24.3: Changes in Chromosome Number

1.Humans typically have

  1. 22 pairs of autosomal chromosomes
  2. 1 pair of sex chromosomes
  3. 46 total chromosomes
  4. Different numbers usually caused by Nondisjunction during meiosis
  5. Both members of a homologous pair end up in one gamete
  6. Any change to this number causes disorders
  7. Trisomy: having 1 extra chromosome for one pair
  8. Monosomy: having only 1 copy of a chromosome instead of a pair
  9. Chances of survival of offspring are greatly diminished from the normal 23 pairs
  10. Chance of survival increases if trisomy/monosomy occurs with sex chromosomes
  1. Sex Chromosome Trisomy/Monosomy
  2. Normal Female: XX
  3. Normal Male: XY
  4. Trisomy/Monosomy of Sex Chromosomes
  5. X Chromosome
  6. Nondisjunction during oogenesis typical, but can be during spermatogenesis (mother donates X and father donates X or Y)
  7. Typically, one of the X chromosomes in a normal (XX) female becomes darkly stained mass called Barr Body which is an inactive chromosome in normal female (XX)
  8. Cells of normal females (XX) function with only one active X chromosome
  9. Likely why a female with Turner Syndrome can survive (X)
  10. All extra X’s beyond 2 also become Barr Bodies, which is likely why extra X chromosomes also pose less risk of fatality and are seen relatively frequently
  11. Y Chromosome
  12. Caused by nondisjunction during spermatogenesis
  13. Viewing Chromosomes
  14. Karyotype:
  15. visual display of chromosomes arranged by size, shape, and in homologous pairs
  16. Trisomy/monosomy can be viewed
  17. Methods of Karyotyping Fetus:
  18. Amniocentesis:
  19. amniotic fluid is removed with a long needle
  20. Increases risk of spontaneous abortion (miscarriage) by 0.25-0.5%
  21. Other tests for genetic diseases can also be done
  22. Chorionic Villus Sampling:
  23. CVS
  24. Chorionic cells obtained in region where placenta will develop
  25. Suction tube inserted into vagina into the uterus
  26. Ultrasound used to guide technician
  27. Faster results than amniocentesis, but increased risk of spontaneous abortion (0.5-1.0%)
  28. Syndromes from abnormal Chromosome numbers:

Syndrome / Sex / Chromosomes / Ch. Number / Frequency
Spontaneous Abortions / Live Births
Down / M or F / Trisomy 21 / 47 / 1/40 / 1/733
Poly-X / F / XXX (or XXXX) / 47 or 48 / 0 / 1/1,500
Klinefelter / M / XXY (or XXXY) / 47 or 48 / 1/300 / 1/800
Jacobs / M / XYY / 47 / ?? / 1/1,000
Turner / F / X / 45 / 1/18 / 1/2,500
  1. Down Syndrome
  2. Most common trisomy among humans
  3. Only autosomal trisomy that has reasonable survival after birth
  4. Probably b/c chromosome 21 is one of the smallest
  5. Usually from nondisjunction during oogenesis (23% from spermatogenesis)
  6. Risk increases with age of mother
  7. Short stature, eyelid fold, flat face, stubby fingers, wide gap b/t first and second toes, large fissured tongue, round head, palm crease, mild to severe mental impairment
  8. Increased risk for leukemia, cataracts, accelerated aging
  9. Life expectancy severely lower than normal population
  10. Turner Syndrome (X female)
  11. Short, may have malformed features (e.g. webbed neck, high palate, small jaw), congenital heart disease, kidney defects
  12. Most will not undergo puberty or menstruate w/o sex hormone replacement therapy
  13. Pregnancy possible through in vitro w/ donor eggs
  14. May have some nonverbal learning disabilities
  15. Klinefelter Syndrome (XXY or XXXY male)
  16. Subtle symptoms so that only 25% of affected are diagnosed until after age 15
  17. Will need assisted reproduction to father children
  18. Poly-X Females (XXX or XXXX female)
  19. XXX
  20. No distinctive phenotype
  21. May have menstrual/fertility problems
  22. XXXX
  23. Tall and more likely to be mentally impaired
  24. Jacobs Syndrome (XYY male)
  25. Taller than average
  26. Bad acne
  27. Tend to have speech and reading problems
  1. Screening vs. Diagnostic Testing
  2. Screening tests are preliminary and indicate probabilities of certain syndromes
  3. Ultrasounds: Can look for certain physical features that show probability of Down’s Syndrome (A specialultrasound, called anuchaltranslucency screening, measures your baby's nasal bone as well as the fluid at the back of your baby's neck. ... The combined result of the blood tests and theultrasoundgives you a sense of your baby's risk.)
  4. Blood tests: Looks for elevated levels of certain hormones in mother’s blood that may indicate an abnormality
  5. Diagnostic tests test directly for a syndrome using karyotyping
  6. Traditionally done through an amniocentesis or CVS sampling
  7. An amniocentesis is covered by the government in Canada
  8. Non-Invasive Diagnostic Testing
  9. Uses a sample of mother’s blood and can be done as early as 10 weeks into pregnancy
  10. The “Harmony” test is a non-invasive diagnostic test that tests for common trisomies
  11. Cost is approximately $500 in Canada
  12. 99% accurate diagnosis of Down’s Syndrome