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CS 159: GENETICS LECTURERS: 1.Prof. Richard Akromah [BSc Agric.(Kumasi), MSc (Birmingham), PhD (Reading)] 2.Mr. Alexander Wireko Kena [BSc Agric. (Kumasi), MSc (Ibadan)] What is Genetics? The term GENETICS comes from the word “GENE”. Genes are the focus of the subject. Genes are the biological elements or factors that determine the inherent properties or characteristics of organisms (HEREDITY), which are transmitted from parents to offspring from generation to generation. Technically, a gene is a section of a threadlike double helical molecule called deoxyribonucleic acid (DNA). Simply, genetics is the study of genes. Some also define genetics as the study of heredity. However, heredity studies were of interest to humans long before genetics as a scientific discipline existed as we know it today. The study of genetics began in the early part of the 20th Century after advances were made in CYTOLOGY and the discovery of the LAWS OF HEREDITY in 1860’s. Why study Genetics? Genetics is an indispensable discipline that occupies a pivotal position in the life sciences. Genetic knowledge gives insight into the mysteries of biology. It helps us to explain mysteries such as Why likes beget likes and dislikes (resemblance and variation within a species) The origin of the individual Why certain diseases persist in a family • To the agriculturist, a good knowledge of genetics principles is a prerequisite for conducting crop and animal improvements for higher productivity through breeding. What to Expect…..? In this course, you will basically learn about GENES The nature of genes (where they are found, their structure; both physical and chemical structure) How genes were discovered How genes perform their biological roles The science of genetics is studied at the molecular (sub-cellular), cellular, organismal, family and population levels of life. Cell Theory: Cells are the basic units of organization, structure and function in living organisms. All organisms are made up of at least one cell. Cells are derived from pre-existing cells (i.e. all cells trace back to one original cell). Life progresses by enlargement and division of cells. Cell Structure and Organization There are two basic types of cells: 1. Cells without a nucleus = Prokaryotes [Pro = before evolution of karyotes] (e.g., bacteria, blue-green algae) Generally very small, unicellular, the earliest and still most abundant life forms 2. Cells with a nucleus = Eukaryotes Some are unicellular (protists – amoeba), some multicellular forms (fungi, plants, animals) Prokaryote versus Eukaryote Similarities: Both are enclosed within a lipid bilayer cell membrane – plasma membrane Differences: Eukaryotes bound organelles contain membrane Prokayotic cell – DNA is concentrated into a nucleoid, but no membrane system separates this region from the rest of the cell Eukayotic cell – has a true nucleus bound by a membranous nuclear envelope Viruses – no typical structure. E.g. a Phage particle consists of a protein coat surrounding a core of genetic material which may be DNA or RNA. They are not really living since they cannot exist alone, but require cells to infect How do you see cells? – microscopes (light, electron) Eukaryotic Cells Living material is Protoplasm Protoplasm = Nucleus + Cytoplasm Cytoplasm The part of a cell enclosed by the plasma membrane but excluding the nucleus Cytoplasm contains organelles - any of the structures that occur within a cell e.g., mitochondria, lysosomes (ref organs) Nucleus The central structure (master control center ) of eukaryotic cells. Concerned with replication or reproduction Structure: Two unit membranes with a fluid-filled space Nuclear pores present Outer membrane may endoplasmic reticulum. be continuous with Chromatin: it is a complex of long DNA strands wrapped around proteins. When condensed = chromosomes Function: contains instructions that control cell metabolism and heredity Nucleolus:non-membraneous matrix (ribonucleic acid) and protein of RNA Function: instructions in DNA are copied here (ribosomal RNA synthesis) works with ribosomes in the synthesis of protein Mitochondrion (plural: mitochondria) Structure: composed of modified double unit membrane (protein, lipid) Function: centres for respiratory catabolism, i.e. the release of chemical energy from food Physiology Glucose + Oxygen ------> Carbon Dioxide + Water + Energy (ATP) Chloroplasts = Found only in plant cells. Structure: composed of a double layer of modified membrane (protein, chlorophyll, lipid) - inner membrane invaginates to form layers called "grana" (sing., granum) where chlorophyll is concentrated Function: Centre for photosynthetic anabolism Carbon Dioxide + Water ---------------> Glucose + Oxygen radiant energy Ribosomes: Structure - non-membraneous, spherical bodies composed of RNA and protein enzymes Function: Sites for synthesis of protein from RNA template Lysosomes [Greek lysis dissolution + soma body]. Only in animal cells. Structure: membrane bound bag containing hydrolytic enzymes - hydrolytic enzyme = (water split biological catalyst) i.e. using water to split chemical bonds Function: break large molecules into small molecules by inserting a molecule of water into the chemical bond Cytomembrane (endomembrane) system This is a series of membranous vesicles involved in coordinating protein production and secretion. Their structure and organization depends very much on the cell and its mission Plasma membrane Structure: the thin semi-permeable layer of protein and fat that surrounds the cell, but is inside the cell wall in plants Function: acts as a boundary layer to contain the protoplasm - interlocking surfaces bind cells together - selectively permeable to select chemicals that pass in and out of cells Cell Wall Structure: - a thick, rigid membrane of cellulose that surrounds a plant cell (a non-living secretion of the cell membrane) - contains pits (openings) that make it totally permeable Function: - provides protection from physical injury - together with vacuole, provides skeletal support Endoplasmic reticulum (ER) Structure: - sheets of unit membrane with ribosomes on the outside - forms a tubular network throughout the cell Function: - transports chemicals between cells and within cells - provides a large surface area for the organization of chemical reactions and synthesis Golgi complex Structure: stacks of flattened sacs of unit membrane (cisternae) - vesicles pinch off the edges Function: - modifies chemicals to make them functional - secretes chemicals in tiny vesicles - stores chemicals - may produce endoplasmic reticulum Vacuole Structure: - a single layer of unit membrane enclosing fluid in a sack Function: -produces turgor pressure against cell wall for support, stores water and various chemicals - may store insoluble wastes Cytoskeleton: A network of fiber-like structures in the cytoplasm that provide form for the cell and that may have other functions also The contents of a cell are highly organized, rather than flopping around randomly. Cell structure is maintained by a cytoskeleton of microtubules and microfilaments. Microtubules are composed of primarily a single protein called tubulin that stacks up into long filaments. They act like tiny molecular “strings”, forming the basic skeleton of the cell, maintaining the cell shape and providing a "highway system" along which cell constituents are transported. (This is especially important in nerve axons, which may be several feet in length.). Cilia and flagella (both plural) These structures are involved in many forms of motility, either of the cell with respect to its environment (e.g. sperm with flagella and paramecia with cilia) or to move substances across cell surfaces, e.g. nasal cilia or pharyngeal cilia. They are all based on microtubules that run the length of the cilium or flagellum. At the base of these microtubules is the centrosome which is also involved in organizing microtubules during cell division. In most species the centrosome is made up of a pair of centrioles. Seed plants and a few other organisms do not have centrioles. Structures specific to plant cells, called “basal bodies” seem to take the place of centrioles. Organization of Chromosomes Chromo = Colour Some = Body Chromosome = A structure composed of DNA and proteins that bears the genetic information of a cell It is favourable to observe chromosomes during metaphase when both chromatids are still joined Chromosomes vary in structure Karyotype [Greek karyon, kernel] is the depiction of the chromosomes of an organism, normally from a mitotic cell in metaphase. Chromosome size is one criteria used to construct karyotypes. In addition, the position of the centromere that determines relative arm lengths and presence or absence of satellites are important for chromosome description A typical chromosome has: Centromere [Latin centrum center + Greek meros part.] The position on a chromosome at which the spindle fibers attach in cell division. It divides the chromosome into two arms The centromere is chromosome to divide the last part of the There is also a secondary constriction beyond which is the knob or satellite. It also marks the position of the nucleolus. e Classification of chromosome according to centromere position Classification of chromosome according to centromere position Metacentric - about midway between arms giving similar but not usually identical lengths – V shape at anaphase. [Meta = middle] Submetacentric - about midway between the centre and the end of one arm – L shape at anaphase Acrocentric - Very near the tip of one arm such that the other is very short – ‘I’ shaped. [Greek akron extremity + centric centre] Telocentric - Terminal so there is only one arm (telos = end) Acentric - A chromosome or, more commonly, a chromosome fragment that lacks a centromere Chromatin Structure/DNA organization - Olins and Olins used electron microscopy to observe “beads on a string discussed under DNA structure Condensation (super-coiling) of DNA – discussed under DNA structure Chromosome theory of inheritance Hereditary characters are carried and passed on to offspring in discrete units in chromosomes (Correlation between Mendelian inheritance and chromosome behaviour) Cytogenetics = The study of chromosome number, structure, function and behaviour in relation to gene inheritance, organization and expression The Cell Cycle: The cell cycle is a series of stages through which the cell passes between divisions and is composed of three stages - Interphase, Nuclear division (Karyokinesis) and Cytokinesis A. Interphase is the period between divisions when nothing seems to be happening (gap phase or resting nucleus). The chromosomes are so decondensed (strung out) that they are invisible. The chromatin (DNA and protein) that makes up the chromosomes is still there but it’s so dispersed that only a few dark blotches of chromatin (called nucleoli) can be seen. It is abbreviated as G phase and dominates the cell cycle. The Cell Cycle S - Each chromosome is replicated to form two sister chromatids. The centrosome is also duplicated. G1 – GROWTH (cell gets food uses E, grows in size) major period of cell growth New organelles are synthesized G2 - cell undergoes a period of rapid growth to prepare for mitosis. Microscopes were not very informative about G phase but its chemistry enabled division into: G1 (or Gap 1) – is “early interphase” and occurs after cytokinensis, the last cell division, but before start of DNA synthesis. Cell recovers from previous cell division and grows larger. Cells that do not divide never move to S phase so they never replicate their DNA e.g., most nerve cells (neurons). Cells in G1 have only one centrosome S phase (or Synthesis phase) is the time when DNA is synthesized. Each single chromatid (inherited from the previous nuclear division) is duplicated to give identical sister chromatids. The chromatid now contains one parental and one new strand (= semiconservative replication - one old strand is completely conserved and the other strand is completely new). G2 (or Gap 2) occurs after S phase but before the next M phase. The cell prepares for mitosis and cytokinensis. A cell in G2 has twice as much DNA as it had in G1 because of synthesis in the S phase. During G2 the centrosome is duplicated so by late G2 the cell has two centrosomes. This tells us we are nearing M phase. All cells must have 2 centrosomes to guide the chromosomes during the M phase that follows. Interphase = The part of the nuclear cycle following the end of one division to the beginning of the next. Interphase can be divided into three parts: G1, in which the DNA has yet to replicate; S, the period in which DNA replication occurs; and G2, the period between S and the beginning of mitosis or meiosis B. Nuclear Division is when the genetic material is dividing and chromosomes can be seen. There are two types – mitosis and meiosis. It is called the M phase. During this phase one mother nucleus becomes two daughter nuclei. Mitosis is the nuclear division associated with the proliferation of somatic cells. The main function of mitosis is to increase the number of identical nuclei. When followed by cytokinesis, as it usually is, mitosis increases cell numbers. Each division produces two identical daughter cells During mitosis, each chromosome in the duplicate longitudinally, into chromatids, and double structure splits to become two chromosomes, each going to a different nucleus nucleus then the daughter daughter Each chromosome consist of a single double helix DNA molecule. During S phase DNA unwinds and duplicates into 2 identical copies, thus the cell has twice as much DNA in this phase, forming the sister chromatids Mitosis is divided into four distinct stages: Prophase, metaphase, anaphase and telophase Prophase is the initial phase of mitosis and meiosis. The chromosomes condense and become visible. The nuclear membrane disappears and spindle fibres start extending from the poles of the cell. Prophase ends when the chromosomes align to form metaphase Metaphase is the phase of mitosis or meiosis in which chromosomes are maximally condensed and are aligned in a plane between the poles of the spindle (metaphase plate). Metaphase marks the end of prophase. It is followed by anaphase Anaphase [Greek ana back + phase.] The phase of nuclear division in which newly formed chromosomes are pulled along the microtubules of the spindle to the opposite poles. In mitosis, former sister chromatids, chromosomes, move to opposite poles now Telophase is the final phase of nuclear division. The chromosomes uncoil and become very extended, a nuclear membrane forms around them, and the new nucleus enters interphase C. Cytokinensis [kinesis = motion] is “proper” cell division. The cytoplasm of the mother cell divides into two daughter cells (one mother cell becomes two daughter cells). A cell in cytokinensis has two nuclei formed by nuclear division during M phase. Most cells (but not all) divide their cytoplasm pretty evenly. Animal cells do not have a cell wall so they divide by a method called furrowing. During furrowing the cell membrane puckers inward along the cells “equator” as if an invisible thread were tightening between the two parts. E Eventually the furrowing pinches the cell into two. The “thread” is actually fibres of proteins, microtubules, attached to the inside of the cell membrane. Microtubules constict like a muscle. Plant cells have rigid cell walls so they cannot divide by furrowing. Instead, vesicles from the Golgi apparatus appear along the “equator” roughly midway between the daughter nuclei and with the help of microtubules, the vesicles fuse to form new cell membrane and add to the formation of a cell plate. The cell plate grows until it becomes a proper cell wall. Mitosis ensures that both nuclei have exactly equal genetic information, but cytokinensis distributes the organelles (mitochondria, ribosomes, etc) and cytoplasm randomly. The cell will be viable as long as enough organelles are present Mitotic Division – phase 1 Time–lapse films of living, dividing cells mitosis is broken down into five stages: prophase, prometaphase, metaphase, anaphase, telophase. PROPHASE: -Chromatin shows up under the microscope as well defined chr’s -Chromosomes seen as an X shape 2 sister chromatids connected by a centromere -Mitotic spindle begins to form and Elongate from the centrosome region Chromatin is the complex of DNA and protein that makes up chromosomes PROMETAPHASE: -Nuclear membrane dissolves -Spindle microtubules enter nucleus and some attach to the centromeric region of the chromosome -those microtubules that do attach at the kinetochore and are called kinetochore microtubules -the other microtubules are called non-kinetochore and polar Mitotic Division – Phase 2 Overlapping with the latter stages of mitosis, cytokinesis completes the mitotic phase. METAPHASE: -kinetochore microtubules push from opposite poles equally so that the chromosomes are aligned in the middle of the cell -this center area where the alignment occurs is called the metaphase plate ANAPHASE: -paired sister chromatids separate as kinetochore microtubules shorten rapidly -polar microtubules lengthen as kinetochore microtubules shorten, pushing poles of cell further apart TELOPHASE: -separated sister chromatids group at opposite ends of the cell, near the centrosome region, having been pulled there by receding microtubules -new nuclear envelope reforms around each group of separated chromosomes -Mitosis is over! Mitotic Spindle • Segregates chromosomes during cell division (either mitosis or meiosis) to the daughter cells • Consists of a bundle of microtubules joined at the ends but spread out in the middle Image is of the mitotic spindle at metaphase. The kinetochores of a chromosome′s two sister chromatids face in opposite directions. Here, each kinetochore is actually attached to a cluster of kinetochore microtubules extending from the nearest centrosome. Nonkinetochore microtubules overlap at the metaphase plate (TEMs). Kinetochore •Each of the two sister chromatids of a chromosome has a kinetochore = is a proteins structure associated with specific sections of chromosomal DNA at the centromere. •Kinetochore links the chromosome to microtubule polymers from the mitotic spindle during mitosis and meiosis • Contains two regions: an inner kinetochore, which is tightly associated with the centromere DNA; and an outer kinetochore, which interacts with microtubules However, experimental evidence supports the hypothesis that the primary mechanism of movement involves motor proteins on the kinetochores that “walk” a chromosome along the attached microtubules toward the nearest pole. Meanwhile, the microtubules shorten by depolymerizing at their kinetochore ends Mitosis is often called "copy division" because the genetic material is copied. Cytokinesis – animal vs plant 2. Cytokinesis in plant cells, which have cell walls, is different. There is no cleavage furrow. Instead, during telophase, vesicles derived from the Golgi apparatus move along microtubules to the middle of the cell, where they come together, producing a cell plate (Figure12.9b ). Cell wall materials carried in the vesicles collect in the cell plate as it grows. The cell plate enlarges until its surrounding membrane fuses with the plasma membrane along the perimeter of the cell. Two daughter cells result, each with its own plasma membrane. And a new cell wall arising from the contents of the cell plate has formed between the daughter cells. 1. In animal cells, cytokinesis occurs as cleavage. The first sign of cleavage is the appearance of a cleavage furrow, a shallow groove in the cell surface near the old metaphase plate (Figure 12.9a ). On the cytoplasmic side of the furrow is a contractile ring of actin microfilaments associated with molecules of the protein myosin. (Actin and myosin are the same proteins that are responsible for muscle contraction as well as many other kinds of cell movement.) The actin microfilaments interact with the myosin molecules, causing the ring to contract. The cleavage furrow deepens until the parent cell is pinched in two, producing two completely separated cells, each with its own nucleus and share of cytosol and organelles. DNA must Replicate before division can take palce A model for DNA replication: the basic concept. A short segment of DNA has been untwisted into a structure that resembles a ladder. The rails of the ladder are the sugar–phosphate backbones of the two DNA strands; the rungs are the pairs of nitrogenous bases. Simple shapes symbolize the four kinds of bases. Dark blue represents DNA strands present in the parent molecule; light blue represents free nucleotides and newly synthesized DNA. Replication begins at the DNA start site: the origin of replication The reaction is catalyzed by an enzyme: DNA polymerase - An enzyme that catalyzes the elongation of new DNA at a replication fork by the addition of nucleotides to the existing chain. Meiosis [Greek meiosis diminution] Upon fertilization two nuclei fuse, so that the number of chromosomes does necessarily double. An exponential growth of the number of chromosomes from generation to generation would thus have to be expected. This is not the case, because the chromosomes are reduced to half their normal number in germ cell production. Meiosis is a two stage type of cell division in sexually reproducing organisms that results in gametes with half the chromosome number of the original cell. It consists of two successive mitosis-like divisions: in the first division the number of chromosomes is reduced to their half (reduction division), the second is a normal mitosis (equational division) Meiosis I - The first of two divisions in meiosis, often abbreviated MI. In Prophase 1 the nuclear envelope disintegrates and chromosomes become visible as in mitosis (1). Homologous chromosomes pair, and crossing over occurs. It is divided into 5 stages: Leptotene: The chromosomes have replicated but individual chromatids are not visible. Zygotene. Instead of lining up on a metaphase plate, as in mitosis, chromosomes come together in pairs (2). Each chromosome in a pair is similar in structure (homologous), but would have come originally from different parents. The pairing of homologous chromosomes is also called synapsis and the resulting structure synaptic complex. Directly after initiation of the process the pairing spreads like a zipper across the whole length of the chromosome. Pachytene. During pachytene the pairing stabilizes. The number of synaptic complexes corresponds to the number of chromosomes in a haploid set of the respective species. The pairs are also called tetrad or bivalents. This state is marked by twisting of homologous pairs twist round each other and chromatids may cross over (3). Diplotene: The bivalents separate again. During this process it emerges that each chromosome is built of two chromatids, so that the whole complex harbours four strands during the separation. Normally the separation is not into 4, but the homologous chromosomes stick together at certain points, the chiasmata (sing. chiasma). Breaks occur at these cross-overs (or chiasmata, singular chiasma) and pieces of chromatid are exchanged (4). The chiasmata move towards the end of the chromatids in a process called Terminilization which may be viewed as a closed zipper which is being opened from points in the middle to either end. Diakinesis is the continuation of diplotene. The chromosomes condense and become more compact. It is usually difficult to demarcate both states. Metaphase I: The paired homologues align to form the metaphase plate Anaphase I: The members of a homologous pair separate and move to opposite poles. The two daughter cells thus have a haploid set of chromosomes, each of which has two chromatids and an undivided centromere. It is followed by the telophase, then by interkinesis (this state corresponds to the so-called quiescence or interphase state) MI begins with one diploid cell and ends with two haploid cells Meiosis II: The second of two divisions in meiosis, often abbreviated MII. It is similar in many respects to mitosis. After the alignment of the chromosomes at metaphase (metaphase II), the centromeres divide, the chromatids are separated from each other, and the new sister chromosomes move to opposite poles during anaphase (anaphase II). Next the chromatids are pulled apart in anaphase 2 to form four clusters of chromosomes in telophase 2. The nuclear envelopes reform around four haploid nuclei that will give rise to the micro- or megagametophyte. MII begins with two haploid cells and ends with four haploid cells As a result of the meiosis of a diploid cell, four haploid cells (gones) form, of which one (at egg cell formation) or all (at pollen formation) can develop into gametes Show animation of mitosis and meiosis from Freeman Genetics 2.0 Overview of Meiosis – for just 1 pair of chromosomes the two chromosomes of a homologous pair are individual chromosomes that were inherited from different parents; they are not usually connected to each other. both members of this single homologous pair of chromosomes in a diploid cell are replicated and the copies then sorted into four haploid daughter cells. sister chromatids are two copies of one chromosome, attached at the centromere; together they make up one duplicated chromosome Overview of meiosis: how meiosis reduces chromosome number. After the chromosomes replicate in interphase, the diploid cell divides twice, yielding four haploid daughter cells. This overview tracks just one pair of homologous chromosomes, which for the sake of simplicity are drawn in the condensed state throughout (they would not normally be condensed during interphase). The red chromosome was inherited from the female parent, the blue chromosome from the male parent. Mitosis vs Meiosis Meiosis I is called the reductional division because it halves the number of chromosome sets per cell—a reduction from two sets (the diploid state) to one set (the haploid state). The sister chromatids then separate during the second meiotic division, meiosis II, producing haploid daughter cells. The mechanism for separating sister chromatids is virtually identical in me iosis II and mitosis. Unique Events in Meiosis Three events are unique to meiosis, and all three occur during meiosis I: 1. Synapsis and crossing over. During prophase I, duplicated homologous chromosomes line up and become physically connected to form the synaptonemal complex ; this process is called synapsis . Genetic rearrangement between nonsister chromatids, known as crossing over , also occur during prophase I. The four chromatids of a homologous pair are visible in the light microscope as a tetrad . Each tetrad normally contains at least one X–shaped region called a chiasma (plural, chiasmata ), the physical manifestation of crossing over. Synapsis and crossing over normally do not occur during mitosis. 2. Tetrads on the metaphase plate. At metaphase I of meiosis, paired homologous chromosomes (tetrads) are positioned on the metaphase plate, rather than individual replicated chromosomes, as in mitosis. Crossing Over • Process by which two chromosomes exchange some portion of their DNA during prophase 1 of meiosis • Initiated before the synaptonemal complex develops in zygotene. Is completed near the end of prophase 1 • Crossover usually occurs when matching regions on matching chromosomes break and then reconnect to the other chromosome • Results in genetic recombination (an exchange of genes) Meiosis is often called "reduction division" because the genetic material is reduced - by half. Meiosis is extremely important not only for sexual reproduction, but also for creating the diversity upon which natural selection operates Life Cycle of Organisms The life cycle is the span of the life of an organism from the moment of fertilization to the time it reproduces. Don't confuse this with "life span" which extends beyond the time of reproduction Gamete formation in Mammals The entire process of producing gametes is called Gametogenesis. In males it is called Spermatogenesis and in females, Oogenesis. The organ in which Gametogenesis takes place is called the gonad. The male gonad is the testis; the female gonad the ovary. Spermatogenesis The diploid initial or primordial cells in the testis are called spermatogonia. A spermatogoium may develop into a primary spermatocyte which undergoes meiosis to produce four haploid spermatids. At maturation, the cytoplasm of each spermatid would have been pulled into a whip-like structure and is now called the spermatozoon. Each primary spermatocyte produces four spermatozoa. Oogenesis The diploid primordial cells in the ovary are called oogonia. An oogonium grows and stores a lot of food in its cytoplasm (yolk) to be used as food for the zygote when it is formed. This cell is the primary oocyte and it is this which undergoes meiosis. Two haploid nuclei are produced at the end of the first meiotic division. There is unequal distribution of cytoplasm during cytokinensis, and the larger cell is called secondary oocyte while the smaller one is called a polar body. The polar body may undergo the second meiotic division producing two polar bodies. The secondary oocyte also undergoes the second meiotic division, but again there is unequal distribution of cytoplasm in the cytokinensis which follows. The result is that the smaller cell becomes a polar body whilst the bigger one becomes the Ootid. By further growth and differentiation, the ootid becomes the mature female gamete called ovum or egg cell. The three polar bodies eventually degenerate. Therefore for every primary oocyte that enters meiosis, only one egg cell or ovum is produced in contrast to the four spermatozoa in males. Fusion (fertilization) causes two haploid cells (gametes) to create a unique diploid cell (zygote). The haploid stage is merely a requirement to make a zygote. Our haploid cells, once created, do "nothing". They just hang around waiting to fertilize something or to be fertilized! Our diploid (2n) cells undergo mitosis but our haploid (n) cells NEVER undergo mitosis. However, this isn't true of all organisms Reproduction in Plants Floral structure Terminology Reproduction can be asexual (from vegetative parts--non-gametic/ non-fertilized) or by sexual (requiring effective fertilization/ hybridization forming botanic seed) methods Alternation of sporophytic (2n) and gametophytic (n) generations In order to change from the sporophytic (2n) to gametophytic (n) generation, meiosis must take place. Among vascular plants, the diploid (2n) phase dominates the gametophyte (pollen or embryo sac – n) phase. Types of flowers Complete flowers - have sepals, petals, stamen, and pistil Incomplete flowers—lacking one of the above parts Perfect flowers--stamens and pistils are in the same floral structure - wheat Imperfect flower--stamen and pistil not in the same floral structure Monoecious ("one house")-stamens and pistils on the same plant (eg. maize, cassava) Dioecious ("two houses")-stamens and pistils on different plants. Ex. hemp, hops, buffalo grass, pawpaw, kiwi, nutmeg Flowers may either be solitary or may be grouped together to form an inflorescence Gametogenesis in Plants Formation of higher plants male and female gametes in Pollination and Fertilisation ANTHESIS: Maturation of the anther accompanied by the extension of the filament POLLINATION: Transfer of pollen grains from anther to stigma. • Method of transfer varies with crop • Pollen germinates on the stigma and the pollen tube enters the ovule via the micropyle • The generative nucleus divides -----> 2 male germ cells (gametes). These male nuclei enter the embryo sac FERTILIZATION: • One male gamete(sperm) fuses with the egg ---> zygote. The other male gamete unites with the two polar nuclei. This triple fusion -----> the primary endosperm nucleus. Mechanisms that promote Self Pollination • Cleistogamy • Stigma closely surrounded by anthers • Very few species are completely self pollinated • Rice, oats, wheat, barley, cowpea, soyabean, peanut, tomato, eggplant, okra etc Mechanisms that promote Cross Pollination • Dioecy • Monoecy • Dichogamy (protoandry and protogyny) • Self incompatibility • Male sterility • Heterostyly (pin and thrum flowers) Heterostyly Asexual Reproduction Vegetative Propagation No meiosis No genetic recombination New plants can be formed from – – – – – – – Stolons Rhizomes Tubers Offset buds on corms and bulbs Suckers Bulbils [bulb-like propagules in inflorescence] Vivipary [tiny plantlets growing on the parent plant] Tissue culture cloning Tissue Culture Cloning – Growth of a plantlet from a few meristem cells cultured on a chemical medium – A single plant can be cloned into thousands of copies that will continue to grow when planted in soil – Orchids and certain pine trees used in mass plantings are propagated this way Apomixis • Reproduction in plants where meiosis and fertilization do not occur – Normal seed is set although no sexual fusion of gametes takes place – Genotypes of the progeny are very similar, if not identical, to the (female) parent. – Embryo sac is unreduced i.e. it contains diploid nuclei and so there is no need for fertilization to restore diploidy • Example – citrus trees – In one form, an egg is formed with 2N chromosomes and develops without being fertilized – In another form, the cells of the ovule (2N) develop into an embryo instead of, or in addition to, the fertilized egg Mendelian Inheritance Mendel published a small work with the title: Experiments in Plant Hybridization in 1866 This work remained obscured, and was rediscovered in 1900 Gregor Mendel (1822-1884) Mendel’s Experiments 1. Mendel developed pure lines of pea Pure Line - a population that breeds true for a particular trait e.g., all seeds are either round or wrinkled, flowers purple or white for many generations. This was an important innovation because any non-pure (segregating) generation would and did confuse the results of genetic experiments. 2. Counted his results and kept statistical notes – this is essential for data analysis Mendel had pure parental lines (P) that differed in single characters or traits Flower colour: Purple vrs white Seed colour: Green vrs yellow Seed shape: Round vrs wrinkled Plant height: Tall vrs dwarf Mendel crossed parents differing in these characteristics and obtained the following in the first offspring (F1 or first filial generation): P1 = Purple; P2 = white flowers P1 = yellow; P2 = green seeds F1 hybrids = All purple F1 hybrids = All yellow P1 = Round P2 = wrinkled seeds P1 = Short P2 = Tall plants F1 hybrid = All tall Purple, white, yellow, green, round, wrinkled, tall, short etc are what the eye sees, and is termed the phenotype. Phenotype - literally means "the form that is shown"; it is the outward, physical appearance of a particular trait. The phenotype is the appearance of an individual that is based on an underlying genotype and on the influence that the environment exerts F1 hybrids = All round A genotype is the specific combination of the alleles of a cell. The term means either the whole genome or (the sense it usually has) certain genes We always see only one of the two parental phenotypes in the F1 generation The Allele Concept Allele - one alternative form of a given allelic pair; purple and white are the alleles for the flower colour of a pea plant; more than two alleles can exist for any specific gene, but only two of them will be found within any diploid individual Allelic pair - the combination of two alleles which comprise the gene pair Homozygote - an individual which contains only one allele at the allelic pair; for example DD is homozygous dominant and dd is homozygous recessive; pure lines are homozygous for the gene of interest Dominant - the allele that expresses itself at the expense of an alternate allele; an allele that determines the phenotype in a heterozygous condition Recessive - an allele whose expression is suppressed in the presence of a dominant allele; the phenotype that disappears in the F1 generation from the cross of two pure lines and reappears in the F2 generation. A recessive allele displays no influence on the phenotype in heterozygous individuals Homozygote - an individual which contains only one allele at the allelic pair; for example DD is homozygous dominant and dd is homozygous recessive; pure lines are homozygous for the gene of interest Heterozygote - an individual which contains one of each member of the gene pair; for example the Dd heterozygote Monohybrid cross - a cross between parents that differ at a single gene pair (usually AA x aa) Monohybrid - the offspring of two parents that are homozygous for alternate alleles of a gene pair Remember --- a monohybrid cross is not the cross of two monohybrids The phenotype is the appearance of an individual that is based on an underlying genotype and on the influence that the environment exerts Mendel then crossed the F1 to themselves (selfed the F1) He observed that white flowers that was absent in the F1 appeared in the F2 in a ratio of 3 purple flowers to one white flower i.e., a phenotypic ratio of 3:1 MENDEL's first law is the principle of segregation. It states that during gamete formation each member of the allelic pair separates from the other member to form the genetic constitution of the gamete. The individuals of the F2 generation are therefore not uniform because the traits segregate (separate out - different types are visible). The characteristics of the parental generation do always occur at a certain ratio. Depending on a dominant-recessive or an intermediate crossing, they segregate in the ratio 3:1 or 1:2:1 Law of Segregation Genotype vs. Phenotype = appearance = the allele combination Confirmation of Mendel’s first law The Testcross This is the cross of any individual to a homozygous recessive individual; used to determine if the individual is homozygous dominant or heterozygous The F1 phenotypic ratios tell whether the dominant phenotype is homozygous (no segregation) or heterozygous ( ratio of 1:1) Confirmation of Mendel’s first law: The F3 Mendel’s second law Mendel also performed crosses in which he followed the segregation of two genes e.g., Yellow and round seeds x Green and wrinkled seeds. The dominance relationship between alleles for each trait was already known to Mendel when he made this cross Dihybrid cross - a cross between two parents that differ by two pairs of alleles (AABB x aabb) Dihybrid - an individual heterozygous for two pairs of alleles (AaBb) Parental Cross: Yellow, Round Seed x Green, Wrinkled Seed F1 Generation: All yellow, round F2 Generation: 9 Yellow, Round, 3 Yellow, Wrinkled, 3 Green, Round, 1 Green, Wrinkled Let's now look at the cross using gene symbols Mendel selfed the F1 and obtained individuals as shown in Punett Square below: Female Gametes gW GW Gw GW GGWW GGWw GgWW GgWw Gw Yellow, round GGWw Yellow, round GGww Yellow, round GgWW Yellow, round Ggww gW Yellow, round GgWW Yellow, wrinkled GgWw Yellow, round ggWW Yellow, wrinkled ggWw gw Yellow, round GgWw Yellow, round Ggww Green, round ggWw Green, round ggww Yellow, round Yellow, wrinkled Green, round Green, wrinkled Male Gametes gw The phenotypes and general genotypes from this cross can be represented in the following manner: Phenotype General Genotype 9 Yellow, Round Seed G_W_ 3 Yellow, Wrinkled Seed G_ww 3 Green, Round Seed ggW_ 1 Green, Wrinkled Seed ggww The results of this experiment led Mendel to formulate his Third law. Mendel's Second Law - the law of independent assortment; during gamete formation the segregation of the alleles of one allelic pair is independent of the segregation of the alleles of another allelic pair It does inevitably cover the case that new combinations of genes, that were not existing before can arise. In MENDEL's experiment these are the combinations: Yellow wrinkled seeds; Green round seeds PUNNETT-Square: The scheme shows the genotypes of the P-, F1and F2-generation of a dihybrid hereditary path. This kind of representation was introduced by the British geneticist R. C. PUNNETT at the beginning of 20th century Law of Independent Assortment Note: MENDEL's fundamental work was forgotten for 35 years. It became known in 1900. The German C. CORRENS, the Dutchman HUGO de VRIES and the Austrian ERICH von TSCHERMAK-SEYSENEGG are regarded as its rediscoverers. Their articles were all published at nearly the same time in 1900. They heard first of MENDEL's work, when their own work was nearly finished. H. de VRIES writes apologetically: "This important work is hardly cited, so that I myself did not get to know it before I had finished most of my own experiments and had concluded the same laws as are mentioned in the text." C. CORRENS recognized furthermore that not all characters can be freely combined, but that some of them are coupled and are thus always inherited together Mendel’s work is today viewed as the fundament of modern genetics. The chromosome theory confirmed Mendel’s work Complications to Mendelian Genetics 1. Gene actions • Intra-allelic interactions » Incomplete or partial dominance » Codominance » Over-dominance • Inter-allelic interactions » Epistasis » Pleiotrophy 2. Sex linked inheritance 3. Linkage Mendel’s Dominance • Mendel’s rule of dominance was complete dominance – Homozygous dominant and heterozygous individuals had indistinguishable phenotypes – Example: Both PP and Pp plants have the dominant PURPLE phenotype (P=purple and p=white flowers) Incomplete Dominance • Offspring have an appearance somewhat in between the phenotypes of the two parents – “Mixed” – Blended R R r Rr Rr F1 generation r Rr Rr All Rr = pink (heterozygous pink) Incomplete Dominance • Incomplete dominance occurs when one allele is partially dominant over the other – thus, the two alleles have unequal influence on the phenotype Codominance • BOTH alleles are expressed equally in heterozygous individuals • Neither allele is dominant over the other – Example: blood type • Determined by whether or not you have A or B proteins • IA = A protein • IB = B protein • I = no protein Codominance Codominance Problem • Example:homozygous male Type B (IBIB) • x heterozygous female Type A (IAi) IB IB IA IAIB IAIB i IBi IBi 1/2 = IAIB 1/2 = IBi Another Codominance Problem Example: male Type O (ii) x female type AB (IAIB) IA IB i IAi IBi i IAi IBi 1/2 = IAi 1/2 = IBi Codominance • Question: If a boy has a blood type O and his sister has blood type AB, what are the genotypes and phenotypes of their parents? boy - type O (ii) X girl - type AB (IAIB) Codominance • Answer: IA IB i i IAIB ii Parents: genotypes = IAi and IBi phenotypes = A and B Sex-linked Inheritance • Traits (genes) located on the sex chromosomes • Sex chromosomes are X and Y –XX genotype for females –XY genotype for males • Many sex-linked traits carried on X chromosome Sex – Linked Traits • Example: Colour blindness – If the mother carries the colour blindness gene on her X chromosome, her son could get it. – As long as one X chromosome is ok, a female will not X y express the trait cX X X y C X X XX Xy Sex-linked Traits Example: Colorblindness Sex Chromosomes Colorblindness XX chromosome - female Xy chromosome - male Epistasis Epistatic genes override or mask the phenotype of a second gene. Epistasis is not dominance. Compare the definitions: Epistasis One gene masks the expression of a different gene for a different trait Dominance One allele masks the expression of another allele of the same gene Classical Epistatic Ratios • About 6 different epistatic gene actions have been observed 1. Complementary gene action (9:7): also known as duplicate recessive epistasis 2. Duplicate gene action (15:1): a.k.a duplicate dominant epistasis 3. Recessive suppressors (13:3): a.k.a dominant and recessive epistasis 4. Additive gene action (9:6:1) 5. Dominant epistasis (12:3:1) 6. Recessive epistasis (9:3:4) Pleiotropy One gene causes multiple effects on a phenotype, i.e. the control of two or more characters by a single gene Sickle cell anemia: one mutant gene, many symptoms Single amino acid substitution in the hemoglobin protein Pain, stroke, leg ulcers, bone damage, jaundice, gallstones, lung damage, kidney damage, eye damage, anemia, delayed growth LINKAGE • T. H. MORGAN’S LAWS (1911): • Genes occur chromosomes • Linked genes chromosome in a are linear on order the on same • Genes can be exchanged between homologous chromosomes during meiosis • The closer genes are located on a chromosome, the less likely they will separate and recombine in meiosis Genes on the same chromosome are linked Gene loci Dominant a P P Genotype: PP b a aa Homozygous Homozygous for the for the dominant allele recessive allele allele B Bb Recessive allele Heterozygous Figure 9.9 GENETIC RECOMBINATION • If two genes are close together, they will not independently enough assort • If they are not close together, recombination or crossing over may occur to separate them • Linkage types – Two possible configurations • cis: • trans: A B // a b A b // a B MOLECULAR GENETICS: THE CHEMICAL BASIS OF HEREDITY Discovery of DNA as the Hereditary Material • Nucleic Acids (DNA and RNA) were discovered in 1869 by Friedrich Mieschner as a substance contained within cells • During the ’30s & 40’s proteins rather than DNA was thought to hold genetic information Griffith’s Transformation Experiment 1928 Attempting to develop a vaccine Isolated two strains of Streptococcus pneumoniae Rough strain was harmless Smooth strain was pathogenic Transformation 1. Mice injected with live cells of harmless strain R. 2. Mice injected with live cells of killer strain S. 3. Mice injected with heat-killed S cells. 4. Mice injected with live R cells plus heatkilled S cells. Mice live. No live R cells in their blood. Mice die. Live S cells in their blood. Mice live. No live S cells in their blood. Mice die. Live S cells in their blood. Transformation What happened in the fourth experiment? The harmless R cells had been transformed by material from the dead S cells Descendents of the transformed cells were also pathogenic Why? Oswald & Avery’s Experiment What is the transforming material? Cell extracts treated with proteindigesting enzymes could still transform bacteria Cell extracts treated with DNA-digesting enzymes lost their transforming ability Concluded that DNA, transforms bacteria not protein, Bacteriophages Viruses that infect bacteria Consist of protein and DNA Inject their hereditary material into bacteria bacterial cell wall cytoplasm plasma membrane Hershey & Chase’s Experiments • Created labeled bacteriophages – Radioactive sulfur – Labels Proteins – Radioactive phosphorus – Labels Nucleic Acids • Allowed labeled viruses to infect bacteria • Asked: Where are the radioactive labels after infection? What is DNA? • Deoxyribonucleic acid (DNA) is a Nucleic Acid • Nucleic acids are polymers of Nucleotides • A nucleotide consists of three molecules – A Pentose or 5-carbon sugar – A nitrogenous base – Phosphate group • There are four N-bases in DNA – Adenine, Guanine, Thymine, Cytosine Composition of DNA • Chargaff showed: – Amount of adenine relative to guanine differs among species – Amount of adenine always equals amount of thymine and amount of guanine always equals amount of cytosine A=T and G=C Rosalind Franklin’s Work • Was an expert in X-ray crystallography • Used this technique to examine DNA fibers • Concluded that DNA was some sort of helix Structure of DNA by J. Watson & F. Crick (1953) • Carbon 1 (C1) is where the base is attached. • Carbon 2 (C2) tells you if it is a ribose or deoxyribose. In deoxyribose, oxygen at C2 is missing. • Carbon 3 (C3) is the point of attachment for more nucleotides through a phospho-diesther bond • Carbon 4 (C4) completes the ring via an oxygen (O) which bridges to the carbon 1 (C1). Carbon 5 (C5) hangs away from the ring and is the point of attachment for its phosphate(s). KNUST 137 • DNA is a double stranded helix • The two strands are Antiparallel • Strands are held together hydrogen bonds between bases • A pairs with T, and C with G by Nucleotide Structure DNA is Antiparallel Base-pairing rule The four bases of DNA are: Adenine (A) Guanine (G) Thymine (T) Cytosine (C) Adenine always hydrogen bonds with Thymine (A-T) Guanine always hydrogen bonds with Cytosine (G-C) These bonding patterns are called base pairings (bp) DNA Replication • Before mitosis and meiosis, all of the DNA in the cell must be copied or replicated during the Synthesis phase of Interphase • How does this happen? DNA Replication What is a gene? • A gene is a piece of DNA consisting of coding (exons) and non-coding (introns) base sequences with the inherent ability to be transcribed and translated to produce a protein KNUST 144 • Thus, a gene locus for any character or trait (eg. Flower colour, seed coat colour, disease resistance, dwarfism, etc) on any chromosome, can be viewed as a code of genetic information written with the four bases; A, C, G, T. • Alleles actually emanate from differences in base sequences on homologous chromosomes caused by mutations, resulting in different proteins being formed, hence different phenotypes. How are Genes Expressed? • Gene expression involves four important processes –Transcription –RNA processing –Translation –Protein processing • Transcription precedes translation during gene expression, and takes place in the nucleus, whereas translation occurs on the ribosomes, in the cytoplasm Transcription • It is the first step in the expression of genes • It is the process by which information on the DNA is copied by a related chemical bearer RNA • Genes must remain on chromosomes for replication, repairs and transmission, but at the same time the genes must be able to direct all cell activities notably protein synthesis • Transcription of genes is superficially similar to DNA replication • For, transcription to take place, an enzyme called DNA dependent RNA Polymerase binds to one of the strands of the DNA at a starting point referred to as PROMOTER SEQUENCE • Only one strand of the DNA double helix serves as a template for RNA • The RNA polymerase then matches complementary nucleotides along the DNA template according to the base pairing rules • The difference however is that Uracil replaces Thymine in the matching of complementary bases • The paired bases are then polymerised to form a single stranded RNA molecule Overview of transcription The RNA formed (transcript) then peels off from the DNA, and exits the nucleus through the nuclear pore into the cytoplasm for translation to proceed In molecular terms, a gene is therefore a unit of Translation (Protein Synthesis) • Three types of RNA are mainly found in living cells, and all these three are produced via transcription – Messenger RNA (mRNA) – Transfer RNA (tRNA) – Ribosomal RNA (rRNA) • However, it is ONLY mRNA that is translated during protein synthesis • mRNA undergoes a post-transcriptional processing known as SPLICING, prior to translation • During splicing, all non-coding sequences (introns) in the mRNA transcript are removed by the enzyme spliceosome, leaving only coding sequences (Exons) • Translation involves the conversion of the message carried by the mRNA to polypeptides (proteins) • when the mRNA exits the nucleus after transcription, it enters the cytoplasm and attaches itself to the ribosome • The nitrogenous bases on the mRNA are picked in groups of three bases by the ribosome. • Each group of three bases is known as a CODON • Each codon species an amino acid • There is an interaction between mRNA, tRNA and rRNA during protein synthesis • tRNA interacts with amino acids and influences their correct insertion into the polypeptide chain • The tRNA molecule also carries a group of three bases known as ANTICODON, and each anticodon complements a codon on the mRNA • As the ribosome picks the codons on the mRNA, the tRNA molecule with the corresponding anticodon moves into position, carrying the amino acid specified by the codon • As the next codon is picked by the ribosome, the tRNA molecule with the complementing anticodon also moves into position with the specific amino acid for the codon. • A peptide bond joins the both amino acid molecules, and by this process the polypeptide chain grows longer until a STOP codon (UGA, UAG and UAA) is reached on the mRNA Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display THE GENETIC CODE Special codons: AUG (which specifies methionine) = start codon UAA, UAG and UGA = termination, or stop, codons The code is degenerate More than one codon can specify the same amino acid For example: GGU, GGC, GGA and GGG all code for lysine The code is nearly universal Only a few rare exceptions have been noted An overview of gene expression PEPTIDE BONDS MUTATIONS AND CHROMOSOMAL VARIATION MUTATIONS • A mutation is a sudden heritable change in the genome of an organism that can not be accounted for by segregation and recombination • It is the ultimate source of new alleles in the populations of living organisms; it creates new alleles that could be acted upon by segregation and recombination to increase variability in the population • Mutations can occur spontaneously under natural conditions or could be deliberately induced artificially using mutagenic agents such as irradiation and chemicals • The new alleles created by mutations could be either dominant or recessive, resulting in dominant and recessive mutations respectively • Most mutations are however recessive and sometimes lethal or deleterious eg. Sickle cell anaemia (a recessive lethal mutation) • Mutations can also be classified based on the type of cell involved, producing somatic or germinal mutations • Mutations can be broadly grouped into two types: –Micro/point/gene mutations –Macro mutations Micro/Point/Gene Mutations • These are mutations that involve changes in the chemical structure (coding sequences) of a gene via additions, substitutions or deletions of nitrogenous base sequences Types of Point Mutations Missense mutation – changes amino acid Nonsense mutations – creates stop codon Frameshift mutation– alters remainder of reading frame results in completely different amino acid sequence. Base Substitutions • Transitions – – – – pyrimidine replaces pyrimidine - C to T or T to C purine replaces purine – G to A or A to G GC changed to A=T or vice versa Most common base change • Transversion – purine replaces pyrimidine or vice versa – G to C or T – A to C or T – Rare but classical example is the sickle cell anaemia – caused by a point mutation in the gene for producing haemoglobin. A transversion base substitution of ‘T’ with ‘A’ in the sixth amino acid, changed it from glutamic acid to valine in sicklers MACRO OR CHROMOSOMAL MUTATIONS 1. Variation in chromosome number 1.1. Euploidy/Polyploidy 1.2. Aneuploidy 2. Variation in chromosome structure (chromosomal aberrations) 2A. Change in the amount of genetic information EUPLOIDY EUPLOID: Chromosome number is changed to exact multiple of the basic set Polyploids are euploids in multiple of basic set of chromosome – – – – – – – • Diploid Triploid Tetraploid Pentaploid Hexaploid Septaploid Octoploid 2x 3x 4x 5x 6x 7x 8x EUPLOIDS may be – AUTOPLOIDS: Having Duplicate genome of same species – Autotetraploid: Having Duplicate genome of same diploid species – ALLOPLOIDS: Having Duplicate genome of different species Allotetraploid or amphidiploid: Having Duplicate genome of different species Ploidy Levels in Different crops Species Crop Basic Haploid Chromosom (Gametic) e Number Number (n) (x) Somatic (Diploid) Chromosome number (2n) Avena strigosa Oats 7 7 2n = 2x= 14 Avena barbata Oats 7 14 2n = 4x= 28 Avena sativa Oats 7 21 2n = 6x= 42 Gossypium arboreum Cotton 13 13 2n = 2x= 26 Gossypium hirsutum Cotton 13 26 2n = 4x= 52 Triticum monococum Einkorn Wheat 7 7 2n = 2x= 14 Triticum turgidum Durum Wheat 7 14 2n = 4x= 28 Triticum aestivum BreadW heat 7 21 2n = 6x= 42 ANEUPLOIDY Chromosome number is changed by addition or deletion of specific chromosomes Nondisjunction • Chromosomes fail to separate • Results in gametes and zygote with an abnormal chromosome number • Most aneuploidy result from errors in meiosis Nondisjunction during meiosis Chromosome number in gametes: Extra chromosome (n + 1) Extra chromosome (n + 1) Missing chromosome (n – 1) Missing chromosome Chromosomes align at metaphase I Nondisjunction at anaphase I Alignments at metaphase II Anaphase II (n – 1) Fig. 3-2, p. 45 Effects of Changes in Chromosome Numbers • May cause birth defects or fetal death • Monosomy of any autosome is fatal • Only a few trisomies result in live births AUTOSOMAL TRISOMIES 1. Trisomy 13: Patau Syndrome (47,+13) • 1/15,000 • Survival: 1–2 months • Facial, eye, finger, toe, brain, heart, and nervous system malformations Patau Syndrome 2. Trisomy 13: Edwards Syndrome (47,+18) • 1/11,000, 80% females • Survival: 2–4 months • Small, mental disabilities, clenched fists, heart, finger, and foot malformations • Die from heart failure or pneumonia Edwards Syndrome 3. Trisomy 21: Down Syndrome (47,+21) • 1/800 (changes with age of mother) • Survival up to age 50 • Leading cause of childhood mental retardation and heart defects • Wide, flat skulls; eyelid folds; large tongues; physical, mental, development retardation • May live rich, productive lives Down Syndrome Aneuploidy in Sex Chromosomes • Turner syndrome (45,X): monosomy of X chromosome • Klinefelter syndrome (47,XXY) • Jacobs syndrome (47,XYY) Sex Chromosome Trisomies Sex Chromosome Trisomies Sex Chromosome Trisomies Turner Syndrome (45,X) • Survival to adulthood • Female, short, wide-chested, undeveloped ovaries, possible narrowing of aorta • Normal intelligence • 1/10,000 female births, 95–99% of 45,X conceptions die before birth Turner Syndrome Klinefelter Syndrome (47,XXY) • Survival to adulthood • Male • Features do not develop until puberty, usually sterile, may have learning disabilities • 1/1,000 males XYY or Jacobs Syndrome (47,XYY) • Survival to adulthood • Average height, thin, personality disorders, some form of mental disabilities, and adolescent acne • Some may have very mild symptoms • 1/1,000 male births XYY Syndrome Structural Changes in Chromosomes DUPLICATIONS p. 47 DELETIONS OR DEFICIENCIES p. 47 INVERSIONS p. 47 TRANSLOCATIONS p. 47 STATISTICS AS APPLIED IN GENETICS PROBABILITY AND STATISTICS • The laws of inheritance can be used to predict the outcomes of genetic crosses • For example – Animal and plant breeders are concerned with the types of offspring produced from their crosses – Parents are interested in predicting the traits that their children may have • This is particularly important in the case of families with genetic diseases Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-52 PROBABILITY AND STATISTICS • Of course, it is not possible to definitely predict what will happen in the future • However, genetic counselors can help couples by predicting the likelihood of them having an affected child – This probability may influence the couple’s decision to have children or not Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-53 Probability • The probability of an event is the chance that the event will occur in the future Number of times an event occurs • Probability = Total number of events • For example, in a coin flip Pheads = 1 heads (1 heads + 1 tails) = 1/2 = 50% Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-54 • The accuracy of the probability prediction depends largely on the size of the sample • Often, there is deviation between observed and expected outcomes • This is due to random sampling error – Random sampling error is large for small samples and small for large samples • For example – If a coin is flipped only 10 times • It is not unusual to get 70% heads and 30% tails – However, if the coin is flipped 1,000 times • The percentage of heads will be fairly close to the predicted 50% value Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-55 • Probability calculations are used in genetic problems to predict the outcome of crosses • To compute probability, we can use three mathematical operations – Sum rule – Product rule – Binomial expansion equation Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-56 Sum rule • The probability that one of two or more mutually exclusive events will occur is the sum of their respective probabilities • Consider the following example in mice • Gene affecting the ears • Gene affecting the tail – De = Normal allele – Ct = Normal allele – de = Droopy ears – ct = Crinkly tail Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-57 • If two heterozygous (Dede Ctct) mice are crossed • Then the predicted ratio of offspring is – 9 with normal ears and normal tails – 3 with normal ears and crinkly tails – 3 with droopy ears and normal tails – 1 with droopy ears and crinkly tail • These four phenotypes are mutually exclusive – A mouse with droopy ears and a normal tail cannot have normal ears and a crinkly tail • Question Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-58 • Applying the sum rule – Step 1: Calculate the individual probabilities P(normal ears and a normal tail) = 9 (9 + 3 + 3 + 1) = 9/16 P(droopy ears and crinkly tail) = 1 (9 + 3 + 3 + 1) = 1/16 – Step 2: Add the individual probabilities 9/16 + 1/16 = 10/16 • 10/16 can be converted to 0.625 – Therefore 62.5% of the offspring are predicted to have normal ears and a normal tail or droopy ears and a crinkly tail Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-59 Product rule • The probability that two or more independent events will occur is equal to the product of their respective probabilities • Note – Independent events are those in which the occurrence of one does not affect the probability of another Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-60 • Consider the disease congenital analgesia – Recessive trait in humans – Affected individuals can distinguish between sensations • However, extreme sensations are not perceived as painful – Two alleles • P = Normal allele • p = Congenital analgesia • Question – Two heterozygous individuals plan to start a family – What is the probability that the couple’s first three children will all have congenital analgesia? Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-61 • Applying the product rule – Step 1: Calculate the individual probabilities • This can be obtained via a Punnett square P(congenital analgesia) = 1/4 – Step 2: Multiply the individual probabilities 1/4 X 1/4 X 1/4 = 1/64 • 1/64 can be converted to 0.016 – Therefore 1.6% of the time, the first three offspring of a heterozygous couple, will all have congenital analgesia Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-62 Binomial Expansion Equation • Represents all of the possibilities for a given set of unordered events P= n! x! (n – x)! px qn – x • where – p = probability that the unordered number of events will occur – n = total number of events – x = number of events in one category – p = individual probability of x Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-63 • Note: – p+q=1 – The symbol ! denotes a factorial • n! is the product of all integers from n down to 1 – 4! = 4 X 3 X 2 X 1 = 24 – An exception is 0! = 1 • Question – Two heterozygous brown-eyed (Bb) individuals have five children – What is the probability that two of the couple’s five children will have blue eyes? Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-64 • Applying the binomial expansion equation – Step 1: Calculate the individual probabilities • This can be obtained via a Punnett square P(blue eyes) = p = 1/4 P(brown eyes) = q = 3/4 – Step 2: Determine the number of events • n = total number of children = 5 • x = number of blue-eyed children = 2 – Step 3: Substitute the values for p, q, x, and n in the binomial expansion equation Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-65 n! P= x! (n – x)! P= P= 5! 2! (5 – 2)! px qn – x (1/4)2 (3/4)5 – 2 5X4X3X2X1 (2 X 1) (3 X 2 X 1) P = 0.26 (1/16) (27/64) or 26% • Therefore 26% of the time, a heterozygous couple’s five children will contain two with blue eyes and three with brown eyes Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-66 The Chi Square Test • A statistical method used to determine goodness of fit – Goodness of fit refers to how close the observed data are to those predicted from a hypothesis • Note: – The chi square test does not prove that a hypothesis is correct • It evaluates whether or not the data and the hypothesis have a good fit Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-67 The Chi Square Test • The general formula is c2 = S (O – E)2 E • where – O = observed data in each category – E = observed data in each category based on the experimenter’s hypothesis S = Sum of the calculations for each category Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-68 • Consider the following example in Drosophila melanogaster • Gene affecting wing shape – c+ = Normal wing – c = Curved wing • Note: • Gene affecting body color – e+ = Normal (gray) – e = ebony – The wild-type allele is designated with a + sign – Recessive mutant alleles are designated with lowercase letters • The Cross: – A cross is made between two true-breeding flies (c+c+e+e+ and ccee). The flies of the F1 generation are then allowed to mate with each other to produce an F2 generation. 2-69 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display • The outcome – F1 generation • All offspring have straight wings and gray bodies – F2 generation • 193 straight wings, gray bodies • 69 straight wings, ebony bodies • 64 curved wings, gray bodies • Applying the chi square test • 26 curved wings, ebony bodies – Step 1: total Propose • 352 fliesa hypothesis that allows us to calculate the expected values based on Mendel’s laws • The two traits are independently assorting Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-70 – Step 2: Calculate the expected values of the four phenotypes, based on the hypothesis • According to our hypothesis, there should be a 9:3:3:1 ratio on the F2 generation Phenotype Expected Expected number probability straight wings, 9/16 9/16 X 352 = 198 gray bodies straight wings, ebony bodies curved wings, gray bodies 3/16 3/16 X 352 = 66 3/16 3/16 X 352 = 66 curved wings, ebony bodies 1/16 1/16 X 352 = 22 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-71 – Step 3: Apply the chi square formula c2 = (O1 – E1)2 + E1 (193 – 198)2 2 c = 198 (O2 – E2)2 + E2 + (69 – 66)2 66 (O3 – E3)2 + E3 + (64 – 66)2 66 (O4 – E4)2 E4 + (26 – 22)2 22 c2 = 0.13 + 0.14 + 0.06 + 0.73 c2 = 1.06 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-72 • Step 4: Interpret the chi square value – The calculated chi square value can be used to obtain probabilities, or P values, from a chi square table • These probabilities allow us to determine the likelihood that the observed deviations are due to random chance alone – Low chi square values indicate a high probability that the observed deviations could be due to random chance alone – High chi square values indicate a low probability that the observed deviations are due to random chance alone – If the chi square value results in a probability that is less than 0.05 (ie: less than 5%) 2-73 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display • Step 4: Interpret the chi square value – Before we can use the chi square table, we have to determine the degrees of freedom (df) • The df is a measure of the number of categories that are independent of each other • df = n – 1 – where n = total number of categories • In our experiment, there are four phenotypes/categories – Therefore, df = 4 – 1 = 3 – Refer to Table 2.1 Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-74 1.06 2-75 • Step 4: Interpret the chi square value – With df = 3, the chi square value of 1.06 is slightly greater than 1.005 (which corresponds to P= 0.80) – A P = 0.80 means that values equal to or greater than 1.005 are expected to occur 80% of the time based on random chance alone – Therefore, it is quite probable that the deviations between the observed and expected values in this experiment can be explained by random sampling error Copyright ©The McGraw-Hill Companies, Inc. Permission required for reproduction or display 2-76 • For quantitative characters, we can also calculate measures of central tendency like mean, mode and median, as well as measures of dispersion such as range, variance, standard deviation, coefficient of variation, range etc.