GEN 3022 1st Edition Lecture 38 Outline of Last Lecture I Genetic basis of cancer a Characteristics b Statistics II Viruses that cause cancer a Efficiency of causing cancer b Acutely transforming viruses c Rous sarcoma virus III Oncogenes a Development b Patterns of expression c Conversion of proto oncogenes i Missense mutation ii Gene amplification iii Chromosomal locations iv Viral integration IV Tumor suppressor genes a Inactivation of tumor suppressor genes i Mutation in gene itself ii DNA methylation iii Aneuploidy b Genome maintenance i Checkpoint proteins ii Cyclins and cyclin dependent kinases iii DNA repair enzymes c p53 gene i Functions ii Apoptosis d Retinoblastoma i Two types ii Two hit model V Multiple genetic changes a Development pattern of cancers These 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 study c Genetic changes leading to cancer VI Inherited forms of cancers a Predisposition for developing cancer b Loss of heterozygosity Outline of Current Lecture I Population genetics a Composition of population genetics b Gene pool II Populations a Characteristics b Demes III Allele and gene frequencies a Polymorphism b Single nucleotide polymorphism c Allele frequency i Equation ii Example d Genotype frequency i Equation ii Example e Trends in frequencies f Hardy Weinberg equilibrium i Conditions ii Equation iii Example 2 g X test i Equation ii Example iii Results IV Patterns of evolution a Microevolution b Natural selection c Genetic drif i Bottleneck effect ii Founder effect d Migration e Non random mating i Assortative mating ii Positive assortative mating iii Negative assortative mating iv Inbreeding v Outbreeding f Sources of new genetic variation i Mutations ii Exon shuffling iii Horizontal gene transfer iv Changes in repetitive sequences g DNA fingerprinting Current Lecture I II III 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 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 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 exists predominantly 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 frequency i 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 frequency i 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 HardyWeinberg 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 0 2 g X 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 high IV X2 value usually indicates that the null hypothesis should be accepted and the data is not of statistical significance Patterns of evolution a Microevolution changes in a population s gene pool from generation to generation Driven by mutations random genetic drif migration natural selection 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 population size and on the initial allele frequencies i Bottleneck effect when a population is reduced dramatically by something like a natural disaster Individuals are eliminated regardless of genotype The point when the