1. LECTURE 10B: MEIOSIS IN ACTION

2. first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

3. first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

4. first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

5. first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

6. first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

7. first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

8. first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

9. first meiotic division: prophase: leptotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

10. first meiotic division: prophase: zygotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

11. first meiotic division: prophase: pachytene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

12. first meiotic division: prophase: pachytene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

13. first meiotic division: prophase: diplotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

14. first meiotic division: prophase: diplotene normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

15. first meiotic division: metaphase I normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

16. first meiotic division: metaphase I normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

17. first meiotic division: anaphase I normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

18. first meiotic division: telophase I normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

19. first meiotic division: telophase I normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

20. first meiotic division: telophase I: first polar body normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

21. first meiotic division: telophase I: first polar body normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

22. first meiotic division: telophase I: first polar body normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

23. second meiotic division: metaphase II normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

24. second meiotic division: metaphase II normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

25. second meiotic division: anaphase II normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

26. second meiotic division: telophase II normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

27. second meiotic division: telophase II normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

28. second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

29. second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

30. second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

31. second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

32. second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

33. second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

34. second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

35. second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

36. second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

37. second meiotic division: second polar bodies normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

38. fertilization normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

39. fertilization normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

40. fertilization normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

41. fertilization normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

42. fertilization normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

43. fertilization normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

44. fertilization normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

45. fertilization normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

46. fertilization normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

47. fertilization normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

48. fertilization normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

49. fertilization normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

50. fertilization normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

51. fertilization normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

52. cleavage (mitosis): prophase normaltrisomy 21 chromosome 21 other chromosomes © 2003 H. NUMABE M.D.

55. Down Syndrome or Trisomy 21 Karyotype 47,XY,+21 The term “Mongolism” is not appropriate

56. Robertsonian Translocations Other chromosomal forms of Down syndrome - ?inheritance Can result in Down syndrome

57. Trisomy 13

58. Polydactyl of Trisomy 13

59. Trisomy 13 at age 7 yrs. Trisomy 13 showing cleft lip/palate

60. Trisomy 18

61. Overlapping fist Trisomy 18

62. Other syndromes with physical finding also found in +13 and +18 Cleft lip / palate holoprosencephaly Cleft lip / palate & cyclopsia

63. When good chromosomes go bad Chromosomal Rearrangements

64. Chromosome Abnormalities: Structural rearrangements Chromosome breakage with subsequent reunion in a different configuration –Balanced no loss or gain of genetic information position change no phenotype consequences (except when there is a position effect  gene disruption) reproductive consequences Unbalanced –loss or gain or chromosome material –abnormal phenotype association

65. Robertsonian TranslocationReciprocal Translocation vs. Common form of structural rearrangements

66. Reciprocal Translocation Balanced translocation results in a position effect only i.e. the exchange of chromosome material between 2 chromosomes no loss or gain of genetic information, usually no phenotype effect (unless there is a position effect resulting in gene disruption)

67. Examples of Balanced Structural Rearrangement

68. Reciprocal Translocations: Points to consider Look at the karyotype following this slide: –What is the modal chromosome number? –Is there a rearrangement present? –How many derivative chromosomes do you see? –Is this a balanced karyotype and if so, why?

69. Reciprocal Translocation 46,XX,t(2;17)(q21.3;q25.2)

70. Reciprocal Translocations: Points to consider Referring to the previous slide: –What is the modal chromosome number? 46 –Is there a rearrangement present? Yes, a reciprocal translocation. –How many derivative chromosomes do you see? Two. –Is this a balanced karyotype and if so, why? There is no apparent cytogenetic loss or gain of chromosome material, just a repositioning effect.

71. Robertsonian Translocation Joining of the long arm of two acrocentric chromosomes to form a single derivative chromosome loss of p arm material without phenotype effect modal chromosome number 45 in balanced carriers

72. Robertsonian Translocation n = 46n = 45 Fusion of two acrocentric chromosome occurs (A) to form a single derivative chromosome (B). With a balanced Robertsonian translocation, the modal number is reduced from 46 to 45 chromosomes.

73. Robertsonian Translocation: Points to consider Look at the karyotype following this slide: –What is the modal chromosome number? –Is there a rearrangement present? –How many derivative chromosomes do you see? –Is this a balanced karyotype and if so, why? –What material has been lost with this rearrangement, if any?

74. Robertsonian Translocation 45,XX,der(13q;14q)

75. Robertsonian Translocation: Points to consider (1) Referring to the previous slide: –What is the modal chromosome number? 45 –Is there a rearrangement present? Yes, two acrocentric chromosomes have joined at or near the centromere. –How many derivative chromosomes do you see? One, the acrocentric long arms have joined to form a single derivative chromosome. –Is this a balanced karyotype and if so, why? Yes, There is no loss of clinically relevant euchromatin with the formation of a single derivative chromosome.

76. Robertsonian Translocation: Points to consider (2) What material has been lost with this rearrangement, if any? The acrocentric p arms of chromosomes 13 and 14 have been lost with this rearrangement. Since the p arms contain ribosomal genes that are found on the short arms of other acrocentric chromosomes, there is no phenotype effect.

77. Reciprocal vs Robertsonian: Reciprocal -> 2 derivative chromosomes, 46 chromosomes total Robertsonian -> 1 derivative chromosome 45 = balanced 46 = unbalanced Either may or may not be inherited*

78. Consequences Of Structural Rearrangements Balanced carriers  phenotypic risks - low  reproductive risks - > background increased risk of miscarriage increased risk of offspring with –mental retardation –congenital anomalies WHY?

80. Anatomy of a Translocation During meiosis Gametes from Carrier  Gametes from Normal partner  Outcome Balanced Normal trisomy & monosomy trisomy & monosomy

81. Structural Aberrations Balanced rearrangements No visible loss or gain of genetic material: Inversions ( peri- and paracentric) a piece of chromosome flipped around and reinserted if it includes the centromere - pericentric if it excludes the centromere - paracentric These have slightly different genetic consequences as a result of meiotic pairing Can result in abnormal pregnancies and SAB May or may not be inherited*

82. Other forms of chromosome abnormalities deletions duplications insertions rings isochromosomes Deletions WHY??part of being human

88. Inversion (X)(p11.4q22) associated with Norrie Disease in a 4 generation family. Am J Med Genet 1993;45:577-580. Chromosome abnormalities can lead to gene location X-linked

89. Chromosome abnormalities can lead to gene location

90. Wolf-Hirshorn syndrome 4p- (Greek warrior helmet) Deletion syndrome

91. Cri du Chat syndrome 5p- Deletion syndrome

92. Prader-Willi syndrome Maternal / Paternal

93. Angelman syndrome – “happy puppet” – del 15q12 Maternal / Paternal

94. Sex chromosome abnormalities

100. 45,X Turner syndrome

101. 47,XXY Kleinfelter syndrome

103. Sex Determination 46,XY female SRY on Xp - XX male

104. Fragile X syndrome

105. Notice physical the similarities

106. Fragile X chromosomes vs. DNA Fragile X site

108. The