hair (available for men only) Bald Spot (available for men only) Bitter Taste Cheek Dimples Cilantro Taste Aversion Cleft Chin Dandruff Earlobe Type Earlobe Type Early Hair Loss (available for men only) Earwax Type Eye Color Fear of Heights Fear of Public Speaking Flat Feet Freckles Hair Thickness Hair Thickness Hair Thickness Ice Cream Flavor Preference Misophonia Mosquito Bite Frequency Motion Sickness Photic Sneeze Reflex Sweet vs. Salty Unibrow Wake-Up Time Widow's Peak COVID-19 & Genetics A phylogenetic tree (recall from NYA!) of the SARSCoV-2 virus showing various genotypes that have evolved through mutation and selection In-Vitro Fertilization IVF is a technique used to help couples conceive • Typically used in cases of infertility • Use to screen for heritable diseases and other genetic conditions (e.g., Down syndrome) • There are approximately 30 fertility clinics in Canada A single sperm being injected directly into an egg cell. Embryos at this stage can be analyzed for genetic disorders before implantation GMOs & Gene Editing Major GMO crops: Three Core Pillars of Genetics i. Classical Genetics (Transmission Genetic) • Q: How are traits passed on from one generation to the next? ii. Evolutionary Genetics • How does variation arise? iii. Molecular Genetics • How do specific molecules – DNA, RNA, and proteins – produce specific phenotypes? Major Pillars of Genetics Classical Genetics i. Classical genetics • focuses on the transmission of phenotypes form parents to offspring. Questions: • How are hereditary diseases transmitted across generations? Major Discoveries: • Mendelian principles of segregation and independent assortment. • Genes are linked to chromosomes, and genes “linked” to the same chromosome segregate together during meiosis. Applications: • Pedigree analysis and probability calculations of disease risk • Gene mapping • Genetic counseling Linkage map of gene alterations in human cancer Changes in average age and market weight for broiler chickens in the U.S. Major Pillars of Genetics Evolutionary Genetics ii. Evolutionary genetics • focuses on the origin and evolution of variation. Questions: • How do new species evolve? • How have changes in our genome led to changes in our behaviour and appearance? • How do genes control development? Major Discoveries: • Genetic code is common across all species. • Genetic basis of biological change over time Applications: • Population genetics (Hardy-Weinberg) • Phylogenetics Molecular Phylogenetics • Comparing DNA sequences is the main approach to investigating evolutionary relationships between different taxa Sequencing of Neanderthal DNA reveals genetic surprise: 1-4% of Eurasian genomes originated in Neanderthals! Major Pillars of Genetics Molecular Genetics iii. Molecular genetics • focuses on the structure and function of DNA, RNA, and proteins. Questions: • How does DNA store and transmit hereditary information? • How do changes in DNA lead to a change in cellular activity? • How do the molecules of heredity interact to give rise to phenotype? Major Discoveries: • Central dogma of molecular biology Applications: • Biotechnology (GMOs, gene editing, personalized medicine, cloning, etc.) • Sequencing and the Human Genome Project • Medical genetics Progeria is a genetic condition characterized by premature aging • We now know it is caused by a mutation in the gene encoding lamin A, a protein that provides structural support for the nucleus. Recombinant DNA technology • Foundation for DNA cloning, genome sequencing, and biotechnology • Applied to medicine, agriculture, and the legal system the Human Genome Project A quest to sequence all 3 billion letters, or base pairs, in the human genome, which is the complete set of DNA in a human cell. • The goal of the HGP was to provide a powerful tool for understanding the genetic factors in human disease, allowing the development of new strategies for their diagnosis, treatment and prevention. Craig Venter (left) & Francis Colins (right) the Human Genome Project Genomics • The sequencing and analysis of genomes. • Interested in gene interactions (e.g., pleiotropy, epistasis, and polygentic traits) and comparisons between different genomes. • A very hot field of science, including emerging fields of synthetic biology and environmental genomics. Logo of the Human Genome Project Alpha Fold 2: Revolution in Predicting Protein Structure • Sequencing a protein is easy • Predicting how that amino acid sequence will fold into its functional 3D shape is one of the hardest problems in biology • Apha Fold 2, an AI developed by Google’s DeepMind, has revolutionized this process the Human Genome Project Applied Translational Medicine: Integrating fields of genetics Translational medicine = Directly translating discoveries in genetics and genomics into new and improved methods of diagnosing and treating disease. • “lab bench-to-bedside” approach the Human Genome Project Applied Translational Medicine: Integrating fields of genetics Q: What’s the leading cause of death worldwide? Approximately 50% of the variation in LDL levels is genetic the Human Genome Project Applied Translational Medicine: Integrating fields of genetics • One gene, PCSK9, has been identified to be a major control of LDL levels Approximately 50% of the variation in LDL levels is genetic the Human Genome Project Applied Translational Medicine: Integrating fields of genetics PCSK9 is discovered and found to control LDL levels in the blood Mutant alleles are discovered that are associated with low levels of LDL High PCSK9 high blood cholesterol Antibodies are developed as a drug to target PCSK9, thus reducing LDL levels the Human Genome Project Applied Translational Medicine: Integrating fields of genetics Bioethics: What Choices Do We Make??? With the completion of the Human Genome Project, and the ability to transfer genes, we are faced with many personal and social decisions • Ethical use of genetic information and biotechnology requires participation by a broad cross section of society. Bioethics: What Choices Do We Make??? Eugenics • Idea developed and promoted by Francis Galton, half-cousin of Darwin • Early 1900s: US attempted to improve the human race using principles of genetics • Ignored effects of environment on behavior • Used by Nazis in Germany to promote genocide Hereditarianism • Idea that human traits are determined solely by genetic inheritance, ignoring environmental effects. • This describes the ‘nature’ side of the ongoing “nature-versus-nurture” debate Eugenics was an influential force in American (and Canadian) life from 1905 through 1933 REVIEW Q: Define the following terms. You should be able explain how they relate to each other: Allele Gene Genome Genotype Phenotype REVIEW Q: Cystic fibrosis and sickle cell anemia are both autosomal recessive traits. What is the probability of having a child with one of those diseases if both parents are carriers for each condition (i.e., they are both heterozygous for CF and SCA)? REVIEW Q: Write out the central dogma of biology: REVIEW Q: Consider the following strand of DNA: 5’ – A T G C G A A C C – 3’ 3’ – T A C G C T T G G – 5’ a) How many phosphodiester bonds are required to form this piece of dsDNA? b) How many hydrogen bonds are present? c) If the lower stand is as the template to transcribe mRNA, how many peptide bonds are present in the polypeptide fragment into which the mRNA is translated?
