GENETICS-REVIEWER.pdf

GENETICS (REVIEWER) Old Ideas What is Genetics? 1. All life comes from other life. Living a branch of biology that deals with organisms are not spontaneously generated the heredity of an organism from non-living material. What...

GENETICS (REVIEWER) Old Ideas What is Genetics? 1. All life comes from other life. Living a branch of biology that deals with organisms are not spontaneously generated the heredity of an organism from non-living material. What is Inheritance? 2. Species concept: offspring arise only Every living thing has a set of when two members of the same species characteristics inherited from its mate. Monstrous hybrids don't exist. parent or parents. Genetics is the scientific study of 3. Organisms develop by expressing heredity. information carried in their hereditary material. Three Branches of Genetics opposed to "preformation": the idea that in each sperm (or egg) is a tiny, 1. Transmission Genetics (classical fully- formed human that merely genetics) grows in size. Transmission of genes from generation to generation and how 4. The environment can't alter the hereditary genes recombine. material in a directed fashion. There is no "inheritance of acquired characteristics". 2. Molecular Genetics Mutations are random events. Structure and functions of genes at the molecular level. 5. Male and female parents contribute equally to the offspring. 3. Population Genetics ancient Greek idea: male plants a Distribution of genes in populations. "seed" in the female "garden". (in mathematical term) History of Genetics and Genomics Why is Genetics important to Society? 1859 | Charles Darwin Agriculture (genetically engineered Publication of "The Origins of plants, wheat resistant to rust) Species", a treatise that formally outlined the theory of evolution via Livestock (different breeds, leaner natural selection beef, polled vs. horned cattle) 1865 | Gregor Mendel Medicine (to discover the The concept of particulate (gene) cancer-causing gene, diagnose a inheritance was established. The disease, gene therapy, genetic laws of segregation and independent screening, etc.) assortment were demonstrated. The publication is entitled "Experiments in Plant Hybridization" and outlines the famous "pea experiments.'  1902 | Walter Sutton Theodor Boveri 1866 | Ernst Haeckel Within a specific species, each Proposes the idea that the chromosome is described as having hereditary material resides in the unique physical characteristics. It is nucleus. shown that chromosomes occur in pairs, one parent contributes each 1871 | Friedrich Miescher member of the pair, and the pairs The term nuclein is used for the separate during meiosis. Sutton material found inside the nucleus of suggests chromosomes are a a cell. Further experiments (1874) physical manifestation on which the revealed nuclein consisted of a unit of heredity resides. This came to nucleic acid and protein. be known as the chromosomal theory of inheritance. 1879 | Walter Fleming Described chromosome behavior 1902 | Archibald Garrod during animal cell division. He stains The first human disease is described chromosomes to observe them that exhibits Mendelian inheritance. clearly and describes the whole The disease is alkaptonuria. Later process of mitosis in 1882 (1909) Garrod is the first to discuss the biochemical genetics of man. 1899 | William Bateson The use of hybridization between 1902 | William Bateson two individuals is described as a tool The terms genetics, homozygote, of the scientific analysis of heredity. heterozygote, epistasis, F1, F2, and This again was discovered to be an allelomorph (shortened later to important tenet of Mendel's work. allele) were first used. 1900 | Carl Correns Hugo de Vries Erich 1903 | Wilhelm Johannsen von Tschermak The important concepts of Mendel's work is rediscovered phenotype, genotype, and selection independently, de Vries and Correns were elucidated. The terms were were experiments similar to those of actually coined later (1909). Mendel and arrived at similar results. Once they read Mendel's paper, they 1910 | Thomas Hunt Morgan recognized its pre-eminence and The first demonstration of sex made the world aware of it. linkage in Drosophila is published. This suggested genes reside on 1900 | Hugo de Vries chromosomes. The era of fruit fly as The term mutation is used to a model organism begins. describe the apparently spontaneous appearance of new 1928 | Frederick Griffith traits in evening primrose Transformation of Pneumococci is obtained. This is the critical experiment that leads to the  eventual discovery that DNA was the sequences in the DNA molecule and genetic material. the production of proteins. 1944 | Oswald T. Avery, Maclyn McCarty, 1961 | Marshall Nirenberg Colin M. MacLeod The concept that each amino acid Extending the experiments of Griffith corresponds to a triplet code was (1929), it is first shown that DNA is developed. The first correspondence the genetic material. This fact is was found between the triplet AAA often lost, and this discovery is often and the amino acid phenylalanine. afforded to Hershey and Chase (1953). 1997 | E. coli genome project 1950 | Erwin Chargaff E. coli (4.7 Mbp) is sequenced and Adenine thymine and guanine shown to contain 4,500 genes. cytosine. It is demonstrated that within all DNA molecules, the 2001 | International Human Genome number of adenines equals the Sequencing Consortium Celera Corp number of thymine, and the number The human genome sequence of guanine equals the number of (2900 Mbp) is published. It is cytosine. estimated that the genome contains between 35,000 and 40,000 genes. 1952 | Alfred Hershey, Martha Chase Later (2002) estimates place the The classic "blender experiment" is number at 30,000 genes. reported that shows that phage DNA enters (along with a little protein) 2002 | Mosquito Sequencing Consortium and leads the eventual rupture of the The malaria-parasite-carrying cell. This is often, and mistakenly, mosquito genome sequence (278 considered the definitive experiment Mbp) is published. It is shown to proving that DNA is the genetic contain 13,600 genes, similar to the material. number found in Drosophila 1953 | James Watson, Francis Crick 2003 | British Columbia Cancer Agency A structural model of DNA is The SARS-associated coronavirus presented that states it consists of genome sequence (30 Kbp) is two anti-parallel chains held together released. The genome contains 16 by hydrogen bonds. The model open- reading frames. The suggests a model of DNA sequence is released less than five replication. months after the disease began spreading world- wide. 1957 | Francis Crick The central dogma of molecular History of Genetics biology is proposed. This is a first People have known about elucidation of the link between the inheritance for a long time  ○ children resemble their 1926: Hermann J. Muller shows that X-rays parents induce mutations. ○ domestication of animals and plants, selective breeding for 1944: Oswald Avery, Colin MacLeod and good characteristics Maclyn McCarty show that DNA can ○ Sumerian horse breeding transform bacteria, demonstrating that DNA records is the hereditary material. ○ Egyptian data palm breeding 1953: James Watson and Francis Crick Mid 1800's Discoveries determine the structure of the DNA molecule, which leads directly to knowledge 1866: Gregor Johann Mendel of how it replicates founder of the modern science of genetics 1966: Marshall Nirenberg solves the genetic publishes Experiments in Plant code, showing that 3 DNA bases code for Hybridization, which lays out the one amino acid. basic theory of genetics widely ignored until 1900. 1972: Stanley Cohen and Herbert Boyer combine DNA from two different species in 1871: Friedrich Miescher isolates "nucleic vitro, then transform it into bacterial cells: acid" from pus cells first DNA cloning. 1900: rediscovery of Mendel's work by 2001: Sequence of the entire human Robert Correns, Hugo de Vries, and Erich genome is announced. von Tschermak. Genetics: Terms and Definitions 1902: Archibald Garrod discovers that alkaptonuria, a human disease, has a Trait genetic basis. Characteristic, usually a physical characteristic of a living organism, 1904: Gregory Bateson discovers linkage such as the height of a plant or the between genes. Also coins the word hair color of a mammal. "genetics". Gene 1910: Thomas Hunt Morgan proves that A piece of DNA that carries the genes are located on the chromosomes information needed to make a (using Drosophila). specific protein. Units of heredity 1918: R. A. Fisher begins the study of Traits are produced by an interaction quantitative genetics by partitioning between genes and their phenotypic variance into a genetic and an environment environmental component. Gregor Mendel Levels of Genetics and Genomics Austrian Monk Born 1822 in Czech Republic Molecular Worked at monastery and taught Cellular high school Tissues Tended the monastery garden Organs Grew peas and became interested in Individuals the traits that were expressed in Families different generations of peas Population Evolution of Species What Is Genetics? It is the study of inherited traits and True breeding their variation. If allowed to self-pollinate they would Certain difficult-to-define human produce offspring identical to characteristics might appear to be themselves inherited if they affect several family He was also able to cross breed members but may reflect shared peas for different traits genetic and environmental influences. Genetic Information Genome the complete set of genetic instruction. Human genome was completed in 2003 which started in 1990 Genomics field that analyzes and compares genomes of different species Genes and Dominance THE HUMAN GENOME PROJECT (HGP) Mendel studied seven different pea 1990 - 2003 plant traits Each trait he studied had a "The human genome underlies the contrasting form fundamental unity of all members of the The offspring of crosses between human family, as well as the recognition of parents with different traits are called their Inherent dignity and diversity. In a Hybrids symbolic sense, it is the heritage of When Mendel crossed plants with humanity.” different traits he expected them to Universal Declaration on the Human blend, but that's not what happened Genome and Human Rights at all.  All of the offspring had the character Mendel's 2nd conclusion of only one of the parents 2. The Principle of Dominance Pea Plants Traits Some alleles are dominant and some are recessive Flower Color Dominant: Purple Dominant Recessive: White Covers up the recessive form Ex.) T = tall Flower Position Dominant: Axial Recessive Recessive: Terminal Gets covered up in the presence of a dominant allele Seed Color Ex.) t = short Dominant: Yellow Recessive: Green Hints for working with genetic traits.. traits are assigned letters Seed Shape the recessive trait usually provides Dominant: Round the letter designate Ex// round vs. Recessive: Wrinkled wrinkled = W round w= wrinkled (be sure to keep your writing neat Pod Shape enough so that you can read the Dominant: Inflated letters) Recessive: Constricted Capital letters refer to dominant traits while lower case letters refer to Pod Color recessive traits Dominant: Green Letters usually appear in pairs Ex// Recessive: Yellow Round WW vs Wrinkled = ww remember the genotype will tell you Stem Length the phenotype. Dominant: Green Recessive: Yellow Segregation Mendel wanted to answer another Mendel drew two conclusions question Q: Had the recessive alleles 1. Inheritance is determined by factors disappeared? Or where they still that are passed from generation to present in the F, plants? generation - today we call these To answer this he allowed the F, factors genes plants to produce an F, generation by self pollination Alleles Different forms of a gene The F₁ Cross The recessive traits reappeared!  Roughly 1/4 of the F₂ plants showed Punnett Square a recessive trait Diagram used to determine genetic crosses Explanation of the F₁ Cross Named after Reginald C. Punnett The reappearance indicated that at A way of visualizing various crosses some point the allele for shortness Aids in problem solving had been separated from the allele The square represents all possible for tallness random fertilization events. Mendel suggested that the alleles for tallness and shortness in the F1 Homozygous plants were segregated from each Organisms that have 2 identicle other during the formation of sex alleles for a trait Ex.) TT, tt cells or gametes When each F1 plant flowers, the two Heterozygous alleles segregate from each other so Have two different alleles for a trait that each gamete carries only a Ex.) Tt single copy of each gene. Therefore, each F1 plant produces two types of Phenotype gametes - those with the allele for Physical characteristics - (words) tallness and those with the allele for Ex.) tall shortness Genotype Probability and Punnett Squares Genetic make-up - (letters) Ex.) Tt, TT, tt Mendel kept obtaining similar results, he soon realized that the Methods in Studying Genetics principals of probability could be used to explain the results of genetic Highlights crosses Karyotyping Probability Chromosomal banding The likelihood that a particular event Polymerase chain reaction will occur Gel electrophoresis The way in which alleles segregate Whole genome sequencing is random like a coin flip Gene Editing Gene cloning Punnett Square Vocab DNA Profiling If you do not know the following vocabulary words you will fait The Human Karyotype miserably Karyotype A karyotype is the complete set of chromosomes in a specie. It describes the number of  chromosomes, and what they look Useful for determining the presence like under a light microscope. of dicentric and pseudodicentric It is a photographic representation of chromosomes, and for studying a stained metaphase spread in marker chromosomes and which the chromosomes are polymorphic variants. arranged in order of decreasing With CBG banding (C-bands, by length. barium hydroxide, using Giemsa), the DNA is selectively depurinated Specimens that contain and denatured by barium hydroxide, spontaneously proliferating cells and the fragments are washed away include bone marrow, lymph nodes, by incubation in a warm salt solution. solid tumors, and chorionic villi Peripheral blood lymphocytes, tissue selectively stain the constitutive biopsies, and amniotic fluid samples heterochromatin around the are routinely cultured to obtain centromeres, the areas of inherited dividing cells; lymphocytes usually polymorphisms present on require the addition of a mitotic chromosomes 1, 9, and 16, and the stimulant. distal long arm of the Y The choice of specimen for chromosome. chromosome analysis depends on clinical indications and whether the 2. T-Banding (Telomere Banding) - diagnosis is prenatal or postnatal A harsher treatment of the chromosomes diminishes staining CHROMOSOME STAINING AND except at the heat-resistant BANDING telomeres. A chromosome band is a part of chromosome that is clearly 3. NOR Staining (Silver Staining for distinguishable from its adjacent Nucleolar Organizer Regions) - Nucleolar segments comprised of alternating organizer regions (NORs) located on the light and dark stripes. satellite stalks of the acrocentric chromosomes. - Silver nitrate is used to Banding and staining techniques can stain the regions that contain genes for be divided into two broad categories: ribosomal RNA those that produce specific alternating bands along the length of Cytogenetics each entire chromosome and those Cytogenetics focuses on the that stain only a specific region of microscopic examination of genetic some or all chromosomes components of the cell, including chromosomes, genes, and gene Techniques that Stain Selective products. Chromosome Regions Biochemical methods are applied to the main chemical compounds of 1. C-Banding (Constitutive genetics-notably DNA, RNA, and Heterochromatin Banding) protein.  then utilized as template sequence Biochemical techniques are used to for following PCR reaction determine the activities of genes Application: detect RNA expression within cells and to analyze substrates and products of gene- Nested Polymerase Chain Reaction controlled reactions. Developed to increase sensitivity POLYMERASE CHAIN REACTION (PCR) and specificity of PCR WHAT IS PCR? Two primers set are used sequentially. The 1st set is applied to called "molecular photocopying," ampimy a target sequence then the used to "amplify" - copy small acquired amplicons is utilized as the segments of DNA. target sequence for a 2nd PCR is a novel molecular technique reaction by internal primers involving in vitro enzymatic replication of defined DNA Major concern for this method is sequences contamination, which could be used to diagnose diseases, identify avoided by physically separating the bacteria and viruses, match first- and second-round amplification criminals to crime scenes, and mixtures with a layer of wax or oil. biotechnology. Application: non-specific binding in PCR Protocol products due to the amplification of unexpected primer binding sites 1. Denaturation of dsDNA template - thermal denaturation of dsDNA at 94°C Digital Polymerase Chain Reaction 2. Annealing of two oligonucleotide primers accomplished by capturing or temp. is decreased to 50-60°C which allows isolating each individual nucleic acid primers to attach to complementary molecule present in a sample within sequences many chambers, zones, or regions that can localize and concentrate the 3. Polymerase extension of DNA molecules amplification product to detectable temp. is raised at 72-74°C just below the levels optimum of Taq polymerase After PCR quantification, a count of Reverse- Transcriptase Polymerase the areas containing PCR product is Chain Reaction a direct measure of the absolute quantity of nucleic acid in the developed to amplify RNA targets sample. RNA molecule via reverse no rely on reference standards transcriptase verted to cDNA molecule enzyme is convert and  Applications evaluating the quantity Buffer system: Conduct electricity by DNA and RNA molecules exists in a running buffer sample Gel Electrophoresis GEL ELECTROPHORESIS A type of electrophoresis in which supporting medium sa gel Electrophoresis Separation brought about through molecular sieving technique, based A method of separating electrically on molecular size of the substances charged substances in mixture Gel material acts as a "molecular a sample of the mixture is placed on sieve” a supporting medium, to which an The technique is widely used for electrical field is applied separating proteins and nucleic acids General Principle Each charged substance migrates toward cathode the anode at a speed d that or depends on its net charge, size and shape. When an electrical field is applied to a solution, solute molecules with a net positive charge migrate toward the cathode, and molecules with a net negative charge move toward the anode Electrostatic attraction causes WHOLE GENOME SEQUENCING biomolecules to migrate towards the electrodes of opposite charge WHAT IS WHOLE GENOME SEQUENCING Father of Electrophoresis Genome sequencing involves finding Arne Tiselius did pioneer work on out the whole sequence of a moving boundary electrophoresis person's DNA. (1930) and later developed a zone laboratory procedure that method for the purification of determines the order of bases in the biomolecules genome of an organism in one process. Electrophoresis: 3 PARTS WHOLE GENOME SEQUENCING: Voltage: power supply DISCOVERY Supporting medium: Matrix in which the biomolecules naseparation takes place Sanger and his colleagues invented chain termination sequencing I 1970  differences. The number of Fragments of 100-1000 base pair differences can tell the scientists In 1979 SHOTGUN SEQUENCING how closely related the bacteria are, TECHNIQUE was developed and how likely it is that they are part Large size of fragments of the same outbreak. Overlapping of discovered fragments to detect whole genome sequences. WHOLE GENOME SEQUENCING: ADVANTAGES How does whole genome sequencing work Creating personalized plans to treat disease may be possible based not Scientists conduct whole genome only on the mutant genes causing a sequencing by following these four main disease, but also other genes in the steps: patient's genome. DNA shearing: Scientists begin by Genotyping cancer cells and using molecular scissors to cut the understanding what genes are mis DNA, which is composed of millions regulated allows physicians to select of bases: A's, C's, T's and G's, into the best chemotherapy and pieces that are small enough for the potentially expose the patient to less sequencing machine to read. toxic treatment since the therapy is tailored. DNA bar-coding: Scientists add small pieces of DNA tags, or bar Previously unknown genes may be codes, to identify which piece of identified as contributing to a sheared DNA belongs to which disease state. Traditional genetic bacteria. This is similar to how a bar testing looks only at the common code identifies a product at a "troublemaker" genes. grocery store. Lifestyle or environmental changes Whole genome sequencing: The that can mediate the effects of bar-coded DNA from multiple genetic predisposition may be bacteria are combined and put in the identified and then moderated. whole genome sequencer. The sequencer identifies the A's, C's, T's, WHOLE GENOME SEQUENCING: and G's, or bases, that make up DISADVANTAGES each bacterial sequence. The sequencer uses the bar code to The role of most of the genes in the keep track of which bases belong to human genome is still unknown or which bacteria. incompletely understood. Data analysis: Scientists use Most physicians are not trained in computer analysis tools to compare how to interpret genomic data. bacterial sequences and identify  An individual's genome may contain genetic modification, but it also has information that they DON'T want to the benefit of allowing producen to know. improve crops without adding genes from other organisms- The volume of information contained in a genome sequence is vast. With gene editing, researchers have made seedless tomatoes, gluten- GENE CLONING free wheat and mushroom that do not turn to brown. Insertion of a fragment of DNA carrying a gene into a cloning vector Companies working on and subsequent propagation of next-generation antibiotics have recombinant DNA molecules into developed otherwise harmless many copies is known as gene viruses that find and attack specific cloning strain of bacteria that cause Involves using bacteria to make dangerous infections. multiple copies of a gene Foreign DNA is inserted into a Meanwhile, researchers are using plasmid, and the recombinant gene editing to make pig orgam safe plasmid is inserted into a bacterial to tramplant into humans. cell Reproduction in the bacterial cell Gene editing has transformed results in cloning of the plasmid fundamental research too, allowing including the foreign DNA scientists to understand precisely This result in the production of how specific genes operate. multiple copies of a single gene The Crispr-Cas9. Gene Editing It uses a guide molecule (the Crispr bit) to Scientists liben it to the find and find a specific region in an organism's replace feature used to correct genetic code misspellings in documents written on a mutated gene, which is then cut by a computer. Instead of fixing words, an enzyme (Cas9) gene editing rewrites DNA, the biological code that makes up the Will it lead to designer babies? instruction manuals of living organisms. The overwhelming effort in medicine is aimed at mending faulty genes in The agricultural industry has leapt children and adults. on gerne editing for a host of A handful of studies have shown it reasons should be possible to fix dangerous mutations in embryos too The procedure is faster, cheaper and more preche than conventional  Traits like these can involve HEALTH CARE thousands of genes, most of them unknown. Diseases are viewed as the So, for the time being, designer consequence of complex babies are a distant prospect. interactions among genes and environmental factors. DNA PROFILING Some people are more susceptible What is DNA Profiling to contracting certain infections than DNA profiling is simply the others due to inherited differences in collection, processing and analysis immunity. of VNTRS - unique sequences on the loci (area on a chromosome). Genes affect how people respond to VNTR stands for variable number particular drugs. tandem repeats - meaning the - Pharmacogenomics is a field tandem repeats, or pairs of that identifies individual drug nucleotides, vary in number. reactions based on genetics. a technique that can be used to determine paternity or help solve crimes where the suspect may have left a sample of body tissue at the crime scene. Identification of victims of natural disasters or terrorist attacks Matching the DNA of suspects to samples left at the crime scene Helping adopted individuals locate blood relatives HISTORY AND ANCESTRY DNA analysis can clarify details of history Revealing the offspring of Thomas Jefferson and Sally Hemmings Provide views into past epidemics by detecting genes of the pathogens Revealed the presence of malaria in the analysis of DNA of king Tutankhamun's mummy