Genetic Linkage


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Genetic Linkage

  1. 1. Genetics ~Part II Genetic Recombination & Gene Linkage
  2. 2. Genetic Recombination <ul><li>Genetic recombination occurs during meiosis </li></ul><ul><ul><li>the formation of sperm and egg cells </li></ul></ul><ul><li>Homologous chromosomes become paired </li></ul><ul><li>Form a tetrad </li></ul><ul><li>While they are wrapped together, the chromosomes may break </li></ul><ul><li>Each may swap a portion of its genetic material for the matching portion from its mate. </li></ul>
  3. 4. Crossing Over <ul><li>This form of recombination is called crossing-over </li></ul><ul><li>When the chromosomes separate, each has picked up new genetic material from the other </li></ul><ul><li>The alleles it specifies are now different than before crossing-over </li></ul>
  4. 6. Linkage <ul><li>Tracking movement of genes during crossing-over allows determination of roughly how far apart two genes are on a chromosome. </li></ul><ul><li>There are more chances for a break to occur between two genes that lie far apart </li></ul><ul><ul><li>Therefore, there is a higher probability of crossing over </li></ul></ul><ul><ul><li>Genes that lie far apart are likely to end up on two different chromosomes </li></ul></ul><ul><li>Genes that lie very close together are less likely to be separated by a break and crossing-over. </li></ul><ul><li>Genes that tend to stay together during recombination are said to be linked . </li></ul>
  5. 7. Genetic Markers <ul><li>Geneticists often use a linked gene to help detect the presence of another gene of interest </li></ul><ul><ul><li>For example, to determine the probability of a genetic disease when a direct test is not available. </li></ul></ul><ul><li>One gene in a linked pair is used to infer the presence of the other </li></ul><ul><ul><li>usually a disease-causing gene </li></ul></ul><ul><li>The identified gene serves as a &quot; marker &quot; </li></ul>
  6. 8. Independent Assortment <ul><li>After the chromosomes separate in meiosis, they are parceled out to individual gametes </li></ul><ul><li>Each chromosome moves independently of the others  </li></ul><ul><ul><li>Independent assortment </li></ul></ul><ul><li>Assortment takes place for each of the 23 pairs of human chromosomes. </li></ul><ul><li>Any single human egg or sperm receives one of two possible chromosomes 23 times </li></ul><ul><ul><li>The total number of different possible chromosome combinations is 2 23, over 8 million </li></ul></ul>
  7. 10. Analyzing Crosses <ul><li>If you analyze a cross involving two genes, A & B, the analysis is different if the 2 genes are on a single chromosome </li></ul><ul><li>If the two genes are on different chromosomes, analysis is straightforward as we have seen in Mendellian crosses </li></ul><ul><li>EXAMPLE: </li></ul><ul><ul><li>AaBb x aabb </li></ul></ul><ul><ul><li>aabb produces only ab gametes </li></ul></ul><ul><ul><li>AaBb produces equal frequencies of 4 types of gametes which lead to 4 types of progeny </li></ul></ul>
  8. 11. ab aabb  ab ab 25% aB aaBb  ab aB 25% Ab Aabb  ab Ab 25% AB AaBb  ab AB 25% Progeny phenotype Progeny genotype Gamete from aabb parent Gamete from AaBb parent Frequency
  9. 12. Crosses Involving Linked Genes <ul><li>If A & B are very close together on one chromosome, than the original combinations of A & B alleles in the heterozygous parent will remain together in the progeny </li></ul><ul><li>If A & B are close together on the same chromosome, recombination will occur during meiosis and four types of gametes will be produced </li></ul>
  10. 14. Case 1 Case 2 A - B - A - b - - B - b - a - a Both are Genotype AaBb
  11. 15. Notation for Linked Genes <ul><li>The AaBb type of notation cannot distinguish between these different possibilities </li></ul><ul><li>Other notations show the combinations of A & B alleles on each chromosome. </li></ul>CASE 1 AB or AB/ab Ab CASE 2 Ab or Ab/aB aB If A & B are wild-type, use (+): ++ or ++/ab ab +b or +b/a+ a+
  12. 16. Parental Types <ul><li>These allele combinations are the parental types </li></ul><ul><li>They are called parental types because they are the allele combinations that the individual in case 1 or 2 inherited from his or her parents </li></ul>
  13. 17. Recombination <ul><li>As noted, if A & B are close together on the same chromosome, recombination will occur during meiosis </li></ul><ul><li>Four types of gametes will be produced </li></ul>
  14. 18. Case 1 Gametes <ul><li>ab/++ will produce: </li></ul>r/2 recombinant +b r/2 recombinant a+ p/2 parental ++ p/2 parental ab Frequency Type Gamete
  15. 19. Case 2 Gametes <ul><li>a+/+b will produce: </li></ul>r/2 recombinant ++ r/2 recombinant ab p/2 parental +b p/2 parental a+ Frequency Type Gamete
  16. 20. Parental vs. Recombinant Types <ul><li>What changes between the 2 cases is which gametes are parental and which recombinant </li></ul><ul><li>The genotypes which are parental or recombinant depend upon the genetic constitution of the heterozygous parent </li></ul><ul><li>Note that the two parental types are produced with equal frequency as are the recombinant types </li></ul><ul><li>p + r = 1 </li></ul>
  17. 21. Test Cross <ul><li>Test crosses for gene mapping cross a heterozygote (where recombination takes place) with a homozygous recessive </li></ul><ul><li>This results in progeny whose genotypes can be determined from their phenotypes </li></ul>
  18. 22. Sample Test Cross <ul><li>If you cross (ab/++) x (ab/ab), 4 types of progeny will be observed: </li></ul>r/2 recombinant +b +b/ab r/2 recombinant a+ a+/ab p/2 parental ++ ++/ab p/2 parental ab ab/ab Frequency Type Progeny Phenotype Progeny Genotype
  19. 23. Why A Test Cross? <ul><li>ab/ab produces only one type of gamete: ab </li></ul><ul><li>Since that parent is homozygous recessive, the genotypes of the progeny are directly revealed in the phenotypes. </li></ul>
  20. 24. Other Mapping Crosses <ul><li>What would happen if the homozygous parent were homozygous dominant ? </li></ul><ul><li>In Case 2, the parental and recombinant types would be exchanged. </li></ul><ul><ul><li>Parental types = (a+/ab) & (+b/ab) </li></ul></ul><ul><ul><li>Recombinant types = (ab/ab) & ++/ab . </li></ul></ul><ul><li>Using crosses like this, you can measure recombination frequency. </li></ul>
  21. 25. Recombination Frequency <ul><li>Recombination frequency is defined as: </li></ul><ul><li>number of recombinants </li></ul><ul><li> total number of progeny </li></ul><ul><li>or </li></ul><ul><li> r__ </li></ul><ul><li> p + r </li></ul><ul><li>Recombination frequency is expressed as a % recombination or . . . </li></ul><ul><li>In map units measured in centimorgans (cM) = (r/p+r) x 100 </li></ul>
  22. 27. Recombination Frequency & Map Distance <ul><li>Recombination frequency between genes increases with increasing distance between genes </li></ul><ul><li>This can be used to create genetic maps of chromosomes </li></ul><ul><ul><li>Can determine gene order and distance </li></ul></ul><ul><li>When 2 genes are unlinked (on different chromosomes or very far apart on the same chromosome) the recombination frequency = 50% </li></ul>
  23. 28. Understanding Frequency <ul><li>Why isn't the recombination frequency of unlinked genes 100%? </li></ul><ul><li>Consider the case where A and B are on different chromosomes </li></ul><ul><li>All 4 types of gametes are produced with equal frequency </li></ul><ul><li>No matter which are the parental or recombinant types, each type represents 50% of the total </li></ul><ul><li>Therefore: 0% < recombination freq. < 50% </li></ul>
  24. 29. Genetic Mapping <ul><li>Near 0% recombination frequency means the genes are very tightly linked </li></ul><ul><li>50% recombination frequency means the genes are entirely unlinked </li></ul><ul><li>The recombination frequency can never be exactly 0% </li></ul><ul><ul><li>that would require an infinite number of progeny </li></ul></ul><ul><ul><li>If no recombinants are observed in n progeny, you can only conclude that the recombination frequency is < 1/n </li></ul></ul><ul><li>In humans, 1 cM is roughly = 1 million nucleotide pairs (bp) of DNA </li></ul>
  25. 31. Linkage Problems - Example <ul><li>In a plant, leaf color and leaf shape are controlled by two linked genes. </li></ul><ul><li>Leaves of the wild-type plant are red. </li></ul><ul><li>A recessive mutation in this gene causes white leaves. </li></ul><ul><li>Wild-type leaves are pointed </li></ul><ul><li>A recessive mutation in this gene causes them to be smooth. </li></ul>
  26. 32. Linkage Problem (Cont.) <ul><li>Pure breeding white, smooth is crossed with pure breeding wild type </li></ul><ul><li>F1: all red, pointed </li></ul><ul><li>Test cross red, pointed x pure breeding white, smooth </li></ul><ul><li>Gives F2: 40 white, smooth 36 red, pointed 10 white, pointed 14 red, smooth </li></ul>
  27. 33. Try It! <ul><li>What is the recombination frequency between the gene for color and for shape? </li></ul>
  28. 34. Strategies <ul><li>First, assign genotype symbols. </li></ul><ul><li>Since the mutations are recessive to wild-type, use + for the wild type allele & lower case letters for mutant alleles: w = recessive white color s = recessive smooth shape </li></ul><ul><li>So, the first cross is: (ws/ws) x (++/++) giving red, pointed progeny, (ws/++) </li></ul>
  29. 35. The Test Cross <ul><li>The second cross is (ws/++) x (ws/ws) </li></ul><ul><li>The progeny genotypes can be determined from their phenotypes </li></ul><ul><li>Determine which gamete types are parental and which are recombinant </li></ul><ul><ul><li>(ws) white, smooth and (++) red, pointy are parental </li></ul></ul><ul><ul><li>(w+) white, pointy and (+s) red, smooth are recombinant </li></ul></ul>
  30. 36. Solving <ul><li>Therefore, recombination frequency = </li></ul><ul><li> (10 + 14) </li></ul><ul><li> (10 + 14) + (40 + 36) </li></ul><ul><li>= .24 % or 24 cM </li></ul>