Bio2b Midterm 1 PDF

​ Mitosis (IPMAT) ○​ Cellular replication without chromosomal reduction ○​ One parent cell, it does mitosis, you get 2 daughter cells ○​ If you started at diploid, you end up with diploid ○​ How you make more cells, you become multicellular… ○​ How you repair thing...

​ Mitosis (IPMAT) ○​ Cellular replication without chromosomal reduction ○​ One parent cell, it does mitosis, you get 2 daughter cells ○​ If you started at diploid, you end up with diploid ○​ How you make more cells, you become multicellular… ○​ How you repair things ​ IPMAT ○​ Interphase: ​ The cell prepares for division by replicating its DNA and growing in size. ○​ Prophase: ​ Chromosomes become visible, the nuclear membrane breaks down, and spindle fibers start to form ○​ Metaphase: ​ Chromosomes line up along the equator of the cell, attaching to the spindle fibers ○​ Anaphase: ​ Sister chromatids of each chromosomes are pulled apart and move toward opposite poles of the cell. ○​ Telophase; ​ New nuclear membranes form around the separated chromosomes, essentially creating two new nuclei. ​ REASSEMBLE THE NUCLEAR ENVELOPE ​ You do cytokinesis= splitting into the daughter cells ​ You do not need to do cytokinesis, if you do mitosis ​ Meiosis ○​ Cellular replication with chromosomal reduction ○​ One parent cell to 4 daughter cells ○​ Diploid to haploid ○​ PMAT ​ Prophase:  ​ The first stage of meiosis ​ Prophase 1: you dissemble nuclear envelope, assemble the mitotic spindle, condense the chromosomes ○​ The homologous pairs come together = the tetrad ​ You have 4 copies of the genes for that chromosomes, you can do crossing over and recombination (the 2 in the middle) ​ Metaphase: ​ Chromosomes line up in the middle of the cell ​ Metaphase 1: what’s aligned on the metaphase plate is the tetrad, which are the homologous pairs = when the kinetochore of the centromere is attached to a mitotic spindle and you segregate at anaphase one, you segregate homologous pairs. = 2 cells (one cell is haploid double stranded, other cell is haploid double stranded) ​ Metaphase 2: sister chromatids, segregate sister chromatids,= 4 cells (haploid single stranded x 4) ​ Anaphase: ​ Sister chromatids are pulled apart ​ Telophase: ​ Nuclear membranes reform around each set of chromosomes ____________________________________________________________________________ Achieve- Week 1 Notes ​ Substitution of one nucleotide for a different nucleotide ○​ Most common type of mutation (rare) ○​ Rate of occurrence differs among organisms. ​ HotSpots: ○​ A site in the genome that is very mutable. ○​ Often in sites in the DNA which cytosine bases are chemically modified for purposes of gene regulation. ​ Germ Cells (haploid gametes and the diploid cells that give rise to them: ○​ A reproductive cell that produces gametes (sperm or eggs) ○​ Germ-line Mutations: a mutation that occurs in eggs and sperm or in the cells that give rise to these reproductive cells and therefore is passed on to the next generation. (researchers are most interested in the number of mutations per genome per generation). ○​ Germ-like mutations are important to the evolutionary process because they are passed from one generation to the next. ​ Somatic Cells (the other cells of the body): ○​ A nonreproductive cell, the most common type of cell in the body of a multicellular organism. ○​ Somatic Mutations: a mutation that occurs in somatic cells  ○​ Somatic mutations’ what matters: the rate of mutations per nucleotide per replication. ○​ Somatic mutations ARE NOT transmitted to future generations; they are transmitted to daughter cells in mitotic cell divisions. ○​ Somatic cells affect the cell in which it occurs and all the cells that descend from it. ○​ Most cancers result from mutations in somatic cells. ​ Germ Cells VS. Somatic Cells: ○​ The rate in Somatic Cells is almost 100 times greater than germ cells. ○​ Germ cells- mutations are transmitted to the next and future generations, whereas Somatic-cells mutations are not. ​ In mammals: ○​ The rate of mutation per nucleotide per replication is greater in somatic cells than in germ cells because DNA repair mechanisms are more efficient in germ cells. ​ Germ-Line Mutations ○​ Mutations that occur in germ cells ○​ Researchers interested in the number of mutations per genome per generation. ○​ Important to evolutionary process because they are passed from one generation to the next, they may eventually come to be present in many individuals descended from the original carrier. ​ Somatic Mutations: ○​ Mutations that occur in somatic cells ○​ What matters: the rate of mutations per nucleotide per replication. ○​ Transmitted to daughter cells in mitotic cell divisions. ○​ Somatic mutations affect the cell in which mutation occurs and the cells that descend from it. ​ Example: Japanese morning glory flower: lineage ability to make purple pigment cause sectors of different pigmentation in the flower. ○​ Most cancers. ​ Several Mutations must occur sequentially in a single cell lineage for the disease to manifest. ​ Example: Colon cancer: Mutation in APC gene, Mutation in Ras gene, Mutation in p53 gene ○​ Mutations increases/decreases the activity of a gene that promotes cell division ​ Two Hypothesis: ○​ 1: Suggests that mutations occur with regard to the needs of an organism. (Ex: the presence of the antibiotic in the experiment with bacterial cells ○​ 2: Suggests that some sort of feedback occurs between the needs of an organism and the process of mutations, such that the environment directs specific mutations that are beneficial to the organism. ​ Hypothesis test: ○​ Replica Plating. Chapter 14.1 Meiotic Cell Division ​ Gametes: egg and sperm ○​ Gametes produced by cell division: Meiotic Cell Division ​ Meiotic: ○​ 1. Results in 4 daughter cells instead of 2. ○​ 2. Each of the 4 daughter cells produced by meiotic cell division contains half the number of chromosomes as the parent cell instead of the same number. ○​ 3. Each of the 4 daughter cells produced by meiotic cell division is genetically unique instead of genetically identical. ○​ 1 round of DNA replication ○​ 2 cell divisions ​ Meiosis I: reductional division; the first stage of meiotic cell division, in which the number of chromosomes is halved from 2n to n.  ​ Meiosis II: equational division; second stage of meiotic cell division, the number of chromosomes is unchanged. ​ Sister chromatids separate, as in mitosis. ○​Meiosis I: ​Begins with Prophase I ​ The condensing chromosomes first become visible, ​ Chromosomes appear as long, thin threads present throughout the nucleus. ​ Each chromosome has become 2 sister chromatids held together at the centromere. ​ Homologous chromosomes pair with each other (maternal and paternal pairs of chromosomes are called homologous chromosomes. ​ Homologous chromosomes match in size and appearance ○​ Have the same genes arranged in the same order along their length. ○​ Each homologous chromosome is a pair of sister chromatids attached to a single centromere, a pair of synapse chromosomes creates a 4-stranded structure: two pairs of sister chromatids aligned along their length. = Bivalent ○​ The chromatids attached to different centromeres are called nonsister chromatids. Results from the replication of homologous chromosomes (one is maternal, other is paternal in origin) = same set of genes in the same order, but not genetically identical. ○​ Sister chromatids results from replication of a single chromosome are genetically identical. Crossing Over Between DNA Molecule Results in Exchange of Genetic Material ​ Chiasma: a crosslike structure within a bivalent (paired homologous chromosomes) constituting a physical manifestation of crossing over. ○​ Chiasma results when nonsister chromatids break and then join where maternal and paternal genetic material is exchanged. ○​ No nucleotides are gained or lost as homologous chromosomes exchange material. Is random. ○​ Crossing over increases genetic diversity. ○​ Number of chiasmata form during meiosis depends on the species. ○​ Chiasmata also hold the bivalent together while they become properly oriented in the center of the cell during metaphase. ​ Quick Prophase I summary: ○​ At the end, the chromosomes are fully condensed and have formed chiasmata. ○​ The nuclear envelope has begun to disappear  ○​ The meiotic spindle is forming ​Prometaphase I ○​ The nuclear envelope breaks down and the meiotic spindles attach to kinetochores on chromosomes. ​Metaphase I: ○​ The bivalents move until they end up on an imaginary plane cutting transversely across the spindle. ○​ Each bivalent line so that its two centromeres lie on opposite sides of the plane, pointing toward opposite poles of the cell. ○​ The random alignment increases genetic diversity in the products of meiosis. ​Anaphase I: ○​ The two homologous chromosomes of each bivalent separate as they are pulled in opposite directions, but the sister chromatids remain joined at the centromere. ○​ Key feature: the centromeres do not split and the two chromatids that make up each chromosome remain together. ○​ Chromatids remain together because spindle microtubules from one pole of the cell attach to both kinetochores of a given chromosome during prometaphase I. ○​ Only one of the 2 homologous chromosomes goes to each pole, in humans there are 23 chromosomes ○​ Each chromosome consists of 2 chromatids attached to a single centromere. ​Telophase I: ○​ The chromosomes decondense slightly ○​ A nuclear envelope briefly reappears ○​ The process of cytokinesis divides the cytoplasm, producing 2 separate cells. Meiosis II ​Prophase II: ○​ The nuclei have the haploid number of chromosomes, not the diploid number ○​ Chromosomes recondense to their maximum extent. ○​ The nuclear envelope begins to disappear ○​ Spindle begins to be set up ​Prometaphase II: ○​ Spindles attach to kinetochores ​Metaphase II: ○​ The chromosomes line up so that their centromeres lie on an imaginary plane cutting across the spindle ​Anaphase II: ○​ The centromere of each chromosome splits. ○​ The separated chromatids, now each regarded as a full-fledged chromosome, are pulled toward opposite poles of the spindle. ​Telophase II: ○​ The chromosomes uncoil and become decondensed ○​ A nuclear envelope re-forms around each set of chromosomes. ○​ The nucleus of each cell has the haploid number of chromosomes. ○​ Equational division. Division of the cytoplasm often differs between the sexes ​ In multicellular organisms, the division of the cytoplasm in meiotic cell division differs between the sexes. ​ In females: division is unequal in both meiotic divisions ○​ Polar bodies: a small cell produced by the asymmetric first meiotic division of a primary oocyte. ​ In males: division is equal in both meiotic divisions. ○​ Each division results in meiotic products going to form functional sperm. ​ Chromosome theory of Inheritance: states that chromosomes are the basis for inheritance as they are passed from parent cell to daughter cell during cell division. Nondisjunction ​ Nondisjunction: is the failure of a pair of chromosomes to separate normally during anaphase of cell division. ○​ One daughter cell receives an extra copy of one chromosome. ○​ One daughter cell receives no copy of that chromosome. ○​ In Mitosis: ​ Leads to cell lineages with extra or missing chromosomes. ​ Result is gametes that have either an extra or missing chromosome. ​ In first division nondisjunction: ○​ Failure of homologous chromosome separation in meiosis I. ○​ All the resulting gametes have an extra or missing chromosome. ​ In second division nondisjunction: ○​ Sister chromatids fail to separate, giving rise to gametes with an extra chromosome, a missing chromosome, or proper numbers of chromosomes. Genotype and Phenotype ​ Genotype: the genetic makeup of a cell or organism. ​ Homozygous: two copies of the same allele ​ Heterozygous: an individual with two different alleles of a gene. ​ Phenotype: the individual’s observable characteristics or traits. ○​ Examples: color blindness, lactose intolerance, development, physiology, or behavior of a cell or organism. ○​ Results in part from the genotype. ​ Example: a genotype with a mutation that affects expression of an enzyme that breaks down the sugar lactose can lead to the phenotype of lactose intolerance. ○​ A phenotype results from an interaction between the genotype and the environment. ​ Harmful Mutations ○​ Often eliminated in one or a few generations because they decrease the survival or reproduction of the individuals that carry them. ○​ Exemplified by alleles of the gene HTT, which encodes the protein HTT, or huntingtin. ​ Neutral Mutations ○​ A mutation that does not affect survival or reproduction ○​ Occur mostly in noncoding DNA ○​ Likely to occur in organisms with large genomes and abundant noncoding DNA ○​ Can also occur in protein-coding regions of DNA. ​ Example: gene TAS2R38, encodes a taste receptor in the tongue= some individuals perceive a bitter taste from certain chemicals. ​ Beneficial Mutations ○​ Improves the chance of survival and reproduction. ​ Example: 35% of people can digest milk. Milk is a nutritious food resource. (calcium, bone density) ​ Effect of a Mutation may depend on the genotype and environment ○​ Effects of a mutation may be strengthened, weakened, or reversed depending on the presence of other mutations in different genes in the same genome. ○​ The effect of a mutation often depends on whether the mutation is homozygous or heterozygous. ​ Example: in areas with malaria, the S allele is harmful as a homozygous genotype, but is beneficial as a heterozygous genotype. ○​ Effect of a mutation may depend on the environment ​ Example: the S allele, when heterozygous, is beneficial only in malarial-prone regions, where it offers protection from the disease that outweighs its other effects. In areas without malaria, it is harmful. Mendel’s experimental organism was the garden pea ​ Hybridization: the interbreeding between two different varieties or species of an organism. ​ Mendel studied seven physical features expressed in contrasting fashion among the strains: seed color, seed shape, pod color, pod shape, flower color, flower position, and plant height. ​ True Breeding: a trait whose physical appearance in each successive generation is identical to that in the previous one. ○​ Example: plants of the strain with yellow seeds produced only yellow seeds; those of the strain with green seeds produced only green seeds. ​ Objective of experiment: ○​ By means of crosses between the true-breeding strains and crosses among their progeny, Mendel hoped to determine whether statistical patterns could be seen on the occurrence of the contrasting characteristics, such as yellow seeds or green seeds. In crosses, one of the traits was dominant in the offspring ​ ​ ​ ​ P1 generation: the parental generation in a series of crosses ​ F1 generation: the first filial, or offspring, generation of a particular mating. ○​ Example: in the cross of P1 yellow x P1 green, all of the F1 progeny had yellow seeds. ​ Reciprocal Crosses: a cross in which the female and male parents are interchanged. ○​ Mendel showed that reciprocal crosses yielded the same result for each of his seven pairs of contrasting traits.  ○​ Each pair of contrasting traits, only one of the traits appeared in the F1 generation. ○​ Dominant: describes an allele or trait that is expressed in heterozygotes; only one one dominant allele is needed to express the phenotype. ○​ Recessive: describes an allele or trait that is only expressed in homozygous; two recessive alleles are needed to express the phenotype. Segregation ​ F1 progeny of a cross between plants with different traits did not breed true. ​ In F2 generation: the second filial generation; the offspring from intercrossing among F1 individuals. ​ Genes come in pairs that segregate in the formation of reproductive cells. Explanation of the 3 : 1 ratio in the F2 1.​ Except for cells involved in reproduction, each cell of a plea plant contains two alleles of each gene. In each true-breeding strain constituting the P1 generation, the two alleles are identical. a.​ The AA and aa genotypes are homozygous, both alleles inherited from the parents are the same. 2.​ Each reproductive cell, or gamete contains only one allele of each gene. A gamete can contain the A allele or the a allele, but not both. 3.​ In the formation of gametes, the two members of a gene pair segregate (or separate) equally into gametes, so half the gametes get one allele and half get the other allele  a.​ This separation of alleles into different gametes define the principle of segregation. b.​ In the case of homozygous plants (such as AA or aa), all the gametes from an individual are the same. = homozygous AA strain with yellow seeds produces gametes containing the A allele, and the homozygous aa strain with green seeds produces gametes containing the a allele. 4.​ The fertilized egg cell, called the zygote, is formed from the random union of two gametes, one from each parent. a.​ For the cross AA x aa, the zygote is an F1 hybrid formed from the union of an A-bearing gamete with an a-bearing gamete. b.​ Each F1 hybrid has genotype Aa i.​ The Aa genotype is heterozygous, the two alleles for a given gene inherited from each parent are different. 5.​ When the F1 progeny (genotype Aa) form gametes, by the principle of segregation the A and a alleles again separate equally so that half the gametes contain only the A allele and the other half contain only the a allele. 6.​ In the formation of the F2 generation, the gametes from the F1 parents again combine at random. The consequences of the random union of gametes can be worked out by means of a Punnett Square. 7.​ The boxes of the Punnett square correspond to all of the possible offspring genotypes of the F2 generation, with each possible genotype’s frequency obtained by multiplying the gametic frequencies in the corresponding row and column. Principle of segregation was tested by predicting the outcome of crosses ​ The Punnett Square makes 2 predictions:​ ○​ 1. Predicts that the seeds in the F2 generation showing the recessive green seed phenotype should be homozygous aa, in which case they should breed true. ○​ 2. Predicts the seeds in the F2 generation that show the dominant yellow phenotype. ​ Although these seeds have the same phenotype, they have two different genotypes (AA and Aa). ​ Plants with the AA and Aa genotypes can be distinguished by the types of seeds they produced when self-fertilized. ​ The AA plants produce only seeds with the dominant yellow phenotype (they are true breeding) ​ The Aa plants yield dominant yellow and recessive green seeds in the ratio 3 : 1. A testcross is a mating to an individual with the homozygous recessive genotype ​ More direct test of segregation is to cross the F1 progeny with the true-breeding recessive strain instead of allowing the to self-fertilize. ​ Testcross: any cross of an unknown genotype with a homozygous recessive genotype. Segregation of alleles reflects the separation of chromosomes in meiosis  ​ Dominance is not universally observed ​ Most traits are determined by multiple genes or the interaction of genotype and the environment ​ Incomplete dominance: inheritance in which the phenotype of the heterozygous genotype is intermediate between those of homozygous genotypes. ​ Codominance : the expression of both alleles in a genotype heterozygous for two alleles, with neither allele being recessive or dominant to the other. ○​ Example: ABO blood groups. The letters A and B refer to modified carbohydrates found on the surface of red blood cells. The principles of transmission genetics are statistical and are stated in terms of probabilities ​ Probability: among a very large number of observations, the expected proportion of observations that are of a specific type. ​ The probability of occurrence of a genotype must always lie between 0 and 1 ○​ Probability of 0= the genotype cannot occur ○​ Probability of 1 = the occurrence of the genotype is certain. ​ Example: in the cross of Aa x AA, no offspring can have the genotype aa ​ In Mating AA x aa, all offspring must have the genotype Aa. ​ Aa x Aa is ¼  ​ Aa x aa is ½ ​ Addition rule: ○​ This principle applies when the possible outcomes being considered cannot occur simultaneously. ​ For example: a single offspring is chosen at random from the progeny of the mating Aa x Aa, and we wish to know the probability that the offspring is either AA or Aa. ​ Key words: “either” and “or” ​ In this example, the chosen offspring could have either genotype AA (with probability ¼) or genotype Aa (with probability ½) ○​ The probability that the chosen individual has either AA or Aa genotype is given by ¼ + ½ = ¾. ​ Multiplication Rule ○​ The principle that the probability of two independent events occurring together is the product of their respective probability. ○​ Events that do not influence one another are independent. ○​ This rule is used to determine the probabilities of successive offspring of a cross because each vent of fertilization is independent of any other. ​ For example: the mating Aa x Aa, determine the probability that, among four peas in a pod, the one nearest the stem is green and the other yellow. ​ Keyword: “and” ​ ¼ x ¾ x ¾ x ¾ = 27/256 Nearby Genes in the Same Chromosome Show Linkage ​ Linked Genes: describes genes that are sufficiently close together in the same chromosome that they do not assort independently. ○​ Two genes that are close together in the same chromosome ​ May be an autosome or sex chromosome. ​ The phenotypes of the male offspring of a female reveal the female's genotype for X-linked genes. ​ Each male progeny receives its X chromosome from the mother and its Y chromosome from the father. ​ Each female receives the X chromosome from her father. ​ The lack of independent assortment means that the genes show linkage. ​ Nonrecombinants: progeny in which the alleles are present in the same combination as that present in a parent. ​ Recombinants: an offspring with a different combination of alleles from that of either parent, resulting from one or more crossovers in prophase I of meiosis.  ​ Crossing over is a key process in meiosis. ○​ Occurs at the 4-strand stage of meiosis (when each homologous chromosome is a pair of sister chromatids. ○​ Only two of the 4 strands (one sister chromatid from each homologous chromosome) are included in any crossover. ○​ Females average about 2.75 crossovers per chromosome pair ○​ Males average about 2.50 crossovers per chromosome pair. The Frequency of Recombination is a Measure of the Genetic Distance Between Linked Genes ​ When two genes are on separate chromosomes, a ratio of 1:1:1:1 is expected for the nonrecombinant (nonparental) gametic types = independent assortment. ​ When genes are very far apart from each other = one or more crossovers will likely occur between them. ○​ 1:1 ratio of nonrecombinant to recombinant gametes. ​ When genes are so close together that crossing over never takes place between them ○​ Only expect nonrecombinant chromosomes. ​ Frequency of Recombination: is a measure of genetic distance between the genes along the chromosome. ○​ 0% = when genes are so close together that crossing over never takes place ○​ 50% = genes are so far apart that crossover between genes almost always takes place. ○​ Maximum frequency is 50%. ○​ A frequency of recombination of 50% yields the same ratio of gametic types as observed with independent assortment. ​ In studies of genetic linkage, the distance between genes is measured by the frequency of recombination. Genetic Mapping Assigns a Location to Each Gene Along a Chromosome ​ Genetic Map: a diagram showing the relative positions of genes along a chromosome. ​ Map Unit: A unit of distance in a genetic map equal to the distance between genes resulting in 1% recombination. ​ Genetic maps are built up step by step as new genes are discovered that are genetically linked. ​ Across distances that are less than 15 map units, the map distances are approximately additive, which means that the distance between adjacent genes can be added to get the distance between the genes at the ends.  ​ The recombination frequency between w (white eyes) and cv (crossveinless) was calculated as 4.0 + 2.0 + 6.2 = 12.2%, but the 1.5 map units between y (yellow body) and w were not included. This is because the calculation only considers the distances between w and cv, starting at w. ​ Map units (centimorgans) are additive over short distances, but only the segments between the two genes of interest are summed. If we were calculating recombination between y and cv, then the 1.5 map units would be included, making the total 13.7% instead. ​ This principle helps in genetic mapping by ensuring that only relevant gene distances are used when predicting recombination frequencies. Independent Assortment is Observed when Genes Segregate Independently of One Another ​ Principle of Independent Assortment: states that segregation of one set of alleles of a gene pair is independent of the segregation of another set of alleles of a different gene pair. ○​ Each pair of alleles assorts (segregates into games without affecting or being affected by the assortment of any other pair of alleles. Dominant Traits Appear in Every Generation ​ If a dominant trait is rare, then affected individuals will almost always be heterozygous (Aa), not homozygous (AA) ​ In a mating in which one parent is heterozygous for the dominant gene (Aa) and the other is homozygous recessive (aa); half of the offspring are expected to be heterozygous (Aa) and the other half homozygous recessive (aa). Recessive Traits Skip Generations ​ For an individual to be affected, that person must inherit the recessive allele from both parents. ​ The recessive allele in the common ancestor can be transmitted to both parents, making them each a carrier of the allele as well. ​ If both parents are unaffected carriers of the allele, they both have the genotype Aa, and ¼ of their offspring are expected to be homozygous aa and affected. Week 3 Point Mutations are Changes in a Single Nucleotide ​ Point Mutations: a mutation in which a base pair is replaced by a different base pair; this is the most frequent type of mutation.  ​ Single-nucleotide polymorphism: a site in the genome where the base pair that is present differs among individuals in a population. (SNP (pronounced Snip)) ○​ A SNP is the result of a point mutation that occurred sometime in the past and then increased in frequency so that many individuals in the population now carry it. ​ Example: differences among the A, S, and C alleles of the gene for B-globin are SNPs because they differ from one another at just one nucleotide site and are present in modern-day populations. The effect of a point mutation depends in part on where in the genome it occurs ​ In many multicellular eukaryotes, including humans, the vast majority of DNA in the genome does not code for protein or for RNAs with known function ​ Most of the sequences in noncoding DNA have no known function, which may explain why many point mutations in noncoding DNA have no detectable effects on the organism. ​ Point mutations in coding sequences do have predictable consequences in an organism. ​ Synonymous mutations do not change the amino acid sequence of the resulting protein. Nonsynonymous mutations change the amino acid sequence. ​ In the figure, the mutation, an A-T base pair is substituted for the normal G-C base pair. When transcribed into mRNA, the mutation changes the normal GAG codon into the mutant GAA codon. But GAG and GAA both code for the same amino acid, glutamic acid (Glu). ○​ Are synonymous codons, so the resulting amino acid sequence are the same: Pro-Glu-Glu. ​ Synonymous (silent) mutations: a point mutation resulting in a codon that does not alter the corresponding amino acid in the polypeptide.  ○​ Typical in that the synonymous codons differ at their third position (the 3’ end of the codon) ​ Nonsynonymous (missense) mutations: change the amino acid sequence. ​ Amino Acid Replacement: a change in the amino acid at a particular site in a protein resulting from a mutation in a gene. ​ Nonsense Mutation: creates a stop codon that prematurely terminates translation. ○​ Nearly always has harmful effects. Small insertions and deletions involve several nucleotides ​ In noncoding DNA, such mutations have little or no effect. ​ In protein-coding regions, their effects depend on their size. ​ A small deletion or insertion that is an exact multiple of three nucleotides results in a polypeptide with fewer (in the case of a deletion) or more (in the case of an insertion) amino acids as there are codons deleted or inserted. ○​ Example: a deletion of three nucleotides eliminates one amino acid, and an insertion of six nucleotides adds two amino acids. ○​ Example: effects of a deletion of three nucleotides can be seen in cystic fibrosis. Mutations responsible occur in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The CFTR protein is a chloride channel, which acts as a transporter to pump chloride ions out of the cell. Malfunction of CFTR causes ions imbalances that result in abnormal secretions from the many cell types in which the CFTR gene is expressed. ​ Frameshift Mutations: a mutation in which an insertion or deletion of some number of nucleotides that is not a multiple of three causes a shift in the reading frame of the mRNA, changing all following codons. Some mutations are due to the insertion of a transposable element ​ Transportable Element (transposons): A DNA sequence that can replicate and move from one location to another in a DNA molecule; also called a transposable element (TE). ○​ WHen such a large piece of DNA inserts into a gene, it can interfere with transcription, cause errors in RNA processing, or disrupt the open reading frame. Duplications and Deletions Result in gain or Loss of DNA ​ Duplication: a region of a chromosome that is present twice instead of once. ○​ Large duplications are usually harmful and quickly eliminated. ○​ Small duplications of only one or a few genes can be maintained over many generations. ​ Deletion: a region of the chromosome that is missing. ○​ Can result from an error in replication or from the joining of breaks in a chromosome that occur on either side of the deleted region. ○​ Chromosomes usually occur in homologous pairs = deletion may persist in the population. ​ Example: if a homologous pair has a deletion of an essential gene but the gene is present in the other member of the pair, that one copy of the gene is often sufficient for survival and reproduction. ​ Deletions or duplications that include the centromere, the site associated with attachment of the spindle fibers that move the chromosome during cell division are rarely observed,, ​ An abnormal chromosome without a centromere, or one with two centromeres, is usually lost within a few cell divisions because it cannot be directed properly into the daughter cells during cell division. Gene families arise from gene duplication and divergence ​ In most cases, a gene is duplicated, harmless because the other copy continues to carry out the normal function of the gene. ​ Duplication and Divergence: process of creating new genes by duplication followed by change in sequence over evolutionary time. ○​ Divergence refers to the slow accumulation of different mutations in duplicate copies of a gene that occurs on an evolutionary timescale, ​ Gene family: a group of genes with related functions, usually resulting from multiple rounds of duplication and divergence. Copy-Number Variation Constitutes a Significant Proportion of Genetic Variation  ​ Copy-Number Variations (CNVs): differences among individuals in the number of copies of a region of the genome ○​ Regions involved in CNVS are large and may include one or more genes. ​ Some CNVs occur in noncoding regions, but others consists of genes that are present in multiple tandem copies along the chromosome. Tandem Repeats are Useful in DNA Typing ​ Tandem Repeats: a region along a DNA molecule in which many identical copies of a short sequence of nucleotides are adjacent to one another. ​ Each location with a tandem repeat typically has many alleles differing in copy number, so that, except for identical twins, an individual’s genotype at six or eight different locations is usually sufficient to identify the individual uniquely. ​ DNA Typing: the analysis of a small quantity of DNA to uniquely identify and individual (DNA fingerprinting) An Inversion has a chromosomal region reversed in orientation ​ Inversion: the reversal of the normal order of a block of genes ​ An inversion typically produced when the region between two breaks in a chromosome is flipped in orientation before the breaks are repaired. ​ A small inversion may have almost no effect on the organism because it still contains all of the genes present in the original chromosome, merely flipped in their order, and is too small to cause problems in meiosis. ​ A Reciprocal translocation Joins Segments from Nonhomologous Chromosomes ​ Reciprocal Translocation: Interchange of parts between nonhomologous chromosomes. ​ Most reciprocal translocation do not affect the survival of organism because they change only the arrangement of genes and not their number. ​ Gene Dosage: the number of copies of a particular gene present in an individual ○​ Requires the presence of both parts of the reciprocal translocation as well as one copy of each of the normal homologous chromosomes. ○​ Problem can arise in meiosis because both chromosomes involved in the reciprocal translocation may not move together into the same daughter cells, resulting in gametes with only one part of the reciprocal translocation. Complex Traits are Affected by the Environment ​ Quantitative Traits: a complex trait that is influenced by many genes and the environment and that is measurable along a continuum, such as height and weight. ​ Environmental Risk Factor: is a behavior or an aspect of a person’s surroundings that increases the likelihood of developing a particular condition. ○​ Important in agriculture. ○​ Affects the variation in phenotype from one individual to the next. ​ Example: most field of corn you see planted along the roadside come from seeds that are genetically identical to one another, yet phenotypic variation in complex traits determines the height of each cornstalk. ○​ Affect on complex traits in animals: ​ Example: true breeding, homozygous strains such as those used by Mendel in his experiments with pea plants. ​ Inbred Lines: a true-breeding, homozygous strain. Complex Traits are Affected by Multiple Genes ​ The effects of individuals genes are obscured by variation in phenotype that is due to multiple genes affecting the trait and also due to the environment. ​ The number of genes affecting complex traits is usually so large that different genotypes can have very similar phenotypes. ​ The relative frequencies of different shades of red color (seed casing in wheat) could be explained by the effects of three genes that undergo independent assortment. ​ Normal Distribution: a distribution whose plot is a bell-shaped curve. The Relative Effects of Gene and Environment on Traits can be determined by Differences Among Individuals in a Population ​ It is possible to separate genes and environment in regard to their effects on the differences, or variation seen among individuals within a particular population. ​ Some traits, the variation seen among individuals is due to difference in the environment ​ Other traits, the variation is due mainly to genetic differences. Genetic and Environmental Effects can Interact in Unpredictable Ways ​ Norm of Reaction: a graphical depiction of the change in phenotype across a range of environments.  ​ Genotype-by-environment interaction: unequal effects of the environment on different genotypes, resulting in different phenotypes. ○​ Important because it implies the effect of a genotype cannot be specified without knowing the environment, and the other way around. ○​ Example: obesity. ​ For complex traits, phenotype depends on both genotype and environment For Complex Traits, Offspring Resemble Parents but Show Regression Toward the Mean ​ ​ Graph shows the distribution of height among the offspring of the tallest parents in the population Galton studied.  ​ Regression toward the mean: The principle that offspring exhibit an average phenotype that is intermediate between that of the parents and that of the population as a whole. ○​ Example: When the mean height of the parents is smaller than the population mean, the mean height of the offspring is greater than that of the parents (but smaller than the population mean). ○​ When the mean height of the parents is greater than the population, the mean height of the offspring is smaller than that of the parents (but greater than the population mean). ○​ Regression toward the mean is observed for 2 reasons: 1.​ Observed during meiotic cell division, segregation and recombination break up combinations of genes that result in extreme phenotypes, that are present in the parents. 2.​ The phenotype of the parents results not only from genes but also from the environment. Environmental effects are not inherited. Heritability is the Proportion of the Total Variation of a Trait in a Population due to Genetic Differences Among Individuals ​ ​ Blue Line is the regression line expected when all the variation in height results from genetic differences among individuals and when height is determined by a large number of genes, each with small effect and with no dominance or gene interaction. ○​ Under these assumptions, the mean height of the offspring will equal the mena height of the parents, and any deviations from the blue line will be due entirely to chance. ​ The Black Line with a slope of 0.0 represents the opposite extreme, in which all variation in height results from environmental differences among individuals.  ○​ As long as environmental effects are not transmitted from one generation to the next, the mean phenotype of the offspring will be equal to the mean of the population as a whole, irrespective of the phenotype of the parents. ○​ Variation in height among individuals is due to genetic difference and how much is due to environmental difference is shown in the slop of the regression line. (which in Galton’s data equals 0.60). ​ Cultural Transmission: The transfer of information among individuals through learning or imitation. ○​ Example: the average wealth of the offspring of rich parents is greater than that of the offspring of poor parents, and this difference is obviously due to transmission of the parent’s money, not their genes. ​ Heritability: in a population, the proportion of the total variation in a trait that is due to genetic differences among individuals. ○​ In complex trait, the heritability determines how closely the mean of the offspring resembles that of the parents. ○​ Refers to the variation in a trait among individuals, and specifically to the proportion of the variation among individuals in a population due to differences in genotype. ○​ Heritability of 100% means that variation in the environment does not contribute to differences among individuals in a specific population. ​ Example: if genetically different strains of roses are grown in a greenhouse and subject to identical environmental conditions, then differences in flowering time have to be due to genetic differences, and the heritability of the trait would be 100%. ○​ Heritability of 0% means that differences in genotype do not contribute to the variation in the trait among individuals in a specific population. ○​ Heritability applies only to the trait in a particular population across the range of environments that exist at a specific time. ○​ Heritability is important in evolution, particularly in studies of artificial selection, a type of selective breeding in which only certain chosen individuals are allowed to reproduce. ○​ Heritability determines how rapidly a population can be changed by artificial selection. ​ A trait with high heritability responds rapidly to selection, whereas a trait with a low heritability responds slowly or not at all. Complex Traits in Health and Disease Many Genes, Each with a Relatively Small Effect, Contribute to the Most Common Medical Conditions and Birth Anomalies ​ Genome sequencing and genotyping - to identify genes affecting complex traits. ​ Patterns are beginning to emerge. ○​ Patterns can be seen in the chromosome map, which shows the location of genes in the human genome that affect cholesterol levels. ​ Pleiotropy: the phenomenon in which a single gene has multiple effects on seemingly unrelated traits. ​ Observations in a pattern: 1.​ Many genes contribute to amounts of different types of cholesterol in humans 2.​ Many of these genes affect two or even all three types of molecule. 3.​ Many of the genes occur in clusters, being physically close together in the same chromosome. ​ Observation in a 2nd pattern: 1.​ Many of the genes show epistasis. Epistasis occurs when multiple genes act in the same pathway to affect a trait. ​ Observation in a 3rd pattern: 1.​ The effects of each of the genes on cholesterol levels are very unequal. 2.​ Most genes that contribute to a complex trait, the magnitude of their individual effects is typically quite small. a.​ The magnitude of the effects of individual genes also often differs between the sexes, which helps explain why complex traits so often differ in prevalence or severity between males and females. Human Height is Affected By Hundreds of Genes ​ Analysis identified 697 genes affecting height. ​ Some genes affect skeletal development, growth hormones, or other growth factors, but has no obvious connection to the biology of growth. ​ A few genes affecting height are also known to be associated with bone mineral density, obesity, and rheumatoid arthritis. ​ Analysis addresses neither the effects of the environment on human height nor genotype-by-environment interactions. Personalized Medicine Can Lead to More Effective Treatments ​ Different people can have the same medical condition for different reasons. ○​ One person might develop breast cancer because of a mutation in the BRCA1 or BRCA2 gene, whereas another might develop breast cancer because of other genetic risk factors or even environmental ones. ○​ Other examples: cholesterol levels, high blood pressure, and depression ​ Because the underlying genetic basis for the same medical condition may be different in different patients, some patients respond well to certain drugs and others do not. ‘ ​ Personalized Medicine: An approach in which treatment is matched to the patient, not the disease. Examination of an individual’s genome sequence, by revealing his or her disease susceptibilities and drug sensitivities, allows treatments to be tailored to that individual.