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

3. 3.1 Chromosomes Thread-like structures in nucleus
Carry genetic information
Humans have 46
Parts
Centromere
p arm
q arm
Telomeres

5. 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)

6. Meiosis: Produces Haploid Cells

7. Meiosis: Produces Haploid Cells

8. Animation: Meiosis

9. 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

10. Meiosis: The Creations of Gametes

11. Non-Disjunction During Meiosis
Non-disjunction in Meiosis 1
Non-disjunction in Meiosis 2

12. Monosomy zygote
Trisomy zygote

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

14. 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

15. 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

16. 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

17. Chorionic Villus Sampling (CVS)

18. Karyotype

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

20. Non-Invasive Prenatal Diagnosis
In 1997 it was determined the “cell-free” fetal DNA is found in maternal plasma
Has been used to determine the sex and blood group of the fetus
Harder to detect fetal chromosomal aneuploidies, because fetal DNA is only 3% of cell-free DNA in maternal plasma

21. Other Chromosomal Variations
Haploid: one copy of each chromosome
Diploid: normal two copies of each chromosome
Polyploidy: multiple sets of chromosomes
Aneuploid: A variation in chromosome number, but not involving all of the chromosomes
Trisomy: three copies of one chromosome
Monosomy: only one copy of a chromosome
Structural changes: duplication, deletion, inversion, translocation

22. Duplication

23. Deletion

24. Karyotype of Deletion on Chromosome 16

25. Inversion

26. Translocation

27. Translocation Karyotype

28. 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

29. Patau Syndrome

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

31. Edwards Syndrome

32. Trisomy 18: 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

33. Down Syndrome

34. 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; large tongues; physical, mental, development retardation

35. Maternal Age and Down Syndrome

36. 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)

37. Turner Syndrome

38. 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

39. Klinefelter Syndrome

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

41. XYY Syndrome

42. 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

43. 3.5 Ways to Evaluate Risks
Genetic counselors are part of the health care team
They assist understanding of:
Risks
Diagnosis
Progression
Possible treatments
Management of disorder
Possible recurrence

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

45. Counseling Recommendations (2)
Couples from certain ethnic 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

46. 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

47. 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