“Tales from the genome” (bio110) is intended as an intro level genetics course for non-scientists and science lovers alike. Our vision is to engage you, the student, with real life experiences and reveal how genetics is relevant to you. This course will cover fundamental principles of inheritance, gene expression, development of biological traits, and the acquisition of personal sequence information. Utilizing individual stories from people with a range of visible and hidden genetic traits you will explore important concepts in genetics against a backdrop of real human experiences. After identifying the basis for genetic influence on biological traits you will learn about variation/mutation, environmental influence on gene expression, differences in drug response based on genetics, human ancestry and evolution, as well as the social, legal, and moral questions concerning the knowledge and possession of individual genetic information.
The one overarching theme for the class is to take you on a journey through discerning how genetic information influences various traits and what can be significant in your life. As the course unfolds, you will be able to apply the ideas to your own life, exploring the scientific, social, legal, personal, and moral ideas surrounding the idea of possessing personal genetic information. Using personal stories as backdrops for our lessons, concepts will be covered using interviews, headshots/dialogue, animations, and tablet recordings. Frequent interaction through quizzing (testing knowledge, collecting user information, open-ended interaction) will be utilized to keep you engaged.
By the end of this course, you should have a firm understanding of the very basics of DNA and inheritance, and you should be able to relate to and comprehend news articles concerning personal genetic information. If you are too excited to keep reading further then go get started with Lesson 1!
In this introductory lesson the goal is to provide you with a personally relevant and historical foundation for approaching genetics. The first half of the lesson will focus on the introduction of traits and getting you to think about your own traits and where they come from. Traits will be distinguished among three different categories: physical vs. behavioral, visible vs. hidden, and learned vs. innate. We will briefly introduce five real individuals representing various traits/backgrounds and explain that we will follow their stories and learn about the genetic basis behind their traits throughout the course. The second half of the lesson will focus on historical ideas of heredity, and you will meet three famous thinkers who significantly influenced scientific understanding: Hippocrates, Gregor Mendel, and B.F. Skinner. We will conclude by turning our focus to the hereditary material itself, DNA, and a brief timeline of how far we have come in our understanding. Jump right into the lesson here!
Prepared with a background in thinking about traits and heredity, Lesson 2 will introduce you to the genome, both conceptually and materially. We will begin with the notion that DNA is the ultimate information molecule that makes up our genomes, and we will explore the basics of DNA structure and function. You will then be asked to think about how much DNA comprises a genome, and the lesson will focus on genome size and uniqueness. You will see an interview with Dr. Uta Francke, a human genome expert where she talks about how human genome size was determined and what it means. You will then see how so much DNA fits into a cell: compaction into chromosomes. The second half of the lesson explores the many different sizes and types of chromosomes and how to think about them in the context of the genome. At the end of the lesson you will be asked to define “genome” for yourself. We will close the lesson by wondering how a genome’s information is turned into the flesh and blood of who we are. Jump right into the lesson here!
In this lesson you will build on your concept of the genome as information and begin to learn how the information is literally turned into blood. Using blood type as an example, we will set a scene where blood type is relevant, thus serving as impetus for understanding how our genomes code for different ABO blood types. In this lesson you will learn to differentiate coding vs. non-coding regions of the genome and, after defining a gene, lay the foundation for the central dogma of genetics: DNA--(transcription)-->RNA--(translation)-->Protein. You will learn how the DNA is transcribed, how introns are spliced out and exons spliced together in a mature mRNA, and how mRNA codons are translated by ribosomes into amino acids via the genetic code. Consequences of variation in these coding regions will be discussed in the context of blood type. The lesson will close with resolution of the blood type story based on information from the genome. You will also see two expert interviews: (1) Dr. Uta Francke discusses genome coding regions, and (2) Dr. Jane Chueh reveals the importance of blood type in the clinical setting. Jump right into the lesson here!
Your focus in this lesson will be on non-coding regions of the genome. With the aim of learning how genes are turned on and off, we will use lactase persistence (affecting lactose intolerance) as an example of a trait where variation in non-coding regions affects whether a person can digest dairy products or not. We will delve into the cause of the trait at the molecular level and introduce the idea that without the protein necessary to digest lactose, called lactase, an individual suffers symptoms such as abdominal bloating and cramps, flatulence, diarrhea, nausea, and even vomiting. As a baby everyone makes lactase, but as they grow older some people turn off their lactase gene and others do not. This story will be used to introduce the concept of gene regulation, focusing on the idea of a promoter and transcription factors, as well as consensus sequences. Consequences of variation in non-coding regions will be discussed. An interview with a trait representative, Ryan Salvadore, will reveal what it is like to live with lactose intolerance. You will also learn that most gene regulation is complex, and combinatorial regulation using both enhancers and silencers is essential to achieve particular thresholds of expression for various genes. At the end of the lesson an interview with an expert on lactose intolerance, Dr. Bill Durham, will reveal an amazing evolution of this trait in humans. Jump right into the lesson here!
This is likely to be the most challenging lesson in the whole course. In this lesson you will focus on how traits and the genetic material that causes them are passed on from parent to offspring. You will learn about pedigrees and how they are used to track traits in related individuals. Three major inheritance patterns will be covered: autosomal, sex-linked, and maternal inheritance. You will also learn the most basic example of how some alleles can be either dominant or recessive. You will then look at how the genetic information is tracked in these pedigrees and expressed in terms of traits. We use a few case studies to illustrate different types of inheritance patterns. An interview with trait representative Ginny Foos will reveal what it is like to live with the dominant trait achondroplasia, the most common cause of dwarfism. Ginny’s discussion of passing this trait down to her children will spark ideas about how the hereditary material is passed through the germline. You will learn about cell division (mitosis and meiosis) and the consequences of each. The process of recombination will explain how various alleles can be mixed and matched before being passed down to your offspring (one of the most complicated subjects for beginners). We will cover other important concepts like independent assortment, the law of segregation, punnett squares, inbreeding, and more. After using examples of autosomal inheritance, we’ll describe sex-linked inheritance and mitochondrial inheritance. An interview with trait representative Geoff Donaker will reveal what it is like to live with X-linked Red-Green color blindness. The lesson will progress from a simplified explanation of chromosome segregation to an exploration of gene alleles and the relationship between genotype (genes) and phenotype (traits). You will even see an interview with Kelly Chen, a genetic counselor. By the end of this lesson you will be set up to more fully understand your genetic information (covered more in Lesson 7) and how it relates to genetic conditions (covered more in Lessons 8 and 9). Jump right into the lesson here!
The focus of this lesson is about various alleles in a population that spread from an original mutation. But where do these mutations come from? In this lesson you will begin to understand how mutations occur, what common mutations are, and how they spread in the population. There are several kinds of mutations that can be either spontaneous (replication errors) or induced (damaging radiation). You will learn about silent, missense, nonsense, and frameshift mutations that occur in DNA coding regions. You will also learn about SNVs, deletions, insertions, duplications, and chromosomal translocations. One of our real-world examples to use here is skin pigmentation when talking about protection from UV rays. Not only does skin pigmentation protect from damaging UV rays, but the evolution of lighter skin pigmentations occurred as a result of changes in the coding regions of genes that affect melanin deposition in the skin. An interview with trait representative Kagure Kabue will describe what it’s like to live with dark skin pigmentation. Consequences of these mutations will be discussed as well as their transmission and maintenance in a population through natural or random selection and fluctuation of allelic frequencies. The end of the lesson will ask you to evaluate a real world story about the evolution of HIV resistance due to genetic variants of the CCR5 gene. Additionally, expert interviewee Dr. Uta Francke discusses human genetic variation. Jump right into the lesson here!
By this point you have learned the basics of how genetic information is manifested into traits and how variation arises from mutation. Now it’s time to think about obtaining total personal genetic information for an individual and figuring out how to interpret it. We will revisit our five individuals who are trait representatives and ask them questions about their motivations for wanting (or not wanting) to have more information on their known and unknown traits. Dr. Joanna Mountain, Senior Director of Research at 23andMe, is co-instructor for this lesson. She guides us through the process of delivering a saliva sample to the lab. You will then see a series of interviews with technical expert and 23andMe co-founder Dr. Brian Naughton who will explain the major steps of DNA extraction, DNA amplification, chip hybridization, and initial data analysis. Once the sample results are ready, you will be guided through ancestry and health results that a company like 23andMe offers. We will close this lesson thinking about the ethical implications of knowing this information and wondering what more you can learn about other traits based on this knowledge. Jump right into the lesson here!
Given the tools available to modern geneticists we can now begin to unravel the genetic foundations underlying certain conditions and traits. In this lesson, you will explore the simplest genetic conditions where changes in a single gene or genetic factor are sufficient to result in a detectable phenotype. New molecular terminology will be introduced to understand gain-of-function and loss-of-function alleles that cause red-green color blindness, achondroplasia, osteogenesis imperfecta, and sickle cell anemia. We will talk to several people who are living with these genetic conditions. The scientific, medical, and societal implications of these traits will be explored as well. An interview with trait representative Geoff Donaker will reveal more about what it is like to live with red-green color blindness. Trait representative Ginny Foos is interviewed about what it is like to live with achondroplasia, the most common cause of dwarfism. An interview with Kagure Kabue will discuss the incidence of sickle cell anemia in her native Kenya, and she will talk about what it’s like to have Malaria, one of the main reasons sickle cell is prevalent in sub-Saharan Africa. Jump right into the lesson here!
This lesson will begin with the idea that most traits cannot be explained by one gene. Many traits are controlled by many genes, with an environmental component too, which can make figuring out the genetic component even harder. You will start with a personal story from trait representative Carole Kushnir who describes what it is like to be diagnosed with a genetic variant that predisposes her to a higher risk of breast/ovarian cancer. We will discuss the two ways we categorize complex traits: quantitative or qualitative. The idea of traits with an unknown genetic component will be explored (using the example of bipolar disorder), focusing on ways to discern genetic heritability (twin studies) and which genes could possibly be causing a trait (Genome Wide Association studies). An interview with Nikolas Blanchet will reveal what it is like to live with Bipolar II Disorder. The lesson will close emphasizing the importance of understanding that genetic risk for complex traits is not genetic determinism, but there is a “missing heritability” for many multifactorial traits. The example of type 2 diabetes will be used to demonstrate this point, and your final evaluation will be on this topic. Jump right into the lesson here!
One major way we interact with our environment is through what we ingest and must be metabolized. Generally speaking anything in this category counts as a drug, and one person’s reaction to a drug may be different from another’s depending on their genetic makeup. This lesson will begin by using alcohol as an example and showing how some people have very little tolerance due to variation in their genome. An interview with Jennie Kim will explore what it is like to live with alcohol flush reaction. We will use this as a jumping off point to cover the basics of pharmacogenetics, including pharmacodynamics and pharmacokinetics. You will explore how genetics affects these aspects of pharmacology and then interview Dr. Russ Altman who’s developing one of the web’s best sources of pharmacogenomics data: PharmGKB. Warfarin dosing will be used as the main example to demonstrate how the environment and genetic variants affect drug response and will alter how a physician makes a prescription. An interview with trait representative Franklin Kalk will reveal how important it is to get the right dose of Warfarin. The lesson will end by discussing the possibility of tailored drugs that maximize efficacy and minimize toxicity based on your specific genotype. Jump right into the lesson here!
This lesson is a capstone lesson with regards to understanding how we can use accumulated genetic information across populations to piece together our ancestry and evolution. A big overarching theme will be our common relation to all humans on the planet. Knowing what we know about variation, the question is how to track this variation among different groups. You will meet our trait representative Sterling Tadlock who was adopted at birth and wants to find out more about his genetic background. Using information from autosomes as well as Y and mitochondrial chromosomes, you will learn how SNV sampling is used in conjunction with IBS and IBD scores to trace an individual’s ancestry. You will follow Sterling’s story and discover his genetic background as well as his maternal and paternal lines. We will interview a computational biologist, Dr. Eric Durand, who developed the IBD scoring method at 23andMe. We will also interview CeCe Moore, a genetic genealogist, who describes how to build a family tree using known genetic relationships. You will have a chance to explore our shared deep ancestry with chimpanzees, the early human expansion out of Africa, and the result of population bottlenecks during migration. The lesson will end by considering the profound impact of our inter-relatedness, and how there must be many social implications about having this information and what we can do with it. Jump right into the lesson here!
This last lesson will bring our discussion of traits and genomes into the fold of social implications and professional development. You will begin with the amazing story of Henrietta Lacks and how cultural and institutional failures resulted in what is considered by most to be an ethical misstep. We will interview a bioethicist who explains how far we’ve come and what has shaped our thinking about topics from genetic discrimination to gene patenting. Our group of five will be asked multiple questions about what it means to have this information, the social stigma surrounding it, and whether they’ll be better off for knowing it. This will transition into understanding how genetic information can be used in various careers. You will have access to six interviews of individuals who use genetic information in their professional lives on a regular basis: bioethicist/biolegal expert (Rachel Zuraw), computational biologist (Dr. Eric Durand), director of clinical operations (Sascha Ellers), genetic genealogist (CeCe Moore), genetic counselor (Kelly Chen), and human geneticist (Dr. Uta Francke). You will explore what it’s like to have their job and answer the kinds of questions they deal with. Jump right into the lesson here!