Lecture notes, lecture all - Genetics PDF

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MCB 2410—GENETICS CLASS NOTES: LECTURE ONE:  Grade Division- 30% each (3 exams, quiz average where best 3 are taken; 1 drop) and 10% of participation during discussion or participation classes. o Grades are averaged, but each component is graded independently. o Key terms and practice problems assigned (but not graded).  (CH. ONE) Importance of Genetics- it is the foundation of all biology and all of life—all organisms use genetic systems that have fundamental similarities. o Genomics- the study that explains things such as how the sperm and egg meet and then develop into an organism o Genetics has an underlying role in development (i.e. mitosis and meiosis), health and disease (i.e. heart disease, alcoholism, diabetes) and evolution.  Evolution- a lot of speciation or a lot of the process is rearrangement of the genetic material or using the genetic material that exists there.  Two basic types of Cells- this include prokaryotes and eukaryotes o Prokaryotes- a type of bacteria; single-celled organisms that do not have compartments in their cells so their components and DNA are free-floating in the cell (cytoplasm) o Eukaryotes- has compartmentalized cells; often multicellular organisms (i.e. humans and mice), but you can also have things such as yeast  There are mitochondria (the powerhouse), which is similar to chloroplast (responsible for photosynthesis) in plants.  Mitochondria and chloroplasts have their own DNA  Nucleus- contains the genome or the nucleic DNA (deoxyribose nucleic acid)—the nucleus contains the full genome of the organism  Nuclear genome- contains the DNA and the proteins that package the DNA— i.e. the human genome is 300 million letters long, meaning we have enough DNA to get to the moon and back 3x.  Eukaryotic DNA- it is a long, linear molecule where information is encoded in the linear sequence of DNA bases; it is a double helix o The four possible letters consist of: A (adenine), C (cytosine), T (thymine) and G (guanine). o The Central Dogma- the only way the information flows is from DNA  RNA  Protein—information is encoded in the DNA, but the information is one-directional flow and the DNA is the storage house, the DNA is a messenger molecule that gets the information out to the cytoplasm so that the ribosomes can make the protein. o The way that information gets used is dependent upon the way that the information is packaged up on the protein—i.e. whether you can turn it into RNA to form into a protein. o Chromosome- a linear piece of DNA and each eukaryotic species have a characteristic number of chromosomes.  Ploid- refers to a number of chromosomes—i.e. Humans are diploid (2N), meaning they have two copies of each chromosome.  Autosomes- humans have 22 pairs  Sex chromosomes- humans have one pair; depending on whether you are a male (XY) or female (XX)  Allele- different variations of a gene; coded for by the locus (site of gene on the chromosome)  We all have the same genes, but subtle differences or copies of the gene.  Karyotype- layout of chromosomes  Chromosome structure- consists of telomeres (ends of DNA that protect it), centromere (or central constriction; plays a role when you make a copy of the DNA to separate it)  Replication of the chromosome- you get sister chromatids (referred to as a dyad), but it is still only one chromosome so to understand how many chromosomes you are looking at, you can count the centromeres

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P arm- the petite arm (top arm) Q arm- the bottom arm that is usually longer. Spindle fibers- attaches to the protein structure on the chromosomes (kinetochore) to separate the structure and one copy of the chromosome will go to different cells.  Metacentric- centromere at center  Submetacentric- slightly off center  Acrocentric- very close to the top of the chromosome  Telocentric- seems as if there is only a bottom o Undergoes Transcription to become RNA  Part of all eukaryotic cells that has its only nuclear envelope to support and protect it from meshing with other components of the cell. Most of the cellular activity occurs outside of the nucleus. Ribosomes- the component of a eukaryotic cell that is responsible for the production of proteins. Cell Division- successful replication and division of DNA—losing control of cell division could result in cancer (i.e. the continuous division or replication) or aneuploidy of the cell.  Two types of cell division- mitosis and meiosis o Mitosis- make two genetically identically daughter cells of somatic cells (i.e. germ line)—start off with parent cell  replication  2 cells  Occurs in all somatic cells.  Interphase- the nuclear membrane is present and chromosomes are relaxed—the DNA are long, linear molecules that are relaxed and there is no condensed, visible structure to indicate differences between DNA (still well structured)—“resembles spaghetti”  Prophase-chromosomes condense and each chromosome posses two chromatids; also, the mitotic spindle forms—the fibers form from a structure called the centrosome; there is a condensing of the DNA  Prometaphase- the nuclear membrane disintegrates and spindle microtubules attach to chromatids.  Metaphase- chromosomes are most condensed— chromosomes line up on the metaphase plate (spindle fiber attachment to the kinetochore).  Anaphase- sister chromatids separate and move toward opposite poles; there is brief period of doubling the amount of chromosomes as you are supposed to have.  Telophase- when the chromatids have reached the poles, the nuclear membrane reforms and the chromosomes relax  Microtubules in Mitosis- originate from centrosomes at each pole of the cell; composed of tubulin subunits and attach to the kinetochore of each sister chromatid. o Meiosis- the goal is first to make haploid gametes or sex cells (half the amount of DNA)—parent cell  replication  2 cells  ends with 4 daughter cells.  Gametogenesis- the production of sex cells—MAKE SURE TO LOOK AT SPECIFIC GAMETE FORMATION IN MAMMALS CHART!!!  There is reductional division in Meiosis I (2N1N) and equational division in Meiosis II (1N2N).  The Life Cycle of a Cell: o Interphase- the phase that consists of cell growth  G1- cell grows and continues on its regular business  G0- a non-dividing phase  G1/ S checkpoint- checks for correct proteins and if replication is possible  S phase- consists of synthesis and DNA replication

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G2- cell is preparing for mitosis G2/ M checkpoint- is there any DNA damaged and is replication complete? o M phase- consists of Mitosis (cell division and nuclear division), spindle assembly checkpoint and cytokinesis  The differences between Meiosis and Mitosis: o Meiosis I- (Prophase I) chromosomes condense, dyads are visible and there is crossing over between homologous chromosomes (i.e. chromosomes from each parent; there can be recombination)—the breaking down of the nuclear membrane and the condensing of the chromosomes  Chiasmata- the mixing of material and they can create recombinant chromosomes—located on the tetrad, which is created when two sister chromatids are lined up (i.e. homologous chromosomes are lined up)  Metaphase I- homologous pairs line up along the metaphase plate and chromosomes are randomly distributed in Metaphase I—this is random assortment (results in increased genetic variation) and it means that the portions of the chromosome that cross over or exchanged and how they are placed are completely random.  Anaphase I- homologous pairs separate and move toward opposite poles, but sister chromatids remain attached at the centromere.  Telophase I- chromosomes arrive at opposite poles, the nuclear membrane reforms and cytokinesis follows. o Meiosis II- the second meiotic division is analogous to a mitotic division in that there is no reduction of genetic information—however, because of recombination and random assortment, the products of meiosis II are not genetically identical cells and they vary compared to their parent cells.  Prophase II- the chromosomes are condensed  Metaphase II- individual chromosomes line up at the equatorial plate  Anaphase II- Sister chromatids separate and move toward opposite poles  Telophase II- chromosomes arrive at the opposite poles and the cytoplasm divides.  Places to add genetic variation- Prophase I of Meiosis I with recombination and during Metaphase I with random assortment. o Recombination is a strong enough reason for the fact that you and your siblings will not exactly look alike (nearly impossible).  Sex chromosomes are not homologous, but pair up as if they are homologous because of Psuedoautosomal regions (regions at the tip of the sister chromatids). Terms that were not discussed in class: o Leptotene- the first stage of prophase of meiosis, during which each chromosome becomes visible as two chromatids o Tubulin- a protein that is the major building block of microtubules o Centrosome- an organelle near the nucleus of a cell that contains the centrioles (in animal cells) and from which the spindle fibers develop in cell division o Bivalent/ tetrad- (bivalent) a set of homologous chromosomes; (tetrad) a group of four chromosomes or two sets of sister chromatids o Zygotene-the second stage of the prophase of meiosis, following Leptotene, during which homologous chromosomes begin to pair o Pachytene- the third stage of the prophase of meiosis, following Zygotene, during which the paired chromosomes shorten and thicken, the two chromatids of each separate, and exchange of segments between chromatids may occur. o Diplotene- the fourth stage of the prophase of meiosis, following Pachytene, during which the paired chromosomes begin to separate into two pairs of chromatids

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Diakinesis- the final stage of the prophase of meiosis, following Diplotene, when the separation of homologous chromosomes is complete and crossing over has occurred. Synaptonemal complex- a protein structure that forms between homologous chromosomes (two pairs of sister chromatids) during meiosis and is thought to mediate chromosome pairing, synapsis and recombination Chiasmata- (singular = Chiasma) a point at which pair chromosomes remain in contact during the first metaphase of meiosis, and at which crossing over and exchange of genetic material occur between the strands Synapsis- the pairing of two homologous chromosomes that occurs during meiosis; it allows the matching-up of homologous pairs prior to their segregation, and possible chromosomal crossover between them—takes place during prophase I of meiosis Cohesin- the protein complex that regulates the separation of sister chromatids during cell division, either mitosis or meiosis. Shugoshin- a protein that connects to the kinetochore and guides cohesion to prevent premature separation of the sister chromatids.

NOTE: ALL OF OUR CELLS HAVE 46 CHROMOSOMES; OUR SEX CHROMOSOMES HAVE 23!  (CH. THREE) Mendelian Genetics- (Gregor Mendel) a monk in the 14th or 16th hundreds in France who studied pea plants and their reproduction—he described the basic or simplest version of that type of inheritance, but the principles he laid out holds true regardless of how the inheritance displays itself. o Mendel looked at seed color (yellow or green), seed shape (wrinkled or round) and seed coat color (gray or white). o His work allows us to make predictions. o Mendel’s Method- used pure-breeding plants (homozygous for a trait), removed anthers from one plant before maturation, took pollen from another plant and manually fertilized the anther-less plant and began with plants that differed in only one character, a Monohybrid cross.  Monohybrid cross- a controlled cross that tracks one trait.  Mendel’s Results- used pure-bred in P generation and crossed them  F1 generation only had round seed  F2 generation there was a 3:1 ratio of round to wrinkled—This means that there must be the production of two factors  The principle of segregation- the two alleles in each plant separate and each gamete only gets one and the two alleles of a plant separate with equal probability

When placed onto meiosis- every diploid organism has two alleles for any particular characteristic—these alleles separate when gametes form and they separate in equal proportion (one allele per gamete)  The concept of dominance- the way two alleles at one locus interact to produce a phenotype o Mendel was describing something called complete dominance— complete dominance- the trait that remained unchanged in F1 = dominant; the trait that disappears in F1= recessive.  Genetic Terminology to keep in Mind: o Gene- an inherited factor that determines a characteristic o Alleles- different variations of a gene (i.e. round or wrinkled seed) o Locus- (the plural is loci) the place on a chromosome an allele is found. o Genotype- the set of allele an organism has (i.e. RR or rr) o Homozygous (homozygote)- a diploid organism with two identical alleles at a given locus o Heterozygous (heterozygote)- a diploid organism with two different alleles at a given locus. o Phenotype- manifestation or appearance of a characteristic (i.e. round or wrinkled) NOTE: Different alleles of a particular gene occupy the same locus on homologous chromosomes! o Example of an Allele- Sickle Cell Anemia is caused by the Hemoglobin Beta gene (HBB) on chromosome 11; the adult hemoglobin allele is (HbA) and some will carry the Sickle Cell allele (HbS)  Punnett Square- taking the genotype for one parent and place it on one axis in separate boxes (one for each allele) and then do the same for the other parent on a separate axis o Test Cross- used to determine the genotype of an organism displaying a dominant phenotype— cross an organism with a known homozygous recessive.  (Ex.) A tall pea plant’s genotype is either TT or Tt and to determine which genotype, it is crossed with a homozygous recessive plant (tt)—if all progeny are tall, then the genotype is TT; if some are short, it is Tt. o Probability in Genetics- (the multiplication rule) the probability of two or more independent events occurring together is calculated by multiplying their independent probabilities—i.e. the probability of rolling a four and then another four is (1/6) x (1/6) = 1/36.  The addition rule- the probability of any one of two or more mutually exclusive events is calculated by adding the probabilities of these events—i.e. the probability of rolling a four or a three is 1/6 +1/6 = 1/3  Dihybrid crosses reveal the Principle of Independent Assortment o The Principle of Independent Assortment- when these two alleles separate, their separation is independent of the separation of other alleles at other loci—this principle is an extension of the Principle of Segregation o Mendel’s Question- Do alleles encoding different traits separate independently—Results: he found that the allele encoding color separated independently of the allele encoding seed shape producing a 9:3:3:1 ratio in the F2 progeny.  Branch Diagram Method- considering a testcross between a round, yellow plant and a green, wrinkled plant, we will first break the cross down into two monohybrid crosses (i.e. considering round or wrinkled and then yellow or green), where you get half round and half wrinkled, but also half yellow and half green. o Then, we combine the monohybrid crosses by multiplication (in this case). LECTURE TWO:  Review from last lecture: o Eukaryotes- (animal cells) composed of DNA that is within the nucleus—there is a controlled membrane that most of the material going into and out of the nuclear membrane move via energy o Human Genome- (generalize to all eukaryotes) have 46 chromosomes and are diploid (2N)—they have 22 autosomal pairs of chromosomes and 1 pair of sex chromosomes  REMEMBER THAT DIFFERENT ORGANISMS HAVE DIFFERENT NUMBERS OF CHROMOSOMES!!!  The sperm and the egg are considered to be haploid (1N or N)  The gametes create sperm or egg through meiosis, whereas somatic cells undergo mitosis o Chromosome structure- we orient ourselves to the relationship with the centromere, whereas the short arm is the p-arm and the long arm is the q-arm  Kinetochore- the place of spindle fiber attachment o

Cell Life Cycle- (interphase) when the chromosome is unreplicated, (s phase) when the chromosomes undergo DNA replication or synthesis, (m phase) when the chromosome undergoes mitosis or cell division.  This is cell division whereas apoptosis, cell programmed death, is the opposite process.  The checkpoints are important to check for DNA damage to prevent mutations and cancer. o Mitosis- the goal is to create identical cells at the end of the process—meaning, it will start off with 46 chromosomes and duplicate those chromosomes. o Meiosis- analogous to mitosis for most of it (meiosis II same as mitosis)—so, in meiosis I there is a reductional division (4623) and then in meiosis II, there is an equational division (23  46)  The Chiasmata in meiosis I is the actual crossing over of the homologous pairs (rather than the product)  Reductional division- if there are two homologous chromosomes within one cell, there will be the result of 1 sister chromatid per cell (2 cells) after Meiosis I  Equational division- you will begin with a sister chromatid per cell and then end with individual chromosomes in Meiosis II  Difference between Metaphase and Metaphase II- if you begin with 4 chromosomes, in Metaphase you will still have 4 chromosomes at the metaphasal plate whereas in Metaphase II, you will have two chromosomes per cell, which the cells have not completely divided yet. (CH. FIVE) Extensions on Mendel- involved lethal alleles, concept of dominance, gene interactions (i.e. epistasis), CFTR, penetrance and expressivity, sex-influenced, sex-linked, sex-limited, genomic printing and environmental contributions. o Example of Mendel’s Work that Provided Complications- they took two mice (one gray, one white) and all of the F1 generation was gray; the F2 generation…  Another example- when taking two yellow mice and breeding them, they would end up a 2:1 ratio of yellow and some other color, finding that the gene for the yellow coat color is lethal—lethal alleles- cause death usually early in development, can alter phenotypic ratios and can be dominant or recessive. o Concept of dominance- includes codominance and incomplete dominance  Dominant- heterozygote is the same as one parent  Incomplete dominance- heterozygote is intermediate—the heterozygote falls between the homozygotes  Example- when breeding a white and red plant, the heterozygote phenotype could be some light or dark form of a pink.  Example of eggplant- crossing a purple (dominant allele) and white eggplant (does not add pigment) results in violet eggplant—you can think of it as the capital P or the dominant allele is giving too much pigmentation.  The phenotypic ratio will match the genotypic ratio.  Codominance- the heterozygote exhibits both phenotypes, meaning the heterozygote has the phenotype of both parents (i.e. blood)  In contrast with incomplete dominance  Example of Blood Type- there are three different alleles that determine your blood type: IA, IB and i [possible: (IA IA), (IA i), (IB IB), (IB i), (IA IB), (ii)—AB is the universal recipient because it has both antigens A and B and O is the universal donor because it have neither the antigen A nor B o Gene Interactions- refers to how genes at one locus interact with genes at another locus to create your phenotype  Example of Bombay phenotype- recessive epistasis—epistasis- there is a epistatic gene (the one that does the masking) and a hypostatic gene (the gene whose effect is masked).  Individuals with Bombay phenotype are hh and are not allowed to convert the intermediate to Compound H—they will have blood type O because it may not be able to produce Compound H or it just does not have to provide an antigen because of the lack of the compound H.  The H locus interacts with the AB locus to determine blood type  Example of Cystic Fibrosis- cystic fibrosis is a recessive, genetic disease and is common amongst groups that tend to intermingle amongst themselves (i.e. Ashkenazi Jews, Native Americans) and more than 10 million Americans are unknowing, symptomless carriers  The median age of surviva...