1. LECTURE 22 LARGE-SCALE CHROMOSOME CHANGES II  chapter 15  overview  chromosome number  chromosome structure  problems

2. CHANGES IN CHROMOSOME NUMBER  what are the genotypic & phenotypic probabilities in the progeny of a P cross A/A/A/a  A/A/A/a ?  P gametes: P ( A/A ) = P ( A/a ) = ½, P ( a/a ) = 0  F 1 genotypes: P ( A/A/A/A ) = (½) 2 = ¼ P ( A/A/A/a ) = 2(½) 2 = ½ P ( A/A/a/a ) = (½) 2 = ¼  F 1 phenotypes:all A  A/A/a/a ?  A/a/a/a ? } work out these ones for next class  autopolyploids

3.  3 classes of chromosome change OVERVIEW  

4.  2 general questions to consider...  is the genome complete?  is the genome balanced? OVERVIEW

5. CHANGES IN CHROMOSOME STRUCTURE  implications  chromosome structure mutations  phenotypes 1.abnormal gene #  segmental aneuploids 2.abnormal gene environment  position effect 3.break points  disrupt gene function

6. CHANGES IN CHROMOSOME STRUCTURE  things to keep in mind  each chromatid is has a single DNA molecule  need either...  2+ double strand breaks  crossing over between repetative sequences  chromosome breakage  ends highly reactive (normal telomeres not)  double strand breaks are lethal unless repaired  repaired by joining broken ends

7. CHANGES IN CHROMOSOME STRUCTURE  more things to keep in mind  repair can restore original sequence or  generate rearrangement  acentric products are lost & inviable  dicentric products are broken & inviable  rearrangements can be  spontaneous  induced by radiation... X- or  -rays  mainly studied in heterozygotes

8. CHANGES IN CHROMOSOME STRUCTURE  2 types of rearrangements 1.unbalanced change gene dosage  deletions  uncover deleterious alleles  usually lethal  duplications  extra material  evolutionary divergence

9. CHANGES IN CHROMOSOME STRUCTURE  2 types of rearrangements 2.balanced change gene dosage  inversions  reduced fertility  reduced recombination in inverted region  translocations  reorganizes linkage  50% sterility fertility  novel linkage of genes on translocated chromosomes

10. CHANGES IN CHROMOSOME STRUCTURE  origins of rearrangements by 2 processes 1.break / rejoining  spontaneous  radiation

11. CHANGES IN CHROMOSOME STRUCTURE  origins of rearrangements by 2 processes 1.break / rejoining  spontaneous  radiation 2.crossing over  illegitimate

12. CHANGES IN CHROMOSOME STRUCTURE  visualization in heterozygotes  strong pairing affinity during meiotic prophase I  abnormal patterns seen in rearrangement heterozygotes (–/+)

13. CHANGES IN CHROMOSOME STRUCTURE  biological importance  research tools   new combinations of genes  mapping  recombination suppression  mutant rescue  applied research  medicine & agriculture  evolutionary significance  genome reshuffling

14. CHANGES IN CHROMOSOME STRUCTURE  deletions  1 chromosome break  terminal  2 chromosome break  interstitial

15. CHANGES IN CHROMOSOME STRUCTURE  deletions  intragenic  within 1 gene  do not revert (  point mutations)  can be viable if gene not vital  multigenic  > 1 gene  do not revert  usually homozygous lethal  sometimes heterozygous lethal

16. CHANGES IN CHROMOSOME STRUCTURE  deletions  multigenic  > 1 gene  uncovers recessive alleles on homologue  pseudodominance  deletion mapping

17. CHANGES IN CHROMOSOME STRUCTURE  deletions  multigenic  > 1 gene  uncovers recessive alleles on homologue  pseudodominance  deletion mapping

18. CHANGES IN CHROMOSOME STRUCTURE  deletions  multigenic  > 1 gene  deletion mapping ~ linkage maps

19. CHANGES IN CHROMOSOME STRUCTURE  deletions  multigenic  > 1 gene  deletion mapping ~ human disease, e.g. : cri du chat syndrome

20. CHANGES IN CHROMOSOME STRUCTURE  duplications (2 chromosome breaks)  adjacent, same order  tandem  adjacent, reverse order  reverse

21. CHANGES IN CHROMOSOME STRUCTURE  duplications  intragenic  within 1 gene  do not revert (  point mutations, see below)  can be viable if genetic balance not critical  multigenic  > 1 gene  do not revert (see below)  homozygous lethal if genetic balance critical  can be heterozygous lethal if balance critical

22. CHANGES IN CHROMOSOME STRUCTURE  duplications  illegitimate recombination possible, e.g. : Bar

23. CHANGES IN CHROMOSOME STRUCTURE  duplications  important for gene evolution, e.g. : human hemoglobin genes

24. CHANGES IN CHROMOSOME STRUCTURE  duplications  important for gene evolution, e.g. : human hemoglobin genes

25. CHANGES IN CHROMOSOME STRUCTURE  inversions  does not include centromere  paracentric  does include centromere  pericentric

26. CHANGES IN CHROMOSOME STRUCTURE  inversions  does not include centromere  paracentric A B C D E F G H 

27. CHANGES IN CHROMOSOME STRUCTURE  inversions  does not include centromere  paracentric A B C D E F G H  

28. CHANGES IN CHROMOSOME STRUCTURE  inversions  does not include centromere  paracentric A C B D E F G H

29. CHANGES IN CHROMOSOME STRUCTURE  inversions  does include centromere  pericentric A B C D E F G H 

30. CHANGES IN CHROMOSOME STRUCTURE  inversions  does include centromere  pericentric A B C D E F G H  

31. CHANGES IN CHROMOSOME STRUCTURE  inversions  does include centromere  pericentric A B F E D C G H

32. CHANGES IN CHROMOSOME STRUCTURE  inversions  no change in total genetic material  breakpoints can (but not always) disrupt genes  no disruption  viable homozygotes  disruption  heterozygotes only (majority)  do not revert  recombination in inversion  segm. aneuploidy  recombinant gametes lethal , fertility   recombination suppression

33. CHANGES IN CHROMOSOME STRUCTURE  inversions  breakpoints between genes

34. CHANGES IN CHROMOSOME STRUCTURE  inversions  breakpoints between genes... disruption of 1  breakpoints within genes... gene fusion

35. CHANGES IN CHROMOSOME STRUCTURE  inversions  loops

36. CHANGES IN CHROMOSOME STRUCTURE  inversions  loops

37. CHANGES IN CHROMOSOME STRUCTURE  inversions  loops

38. CHANGES IN CHROMOSOME STRUCTURE  inversions  crossing over in a paracentric inversion heterozygote

39. CHANGES IN CHROMOSOME STRUCTURE  inversions  crossing over in a paracentric inversion heterozygote  1 normal  viable  1 inversion  viable  1 acentric  lost  1 dicentric  2 lethal deletion products

40. CHANGES IN CHROMOSOME STRUCTURE  inversions  crossing over in a pericentric inversion heterozygote

41. CHANGES IN CHROMOSOME STRUCTURE  inversions  crossing over in a pericentric inversion heterozygote  1 normal  viable  1 duplication  lethal  1 deletion  lethal  1 inversion  viable

42. CHANGES IN CHROMOSOME STRUCTURE  translocations (reciprocal or Robertsonian)  no change in total genetic material  do not revert  meiosis  segmental aneuploidy  lethality  semi-sterility  rearrangement of linkage groups  can restructure genomes

43. CHANGES IN CHROMOSOME STRUCTURE  translocations  heterozygotes  adjacent-1  4 lethal  adjacent-2  rare, 4 lethal  alternate  2 normal + 2 carrier

44. CHANGES IN CHROMOSOME STRUCTURE  translocations  pseudolinkage observed from test cross of translocation heterozygote: a/; a + b + /b  a/a; b/b

45. CHANGES IN CHROMOSOME STRUCTURE  translocations  position-effect variegation

46. PROBLEMS  #1-55 on pp. 512-520  consider (read & think about) all of the questions  at the very least you should do #s 22, 23, 26, 40, 49