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Instructor: Dr. Olabisi Textbook: Genetics: From Genes to Genome by Hartwell Linkage, Recombination, and the Mapping of Genes on ChromosomesDrosophila melanogaster - There are 4homologous pairs of chromosomes o 2 pairs of large autosomes o 1 pair of very small autosomes o A pair of sex chromosome - Females normally have two X chromosomes - Males -> one X and a tiny Y chromosome Human Genome - It is made up of 23chromosome pairs with a total of about 3 billion DNA base pairs - There are an estimated 20,000-25,000 human protein-coding genes Linkage and Recombination - Genes linked together on the samechromosome usually assort together- Linked genes may become separated by recombination Genetic Linkage - The phenomenon in which genes that are close together on the same chromosome tend to be transmitted as a unit - The proximity of two or more markers on a chromosome; the closer together the markers are, the lower the probability that they will be separated by chromosomes Independent assortment - When genes are on separatechromosomes, or very far apart on the same chromosomes, they assort independently due to crossing over (homologous recombination) o Because of the random orientation of homologous chromosome pairs during meiosis - For example, o AaBb -> AB, Ab, aB, ab o 4 combinations Linkage - When genes are close together on the same chromosome, they are said to be linked- The genes do not independently assort - Two genes on the same chromosome segregate together - For example, o AaBb -> AB, ab
Instructor: Dr. Olabisi Textbook: Genetics: From Genes to Genome by Hartwell o 2 combinations - Genes on separate chromosomes are never linked Recombination and distance - Two very close-together genes will have very few recombinationevents and be tightly linked, while two genes that are slightly further apart will have more recombination events and be less tightly linked - The frequency with which genes become separated reflects the physical distance between them o Crossovers during meiosis happen at more or less random positions along the chromosome, so the frequency of crossovers between two genes depends on the distance between them Properties of Linked vs. Unlinked Genes - Linked genes o Parentals > Recombinants (RF < 50%) o Deviation from 1:1:1:1 segregation in F2 indicates the genes are linked o Linked genes must be syntenic and sufficiently close together on the same chromosome so that they do not assort independently Syntenic genes: genes located on the same chromosome - Unlinked genes o Parentals = Recombinants o Occurs either when two genes are on different chromosomes or when they are sufficiently far apart on the same chromosomes that at least one crossover occurs between them in every meiosis Recombination frequencies - Reflect distances between two genes - The recombination frequency is relatively constant between homologous chromosomes - For a given chromosome, N number of breaks will occur, but wherethey will occur is random - Could be used as a gauge of the physical distance separating any two genes on the same chromosome - 1 %RF = 1 map unit (m.u.) = 1 centiMorgan (cM) Two point crosses - Can establish the order of linked genes and the distances between them through pairwise analysis of recombination frequencies Limitations of two point crosses
Instructor: Dr. Olabisi Textbook: Genetics: From Genes to Genome by Hartwell - Difficult to determine gene order if two genes are close together - Actual distances between genes do not always add up- Pairwise crosses are time and labor consuming Three-point crosses - Can refine map distances and reveal the existence of crossover interference, a phenomenon that helps to distribute among all chromosomes the limited number of crossovers that occur in each meiosis - Provide faster and more accurate mapping Analyzing the results of a three-point cross - Testcross progeny have four sets of reciprocal pairs of genotypes o Most frequent pair has parentalconfiguration of alleles o Least frequent pair results from double crossovers o Examination of double crossoverclass reveals which gene is in the middle Inferring the location of crossover event - Examine numbers of progeny - Compare configuration of alleles at two genes at a time to parental configuration Do genetic maps correlate with physical reality? - Order of genes revealed by genetic mapping corresponds to the actual order of genes along the chromosome o Provide an accurate picture of gene order on a chromosome - Actual physical distances between genes—that is, the amount of DNA separating them—does not always correspond linearly to genetic map distances o Double, triple, and more crossovers o 50% limit on observable recombination frequency o Recombination hotspots Drosophila melanogaster - Has four linkage groups - When many genes per chromosome have been mapped, a linkage groupis synonymous with a chromosome How do geneticists indicate the location of a gene? - Cytogenetic Locationo The chromosome on which the gene can be found o The arm of the chromosome
Instructor: Dr. Olabisi Textbook: Genetics: From Genes to Genome by Hartwell o A gene’s molecular address pinpoints the location of that gene in terms of base pairs Recombination: A result of crossing-over during meiosis - Frans Janssens – 1909, o Observed chiasmataat chromosomes during prophase of meiosis I - T. H. Morgan o Suggested chiasmata were sites of chromosome breakage and exchange- H. Creighton and B. McClintock (corn) and C. Stern (Drosophila) – 1931, o Direct evidence that genetic recombination depends on reciprocal exchange of chromosomes Physical markers Were used to identify specific chromosomes Cytologically visible abnormalities that make it possible to keep track of specific chromosome parts from one generation to the next Crossing-over helps establish physical linkages between homologous chromosomes needed to prevent nondisjunction Genetic markers Were used as points of reference for recombination Genes identifiable through phenotypic variants that can serve as points of reference in determining whether particular progeny are the result of combination Why Recombination - Recombination contributes to genetic diversity by reshuffling the alleles of genes between homologous chromosomes - Ensure that chromosomes segregate properly when they are transmitted between parents and their progeny When does recombination take place? - Prophase of meiosis I, very high frequency o Recombination occurs when chromatids of homologous chromosomes exchange parts during prophase of meiosis I- Interphase of mitosis, low frequency - For genes linked, RF < 50% - Genes are unlinked if show 50% recombination = independent segregation - Genes are completely linked if show 0% recombinationo Very rare if one looks at very large sample of offspring Recombination frequencies between two genes never exceed 50%
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School: University of Delaware
Course: Genetic and Evolutionary Biology
Professor: Erica Selva
Term: Fall 2015
Description: These notes cover what's going to be in our next exam
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