BIOL 205 Week 1 Notes PDF

BIOL 205 Mendelian and Molecular Genetics Week 1: Introduction to BIOL 205 Go over course website and course outline Expectations and how to think about genetics Get a feeling for the class demographic Genetics Timeline Using Genetics to understand function Mut...

BIOL 205 Mendelian and Molecular Genetics Week 1: Introduction to BIOL 205 Go over course website and course outline Expectations and how to think about genetics Get a feeling for the class demographic Genetics Timeline Using Genetics to understand function Mutants and Mutation DNA as the genetic information Importance of Genetic Variation and Gene Regulation Genetic terms you must know Forward vs. Reverse Genetics Methods used in genetics Genetics Today Model organisms BIOL 205 Dr. Chin-Sang's Lectures  Instructors: Dr. Ian Chin-Sang (course coordinator), Rm. 2422a Biosciences complex, 533-6124 Email: [email protected] Dr. William Bendena, Rm. 2445 Biosciences complex. 533-6121 Email: [email protected] Tutorial Coordinator: Dr. Howard Teresinski, Email: [email protected] Contact your assigned TAs in your section  Got Questions about Tutorial material? Ask your TA or Tutorial Coordinator: Dr. Howard Teresinski [email protected] 3 About Me B.Sc. 1986-1991 University of Waterloo, Waterloo, ON, Canada Honors Biology (Co-operative program) Ph.D. 1991-1997 Department of Molecular and Medical Genetics, University of Toronto, Toronto, ON Canada Developmental Biology and Genetics (Sex Determination in C. elegans) Post Doctoral Fellow 1997 – 2001 Department of Biology, University of California Santa Cruz, Santa Cruz, CA, USA The study of Eph/Ephrin Signaling in C. elegans morphogenesis. Professor July 1st 2001 – Present Department of Biology, Queen’s University, Kingston, ON, Canada C. elegans Developmental Genetics 4  Course website: hosted through onQ BIOL 205 Mendelian and Molecular Genetics Course Description: An introduction to Mendelian and molecular genetics covering the basic mechanisms of genetic transmission, gene structure and function, as well as the application of molecular genetics in medicine and biotechnology. PREREQUISITE BIOL 102* and BIOL 103*.  Introduction to genetic analysis 12th edition by Anthony Griffiths et al. Purchase at campus bookstore. “Achieve Learning” web companion comes with the e-textbook. Textbook: Can I use another textbook? Yes and use the Internet and AI Cool web links related to lecture material It’s like having a tutor tireless and with patience 24/7. However, considering the performance of ChatGPT with an accuracy around 70% it should be noted that this tutor is still fallible and there is room for improvement.  Course Grades*: Lecture Quizzes: 10% Midterm Exam: 30% Tutorials: 30% Final Exam: 30% *A final letter grade is given using Queen’s University conversion table  Please Do Not post material from this course on other websites A reminder to all: The material on this website is copyrighted and is for the sole use of students registered in BIOL 205. The material on this website may be downloaded for a registered student’s personal use, but shall not be distributed or disseminated to anyone other than students registered in BIOL 205 (This means no posting lecture notes, quizzes, exams etc. to other websites.) Failure to abide by these conditions is a breach of copyright, and may also constitute a breach of academic integrity under the University Senate’s Academic Integrity Policy Statement. Course Goals: Make introduction to genetics fun and exciting. Give you the the fundamentals of Genetics. Not to overload you with too much information. Need extra help? I am available to will meet with you. Make an appointment by e-mail. If you’re stuck: 1) Try to solve the problem yourself. Google is your friend. 2) Ask your fellow classmates- use the Biol 205 online forum*. 3) Ask your TAs 4) Make an appointment. *Those who participate in the online forum will get bumped from 79 to 80 or 89 to 90. Why do people hate genetics? Is it too difficult to understand? Is it boring? Is it not relevant? Why you should love genetics: We live in a “post-genomics” world— Common to see news related issues based on genetics What does it mean when someone says “you have your father’s nose?” Covid-19 mRNA vaccine Molecular genetics has revolutionized agriculture and the pharmaceutical industry. Genetic testing, forensics, and treatment of genetic diseases. Eg. Cancer and personalized medication. Companies focusing on personalized genetics eg. 23 and Me I guarantee that in the near future it will be routine to have your genome sequenced and this information will be used for medications and lifestyle choices. You can do some really cool stuff! Talking mice, Opiate production in yeast, Plant lights, CRISPR Cas9, Queen’s iGEM 13  The New York Times May 14 2013 “the decision to have a mastectomy was not easy” Angelina Jolie BRCA1 mutation Myriad Genetics patent March 2015: Ovaries removed ? Tracing the origin of a new point mutation The number of new point mutations increases with father’s age 2013 The engineered “ re y petunia” emits a continuous green glow thanks to genes from a light-up mushroom 19 fi fl CRISPR/Cas9 Genome Editing Potential to cure many single gene genetic diseases. eg. Cystic Fibrosis Muscular Dystrophy Huntington’s Disease Sickle Cell Genetic enhancements? Venture capitalist have poured millions of dollars in many start up companies 20 http://qgemteam.com The International Genetically Engineered Machine competition (iGEM) is the premiere undergraduate Synthetic Biology competition. “I understood all the material but still did poorly on the exam, how come?” How to do well in BIOL 205: Attend lectures, listen and think. Ask questions when in doubt. Process the material during lecture. Read the assigned readings in the textbook. Do the assigned problems. Study even when you don't have a test. We will use “Quizizz” to carry out Polls https://quizizz.com or joinmyquiz.com We live in an Age of Genetics Genetics has a long and fascinating history: Mendel’s 1866 paper to.. Present day genomics Many Nobel Prizes have been awarded for Genetics research. Key Events in the History of Genetics (Part 1) Key Events in the History of Genetics (Part 2) "This is an actual photo of a genetically engineered mouse with a human ear on its back". Oct. 11, 1999 New York Times Ad. Turning Point Project No Genetic engineering involved in creating this mouse (search “Vacanti Mouse”)  Scientific Method 1. Observation 2. Hypothesis 3. Experimentation to test hypothesis 4. Analyze results: Accept or Reject the Hypothesis The scientific method helps to minimize the influence of bias or prejudice in the experimenter. Mutants Wild type Mutant eyeless (pax-6) The eyeless mutant will help you understand which biological process? This was the first question on the 2008 mid-term exam. A. Sight B. Eye formation C. Eye colour determination D. Transcription BIOL 205 Dr. Chin-Sang's Lectures Wild type Mutant eyeless (pax-6) pax-6 (eyeless) mutations in mouse and humans cause absence of eyes Glaser et al. Nature Genetics 7, 463 - 471 (1994) BIOL 205 Dr. Chin-Sang's Lectures Ectopic eye production from the eyeless gene “eyes” http://www.biozentrum.unibas.ch/Research/Cell_Biology/Gehring/Pictures/pictures.html BIOL 205 Dr. Chin-Sang's Lectures  Cells function Like a Rube Goldberg Machine "accomplishing by extremely complex, roundabout means what BIOL 205 Dr. Chin-Sang's Lectures seemingly could be done simply." Like begets like Genetics BIOL 205 Dr. Chin-Sang's Lectures Corn will give rise to corn Mice will give rise to mice Humans give rise to humans Therefore the fertilized egg contains information that specifies the sequence of developmental instructions to make an organism William Bateson gave genetics its name The rediscovery of Mendelism and the birth of the genetics revolution, 1904 Genetics—the study of inheritance. Bateson, 1904. Typical Eukaryotic Gene Structure and Products Promoter Coding region 5’ UTR Exon 1 Exon 2 Exon 3 3’ UTR 5’ Intron 1 Intron 2 3’ DNA Transcription and Splicing AAAAA mRNA Translation Protein BIOL 205 Dr. Chin-Sang's Lectures Genes have regulatory and coding regions Historically, genes were identified by mutation— If you saw a fly dancing on its head, would you keep it? Genetic analysis, using organisms with mutations is a powerful method for investigating biochemical, physiological and developmental pathways. Today the vast majority of genes are identified by sequencing and computer programs. Large scale DNA sequencing allow evolutionary biologist to compare entire genome of species and determine what changes there are between a man and a mouse (surprisingly very few) BIOL 205 Dr. Chin-Sang's Lectures  The passage of genetic information must have four properties: 1. Diversity of structure: There must be information for the differences in cellular structures. 2. Ability to replicate: There must be some mechanism for replication so information can be passed from generation to generation. 3. Mutability: Information must be able to change. 4. Translation: A blueprint is not enough. You need the machinery to read and translate the information to build the structure. BIOL 205 Dr. Chin-Sang's Lectures  The structure of DNA DNA is composed of two nucleotide chains held together by complementary paring of A with T and of G with C.  DNA has the four properties that characterize genetic information 1. Diversity of structure , 2. ability to replicate, 3. mutability, 4. translation 1. Diversity of structure: only 4 nucleotides can lead to many combinations: 4n where n is the number of base pairs A sequence o 4 bp would have 4X4X4X4= 256 combinations A sequence of 10 bp would have 410= 1,048,576 different combinations. Human genome 3 billion base pairs 43 billion = a very large number 2. Ability to replicate: DNA is replicated by unwinding of the two strands of the double helix and the building up of a new complementary strand on each of the separated strand of the original double helix.: “It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material” Watson and Crick April 25th 1953 in the journal Nature 3. Mutability: In the course of replication an incorrect base may be put in or bases may be lost or duplicated. Since each strand serves as a template the new mutation would be transferred to subsequent copies. 4. Translation into form and function: The sequences of A,T,C,and G must be used by the cell to create protein molecules having a particular amino acid sequence. Transcription and Protein Translation. During transcription, one of the DNA strands of a gene acts as a template for the synthesis of a complementary RNA molecule  Protein Translation: The production of a chain of amino acids based on a sequence of nucleotides in mRNA 20 different kinds of amino acids(aa) but only 4 different nucleotides. The code for each aa must be made up of at least three nucleotides= codon 41= 4 combinations 42= 16 combinations 43= 64 combinations More than one codon for certain amino acids as well as stop codons. For example GGG-GGA-GGC-GGU all encode a.a. Glycine BIOL 205 Dr. Chin-Sang's Lectures  The passage of genetic information must have four properties: 1. Diversity of structure: There must be information for the differences in cellular structures. 2. Ability to replicate: There must be some mechanism for replication so information can be passed from generation to generation. 3. Mutability: Information must be able to change. 4. Translation: A blueprint is not enough. You need the machinery to read and translate the information to build the structure. BIOL 205 Dr. Chin-Sang's Lectures Information transfer among biological molecules Gregor Mendel One of Mendel’s experiments  Some Genetic Terms You Must Know Wild-type: The “normal” or most common form– reference strain Mutants: variants of the wild-type form Genotype: Genetic composition Phenotype: A measurable character Allele: One of the different forms of a gene that can exist at a single locus Gene locus: The specific region on a chromosome where the gene is located Diploid: having two chromosome sets Haploid: having one chromosome set Homozygous: carrying a pair of identical alleles at one locus Eg. +/+ or m/m or A/A or a/a Heterozygous: carrying a pair of different alleles at one locus Eg. +/m or A/a Dominant: An allele that expresses its phenotypic effect even when heterozygous with a recessive allele; thus, if A is dominant over a, then A/A and A/a have the same phenotype.(gives rise to a dominant phenotype) Recessive: An allele whose phenotypic effect is not expressed in a heterozygote. If a is recessive, then you will only observe the phenotype when homozygous: a/a. (gives rises to a recessive phenotype) Single Nucleotide Polymorphisms  Which mutation will likely be a null allele? 5’ 3’ wild-type 5’ 3’ A * C->A in intron 1 5’ 3’ C->G in promoter B * TGG->TAG C 5’ * 3’ (Trp)->(Stop) in first exon D 5’ * 3’ TGG->TAG (Trp)->(Stop) in last exon E I have no clue  Not all mutations are created equal!  Genetic Variation Genetic variation is the genetic differences among individuals. Most people (except for identical twins*) do not share the same sequence of DNA. How does variation arise? 1. During Meiosis the random mixing of maternal and paternal chromosomes. The union of which egg and sperm is also random*. Variation arises by mutation: 1. Spontaneous (i.e. mistakes in replication) 2. Genetic variation can be produced in the laboratory by using high-energy radiation or chemicals to produce mutations. * Some caveats  Gene regulation is important! The genome in the nuclei of the 50 trillion cells is the roughly identical but we have so many different cell types. How? Not all genes are expressed (turned on ) in every cell Muscle cells turn on muscle specific genes Neurons turn on neuronal specific genes Eye cells must turn on the right genes to build and eye Genes and how they are regulated are important for all aspects of development, (not just making different types of cells) eg. Cell division, cell movements, pattern formation, organ and tissue formation. Messing up genes (mutations) and/or how they are regulated can lead many if not all human diseases. Genes control development. Forward genetics or classical genetics : Starts with a variant phenotype and tries to identify the genetic difference. Historically most genes were identified by mutation. If a fruit fly had white eyes (mutant) it meant you altered a gene involved in forming red eyes (wild-type).  Reverse genetics: starts with a gene of unknown function and looks at what happens to the organism/ cells when you alter that gene. Gene “X” What is the phenotype? What is it function?  Tools for genetic analysis Enzymes: Polymerases Nucleases eg. Restriction enzymes, Cas9 Ligases Techniques DNA sequencing PCR DNA Synthesis DNA transformation Genetically Modified Organisms (GMO) 64 Strands of nucleic acids hybridize to complementary sequences Strands of nucleic acids hybridize to complementary sequences  Genetics Today 1. Louise Benge: disease now called “arterial calcification due to deficiency of CD73,” or ACDC. 2) Whole Genome Sequencing to identify mutational risk. Genome sequences of parents and their children clarify the factors that contribute to new point mutations. 3) Flood tolerant rice— Genetics and genomics are playing a leading role in improving crop plants. 4) Recent evolution in humans: Adaptation to high altitude 67  Genetics Today From classical genetics to medical genomics Undiagnosed Diseases Program (UDP) A patient of Arterial Calcification due to Deficiency of CD73, (ACDC) an autosomal recessive condition. The complex genetics of color blindness What number do you see? A.74 B.21 C.Other The genes for the major form of colour blindness are on the X chromosome. This an example of sex-linked inheritance. X chromosome 8.3% of Men have red/green colour blindness 0.6% of Women have red/green colour blindness Blue opsin (on chr. 7) 0.01% of population have blue/yellow colour blindness Unequal crossing over can produce the chromosomes with disrupted genes.  X Unequal crossing over can lead to chromosomes missing an opsin gene  X Unequal crossing over between the red and green opsin genes can make hybrid opsins  Genetic model organisms Genetic Model Systems: Easy to grow and maintain Fast life cycle Can “cross” Cheap and abundant Model organisms are dispersed across the tree of life Drosophila melanogaster Caenorhabditis elegans Figure 1-13d 100um When thinking about genetics think about: Genes The gene products (RNA or Protein) The functions of those products are evolutionary conserved Though experiment