1. Changes in Chromosome Number
Chapter 3

2. Central Points Chromosomes are composed of DNA and proteins
Most humans have 46 chromosomes
Possible to test fetal chromosome number
Extra chromosomes affect fetus
Problems with genetic testing can result in lawsuits

3. Case A: Results Worry Pregnant Woman
Martha, age 41, is 18-weeks pregnant
Increased risk of chromosomal abnormalities
Amniocentesis recommended
Test results:
No Down syndrome
Fetus is XYY (Jacobs syndrome)

4. XYY Karyotype

5. 3.1 Chromosomes Thread-like structures in nucleus
Carry genetic information
Humans have 46
Parts
Centromere
p arm
q arm
Telomeres

6. p arm Centromere q arm Figure 3.1: Anatomy of a Chromosome.
The parts of a chromosome include the centromere and two arms (the short arm is the p arm, the long arm is the q arm).
Fig. 3-1, p. 43

7. Animation: How Cells Reproduce (chromosome structure and organization)

8. 3.2 Changes in Chromosome Number
Eggs and sperm are produced by meiosis
Begin with two copies of each chromosome (46)
Two divisions meiosis I and meiosis II
Homologous chromosome pairs separate
Produces haploid cells with one copy of each chromosome (23)

9. Meiosis: Produces Haploid Cells

10. Before cells begin meiosis, the chromosomes duplicate
Before cells begin meiosis, the chromosomes duplicate. As meiosis begins, chromosomes coil and shorten, and become visible in the microscope. Each chromosome has a matching partner and the two chromosomes may exchange parts (cross over) during this stage, called prophase I.
p. 44

11. to the centromere of each pair. This stage is called metaphase I.
The chromosome pairs line up along the middle of the cell, and spindle fibers attach
to the centromere of each pair. This stage is called metaphase I.
p. 44

12. Members of each homologous pair separate and move toward opposite sides of the cell. This stage is called anaphase I.
p. 44

13. The chromosomes reach opposite poles of the cell, and the nuclei begin to re-form. This stage is called telophase I. The cytoplasm divides, and two cells are formed. These cells have half the number of chromosomes of the original cells and are called haploid cells.
p. 44

14. MEIOSIS I
Before cells begin meiosis, the chromosomes duplicate. As meiosis begins, chromosomes coil and shorten, and become visible in the microscope. Each chromosome has a matching partner and the two chromosomes may exchange parts (cross over) during this stage, called prophase I.
The chromosome pairs line up along the middle of the cell, and spindle fibers attach to the centromere of each pair. This stage is called metaphase I.
Members of each homologous pair separate and move toward opposite sides of the cell. This stage is called anaphase I.
The chromosomes reach opposite poles of the cell, and the nuclei begin to re-form. This stage is called telophase I. The cytoplasm divides, and two cells are formed. These cells have half the number of chromosomes of the original cells and are called haploid cells.
Stepped Art
p. 44

15. Meiosis: Produces Haploid Cells

16. Two cells formed during meiosis I
Two cells formed during meiosis I. In prophase II, the chromosomes of these cells become coiled, and move toward the center of the cell.
p. 44

17. The 23 chromosomes in each cell attach to spindle fibers at their centromeres. This stage is called metaphase II.
p. 44

18. Each centromere divides, and the newly formed chromosomes (also called sister chromatids) move to opposite ends of the cell. This stage is called anaphase II.
p. 44

19. Finally, the chromosomes uncoil and the nuclear membrane re-forms
Finally, the chromosomes uncoil and the nuclear membrane re-forms. This stage is called telophase II. After the cytoplasm divides, the result is four cells, each with the haploid number of chromosomes. Meiosis is now completed.
p. 44

20. MEIOSIS II
Two cells formed during meiosis I. In prophase II, the chromosomes of these cells become coiled, and move toward the center of the cell.
The 23 chromosomes in each cell attach to spindle fibers at their centromeres. This stage is called metaphase II.
Each centromere divides, and the newly formed chromosomes (also called sister chromatids) move to opposite ends of the cell. This stage is called anaphase II.
Finally, the chromosomes uncoil and the nuclear membrane re-forms. This stage is called telophase II. After the cytoplasm divides, the result is four cells, each with the haploid number of chromosomes. Meiosis is now completed.
Stepped Art
p. 44

21. Events in Meiosis

22. Animation: Meiosis

23. Animation: Mitosis

24. Nondisjunction Chromosomes fail to separate
Results in gametes and zygote with an abnormal chromosome number
Aneuploidy is variations in chromosome number that involve one or more chromosomes
Most aneuploidy from errors in meiosis

25. Nondisjunction

26. Alignments at metaphase II
Chromosome
number in gametes:
Extra chromosome
(n + 1)
Extra chromosome
(n + 1)
Missing chromosome
(n – 1)
Missing chromosome
(n – 1)
Chromosomes
align at metaphase I
Figure 3.2: Nondisjunction.
Nondisjunction can cause abnormal chromosome numbers in gametes (eggs or sperm).
Nondisjunction
at anaphase I
Alignments at metaphase II
Anaphase II
Fig. 3-2, p. 45

27. Alignments at metaphase II
Chromosome
number in gametes:
Extra chromosome
(n + 1)
Missing chromosome
(n – 1)
Anaphase II
Alignments at metaphase II
Nondisjunction
at anaphase I
Chromosomes
align at metaphase I
Figure 3.2: Nondisjunction.
Nondisjunction can cause abnormal chromosome numbers in gametes (eggs or sperm).
Stepped Art
Fig. 3-2, p. 45

28. Aneuploidy Effects vary by chromosomal condition
Many cause early miscarriages
Leading cause of mental retardation

29. 3.3 ID of Chromosomal Abnormalities
Two tests:
Amniocentesis (> 16 weeks)
Collects amniotic fluid
Fetal cells grown and karyotype produced
Chorionic villus sampling (CVS) (10–12 weeks)
Rapidly dividing cells
Karyotype within few days

30. Amniocentesis

31. Fetal cells are removed from the solution
Removal of about 20 ml of amniotic fluid containing suspended cells that were sloughed off from the fetus
Biochemical analysis of the amniotic fluid after the fetal cells are separated out
Centrifugation
Fetal cells are removed from the solution
Analysis of fetal cells to determine sex
Cells are grown in an incubator
Karyotype analysis
p. 46

32. Fetal cells are removed from the solution
Removal of about 20 ml of amniotic fluid containing suspended cells that were sloughed off from the fetus
Biochemical analysis of the amniotic fluid after the fetal cells are separated out
Centrifugation
Fetal cells are removed from the solution
Analysis of fetal cells to determine sex
Cells are grown in an incubator
Karyotype analysis
Stepped Art
p. 46

33. Karyotype

34. Animation: Chromosomes and Human Inheritance (karyotype preparation)

35. Chorionic Villus Sampling (CVS)

36. Ultrasound to monitor procedure
Chorionic villi
Ultrasound to monitor procedure
Developing placenta
Developing fetus
Bladder
Uterus
Chorion
Catheter
Amniotic cavity
Rectum
p. 47

37. Amniocentesis Only Used in Certain Conditions
Risks for miscarriage; typically only done under one of following circumstances:
Mother > 35
History of child with chromosomal abnormalities
Parent has abnormal chromosomes
Mother carries a X-linked disorder
History of infertility or multiple miscarriages

38. Other Chromosomal Variations
Polyploidy: multiple sets of chromosomes
Euploid: normal two copies of each chromosome
Trisomy: three copies of one chromosome
Monosomy: only one copy of a chromosome
Structural changes: duplication, deletion, inversion, translocation

39. Structural Changes in Chromosomes

40. p. 47

41. One segment repeated three times
Normal chromosome
One segment repeated three times
p. 47

42. p. 47

43. Segment C deleted
p. 47

44. p. 47

45. Segments G, H, I become inverted
p. 47

46. p. 47

47. Chromosome A
Chromosome B
Translocation
p. 47

48. Animation: Chromosome abnormalities exercise

49. Animation: Meiosis and Sexual Reproduction (Meiosis I and II)

50. 3.4 Effects of Changes in Chromosomes
Vary by chromosome and type of variation
May cause birth defects or fetal death
Monosomy of any autosome is fatal
Only a few trisomies result in live births

51. Autosomal Trisomies

52. Autosomal Trisomies

53. Autosomal Trisomies

54. Trisomy 13: Patau Syndrome (47,+13)
1/15,000
Survival: 1–2 months
Facial, eye, finger, toe, brain, heart, and nervous system malformations

55. Patau Syndrome

56. Trisomy 13: Edwards Syndrome (47,+18)
1/11,000, 80% females
Survival: 2–4 months
Small, mental disabilities, clenched fists, heart, finger, and foot malformations
Die from heart failure or pneumonia

57. Edwards Syndrome

58. Trisomy 21: Down Syndrome (47,+21)
1/800 (changes with age of mother)
Survival up to age 50
Leading cause of childhood mental retardation and heart defects
Wide, flat skulls; eyelid folds; large tongues; physical, mental, development retardation
May live rich, productive lives

59. Down Syndrome

60. Leading Risk Factor for Trisomy
Maternal age
Unknown why, older eggs increase risk of nondisjunction
Eggs held in meiosis I from birth to ovulation
Possible changes in maternal selection

61. Maternal Age and Down Syndrome

62. Aneuploidy and Sex Chromosomes
More common than in autosomes
Turner syndrome (45,X): monosomy of X chromosome
Klinefelter syndrome (47,XXY)
Jacobs syndrome (47,XYY)

63. Sex Chromosome Trisomies

64. Sex Chromosome Trisomies

65. Sex Chromosome Trisomies

66. Turner Syndrome (45,X) Survival to adulthood
Female, short, wide-chested, undeveloped ovaries, possible narrowing of aorta
Normal intelligence
1/10,000 female births, 95–99% of 45,X conceptions die before birth

67. Turner Syndrome

68. Klinefelter Syndrome (47,XXY)
Survival to adulthood
Male
Features do not develop until puberty, usually sterile, may have learning disabilities
1/1,000 males

69. Klinefelter Syndrome

70. XYY or Jacobs Syndrome (47,XYY)
Survival to adulthood
Average height, thin, personality disorders, some form of mental disabilities, and adolescent acne
Some may have very mild symptoms
1/1,000 male births

71. XYY Syndrome

72. 3.5 Ways to Evaluate Risks
Genetic counselors are part of the health care team
In nondirective way, they assist understanding of:
Risks
Diagnosis
Progression
Possible treatments
Management of disorder
Possible recurrence

73. Counseling Recommendations (1)
Pregnant women or those who are planning pregnancy
Women > age 35
Couples with a child with:
Mental retardation
A genetic disorder
A birth defect

74. Counseling Recommendations (2)
Couples from certain ethic groups
Couples that are closely related
Individuals with jobs, lifestyles, or medical history that may pose a risk to a pregnancy
Women who have had two or more miscarriages or babies who died in infancy

75. Genetic Counseling Most see a genetic counselor: Counselor
After a prenatal test;
After the birth of a child; or
To determine their risk
Counselor
Constructs a detailed family history and pedigree
Shares information that allows an individual or a couple to make informed decisions

76. Case A Questions Child is XYY: What are the best options?
Would the options change if the child had a different condition?
Who should know?
See the textbook for further questions on this case

77. Case B: Test Results Worry Doctor
31-year-old woman gave birth to a child with serious abnormalities
Sued doctor for not performing amniocentesis
What legal issues should concern the doctor and what should she do?
See the textbook for further questions on this case

78. Future of Genetic Counseling
Human Genome Project (HGP) changed medical care and genetic testing
Genetic counselor will become more important
Evaluate reproductive risks and other conditions
Allow at-risk individuals to make informed choices about lifestyle, children, and medical care

79. 3.6 Legal and Ethical Issues
Wrongful-birth suit
Wrongful-life suit
Based on:
Could a diagnosis of this condition have been made in time to have an abortion?
Was the condition serious enough that a reasonable person would have had an abortion?

80. Wrongful-Birth and Wrongful-Life Cases

81. Issues with Wrongful-Birth and Wrongful-Life Suits
Wrongful-birth suit (most states allow):
Roe v. Wade gave a woman an alternative to birth
Doctors have extensive medical malpractice insurance
Wrongful-life suits (only 5 states allow):
Courts uncomfortable declaring someone should never have been born

82. XYY Individuals (Jacobs Syndrome)
Early studies linking XYY with aggressive/ criminal behavior no longer supported by research
Should parents and or child know the condition?
What should the doctor do?

83. Spotlight on Law: Becker v. Schwartz
Becker, age 37, was not informed about amniocentesis
Child born with Down syndrome, parents sued doctor for “wrongful life”
Parents won $2,500 and gave baby up for adoption
What is your opinion on this case?