GEN 3022 1st Edition Lecture 38Outline of Last Lecture I. Genetic basis of cancera. Characteristicsb. StatisticsII. Viruses that cause cancera. Efficiency of causing cancerb. Acutely transforming virusesc. Rous sarcoma virusIII. Oncogenesa. Development b. Patterns of expressionc. Conversion of proto-oncogenesi. Missense mutationii. Gene amplificationiii. Chromosomal locationsiv. Viral integrationIV. Tumor-suppressor genesa. Inactivation of tumor-suppressor genesi. Mutation in gene itselfii. DNA methylationiii. Aneuploidyb. Genome maintenancei. Checkpoint proteinsii. Cyclins and cyclin-dependent kinasesiii. DNA repair enzymesc. p53 genei. Functionsii. Apoptosisd. Retinoblastomai. Two typesii. Two-hit modelV. Multiple genetic changesa. Development pattern of cancersThese notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.b. Colorectal cancer studyc. Genetic changes leading to cancerVI. Inherited forms of cancersa. Predisposition for developing cancerb. Loss of heterozygosityOutline of Current LectureI. Population geneticsa. Composition of population geneticsb. Gene poolII. Populationsa. Characteristicsb. DemesIII. Allele and gene frequenciesa. Polymorphism b. Single-nucleotide polymorphismc. Allele frequencyi. Equationii. Exampled. Genotype frequencyi. Equationii. Examplee. Trends in frequenciesf. Hardy-Weinberg equilibriumi. Conditionsii. Equationiii. Exampleg. X2 testi. Equationii. Exampleiii. ResultsIV. Patterns of evolutiona. Microevolutionb. Natural selectionc. Genetic drifi. Bottleneck effectii. Founder effectd. Migratione. Non-random matingi. Assortative matingii. Positive assortative matingiii. Negative assortative matingiv. Inbreeding v. Outbreedingf. Sources of new genetic variationi. Mutationsii. Exon shufflingiii. Horizontal gene transferiv. Changes in repetitive sequencesg. DNA fingerprintingCurrent LectureI. Population genetics: became an important area of study in 1920s/1930s. Defined as the study of genetic variation within the gene pool and how it changes from one generation to the next. a. Composition of population genetics: consists of concepts from Mendel’s laws of inheritance, molecular genetics, and the ideas of Darwin. b. Gene pool: all the alleles of every gene in a population. Only individuals that reproduce contribute to the gene pool of the next generation. II. Populations: a population is a group of individuals of the same species that occupy the same region and can interbreed with each other. a. Characteristics: dynamic units that change from one generation to the next. May change in size, geographic location, or genetic composition. b. Demes: also called a local population. Likelier to breed with each other than with members of the general population. These populations are ofen separated from each other by geographic barriers. III. Allele and gene frequencies: equations have been developed to evaluate allele and gene frequencies in populations.a. Polymorphism: many traits display variation within a population (ex: happy face spider). Due to two or more alleles that influence the phenotype (genetic variation). Monomorphism refers to a gene that existspredominantly as a single allele.b. Single-nucleotide polymorphism: account for 90% of variation between people. In humans, a gene that is 2000-3000 base pairs in length contains an average of 10 different polymorphic sites. c. Allele frequencyi. Equation: (number of copies of an allele in a population/total number of all alleles for that gene in a population).ii. Example: population of 100 frogs. 64 have genotype GG, 32 have Gg, and 4 have gg. Total number of copies of an allele (g) is (2*4)+32. Total number of all alleles for this gene is (2*64+2*32+2*4). Frequency of allele g is 0.20 or 20%. d. Genotype frequencyi. Equation: (number of individuals with genotype/total number of individuals in population).ii. Example: the same population of 100 frogs with the same genotypes. 4 frogs have the gg genotype, so the answer is 4/100 or 4%. e. Trends in frequencies: allele and genotype frequencies are always less than or equal to 1. For monomorphic genes the allele frequency for a single allele would be equal or close to 1.0. For polymorphic genes the frequencies of all alleles should add up to 1.0. f. Hardy-Weinberg equilibrium: equation that relates allele and genotype frequencies in a population. In reality no natural population is in Hardy-Weinberg equilibrium. i. Conditions: no new mutations, no genetic drif (very large population), no migration, no natural selection, random mating. ii. Equation: p2 + 2pq + q2 = 1 iii. Example: frog example: GG = p2= (0.8)2 = 0.64. Gg = 2pq = 2(0.8*0.2) = 0.32. gg = q2 = (0.2)2 = 0.04. Answer is (0.64+0.32+0.04) = 1.0g. X2 test: can be used in place of the HW equilibrium or to verify that a population is in Hardy-Weinberg equilibrium. If the chi square value is high, the population is in disequilibrium (may indicate evolutionary change). i. Equation: X2 = (O1 – E1)2/E1 + (O2 – E2)2/E2 … + (On – En)2/En where O means observed value and E means expected value. ii. Example: human blood type called the MN type, determined by codominant alleles M and N. If an Inuit population in Greenland has 168 MM people, 30 MN people, and 2 NN people what is the conclusion about this population? iii. Results: a low X2 value will ofen mean that the null hypothesis should be rejected and the data is of statistical significance. A highX2 value usually indicates that the null hypothesis should be accepted and the data is not of statistical significance.IV. Patterns of evolutiona. Microevolution: changes in a population’s gene pool from generation to generation. Driven by: mutations, random genetic drif, migration, naturalselection and non-random mating. b. Natural selection: defined in the 1850s by Charles Darwin and Alfred Russell Wallace as “survival of the fittest” and the “struggle for existence”.In other words, individuals that are most adapted to their particular environment will survive and reproduce. Modern definition relates molecular genetics to the phenotypes of individuals and focus on an individual’s ability to reproduce. c. Genetic drif: the fact that allele frequencies may drif from generation to generation as a matter of random chance. Over the long run genetic drif favors either the loss or the fixation of an allele. The rate depends on the