BSCI222 Genetics Week 5 Notes
BSCI222 Genetics Week 5 Notes BSCI222
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This 7 page Class Notes was uploaded by Colin Fields on Sunday October 2, 2016. The Class Notes belongs to BSCI222 at University of Maryland taught by Dr. Paczolt in Fall 2016. Since its upload, it has received 3 views. For similar materials see Genetics in Biology at University of Maryland.
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Date Created: 10/02/16
BSCI222 Genetics Chapter 7 Linkage and Mapping 1. 7.1 Linked Genes Do Not Assort independently a. Genes located close together on a chromosome are called linked genes i. These genes are close enough together that during crossover there is a statistically significant chance that both genes will be in the same segments swapped b. Groups or sequences of linked genes are called a linkage group c. Linked genes will produce a deviation from the 9:3:3:1 phenotypic ratio normally observed with a dihybrid cross 2. 7.2 Linked Genes Segregate Together While Crossing Over Produces Recombination Between Them a. Notation for Crosses with Linkage i. 1. http://www.mathbench.umd.edu/modules/prob- stat_recombination/page05.htm b. Complete Linkage Compared With Independent Assortment i. Consider a cross between a homozygous dominant for two traits and a homozygous recessive for both traits ii. The F1s are all heterozygous with dominant alleles on one chromosome and recessive alleles on the other iii. Crossing of the F1s will produce only offspring that have the parental phenotypes, either double dominant or double recessive, because there is no gamete that contains a mix or dominant or recessive alleles if there is complete linkage iv. Offspring that exhibit the traits of the parental generation are nonrecombinant progeny v. Offspring that exhibit mixed traits are recombinant progeny c. Crossing Over with Linked Genes i. The percentage of recombination for nonlinked genes is equal to half the percent of meiosis in which there is crossing over ii. The percentage of recombination for linked genes is equal to half the percent of meiosis in which crossover takes place between the linked genes d. Calculating Recombination Frequency i. Recombination frequency equals the % of progeny that are recombinant e. Coupling and Repulsion i. Coupling is when the wild type alleles are found on the same chromosome and mutant alleles are found on the other. This is also called a cis configuration ii. Repulsion is when the chromosomes contain a wild type and a mutant allele on them. This is also called a trans configuration f. Evidence for the Physical Basis of Recombination i. Observable differences between chromosomes can be used to track where specific regions of the chromosomes end up after crossing over g. Predicting the Outcomes of Crosses with Linked Genes i. Recombinant frequency divided by two yields the % of gametes containing each of the two possible recombinations ii. The remaining % of gametes will be nonrecombinant iii. The product of each gamete’s frequency for a combination gives the probability of that specific genotype h. Testing for Independent Assortment i. Chi-Squared Test of Independence 1. a. n = the count from the subset b. e is the expected count from the subset c. df is the degrees of freedom d. r is the number of rows i. the combinations of one allele go here e. c is the number of columns i. the combinations of the other allele go here i. Gene Mapping with Recombination Frequencies i. Genetic maps are made using the phenomenon of recombination 1. Units are centiMorgans (cM) = 1 map unit = 1% recombination 2. Measured rates are approximately additive ii. Physical maps are made using the physical distance along a chromosome iii. Maps can be used to find order of genes on a chromosome by finding what combination results in the correct distances between genes 3. 7.3 A Three-Point Testcross Can Be used to Map Three Linked Genes a. Constructing a Genetic Map with the Three-Point Testcross i. Determining Gene Order 1. Identify the nonrecombinant progeny (two most numerous phenotypes 2. Identify double cross over progeny 9two least numerous phenotypes) 3. Find which of the three characteristics in which the double cross over progeny and the non recombinant progeny differ 4. The characteristics that differs is the middle gene ii. Determining the Locations of Crossovers 1. Identify the characteristic that the single cross over progeny have different than the nonrecombinant progeny 2. The gene for that phenotype is on the other side of a crossover from the other two genes iii. Calculating the Recombination Frequencies 1. # of recombinants / total number * 100 iv. Interference and the Coefficient of Coincidence 1. Interference is the degree to which one crossover interferes with additional crossovers 2. Coefficient of Coincidence is the ratio of observed double crossovers to the expected double crossovers 3. Interference is 1 – the coefficient of coincidence 4. There can be negative interference b. Effect of Multiple Crossovers i. Crossover can happen with multiple strands of chromatids in a homologous pair 1. Two-strand double crossover produces 0% recombinant gametes 2. Three-strand double crossover produces 50% recombinant gametes 3. Four-strand double crossover produces 100% recombinant gametes 4. The average of these possible combinations is 50% ii. Some multiple crossovers go undetected making map distance an underestimation of true physical separation distance iii. Mapping functions can be made to somewhat correct for this error by assuming a normal distribution for rare events c. Mapping Human Genes i. Extensive and complicated pedigree analysis is done to identify linkage because humans are an awful model organism ii. lod score is used to determine the probability that genes are actually linked 1. the probability of obtaining observed results with independent assortment is calculated 2. the probability of obtaining observed results with linkage at a specific recombination frequency is calculated 3. the log base 10 of the ration between liked probability and independent probability is the lod score 4. a lod score > 3 is usually considered convincing evidence for linkage (linkage is 1000x as likely to produce the results than independent assortment) d. Mapping with Molecular Markers i. Genetic markers are variable genes with easily observable phenotypes for which inheritance can be studied ii. Specific markers in the DNA itself are monitored just like phenotypes and the linkage and map distance is found the same way e. Genes Can Be Located with Genomewide Association Studies i. Linkage analysis is the analysis of how a phenotype is inherited relative to how other alleles are inherited ii. Genomewide Association Studies do the same thing as linkage studies but consider the entire genome instead of a small portion 1. This does not trace inheritance but rather trances associations between a trait and specific complements of alleles in a population iii. Haplotype is a specific set of linked alleles 1. The nonrandom association between alleles in a haplotype is linkage disequilibrium 4. 7.4 Physical-Mapping Methods Are Used to Determine the Physical Positions of Genes on Particular Chromosomes a. Somatic-Cell Hybridization i. A human and non human (usually mouse) cell are fused together resulting in a cell with two nuclei called a heterokaryon which eventual has the nuclei fuse ii. The fused nucleus gradually loses chromosomes as the cell divides until it eventually stabilizes iii. By comparing differences between these hybrid cells which have different sets of human chromosomes traits can be assigned to chromosomes b. Deletion Mapping i. The relation between the absence or altered expression of a phenotype when a specific region of a chromosome is deleted can tell if the gene for that trait are located at that position ii. An individual who is homozygous for a recessive trait is crossed with an individual who is dominant for that trait but has the region deleted from one of their chromosomes iii. If the trait is encoded in the deleted region half of the offspring will be recessive instead of all dominant c. Physical Chromosome Mapping Through Molecular Analysis i. A radioprobe complementary to gene of interest is inserted into a cell. It thing aligns with the gene of interest thereby locating it 5. Recombination Rates Exhibit Extensive Variation a. Rates of recombination are usually lower within important genes or regions but there are frequently hotspots for recombination close to these genes b. Not all chromosomes, organisms, or sexes are created equal in terms of recombination frequency