Chromosomes

1. Chromosomes

2. Cytogenetics • A subdiscipline within genetics • Focuses on chromosome variations • Abnormal number of copies of genes or chromosomes can lead to genetic abnormalities • Human genome sequence information is used to identify genes that contribute to the chromosome-related syndromes

3. Portrait of a Chromosome • Primarily DNA and protein • Described by size and shape • Heterochromatin (dark) • Euchromatin (light) • Contains: • Telomeres • Origin of replication sites • Centromere

4. Chromosomes • Heterochromatin is darkly staining, contains mostly repetitive DNA • Euchromatin contains more protein encoding genes • Telomeres are chromosome tips composed of many repeats of TTAGGG and shorten with each cell division • Centromere is the largest constriction of the chromosome and where spindle fibers attach

5. Centromere Position • At tip telocentric • Close to end  acrocentric • Displaced from center  submetacentric • Long arm q • Short arm p • At midpoint metacentric

6. Karyotype • Chromosomal chart • Chromosomes arranged by size and structure • Arranged by largest to smallest

7. Visualizing Chromosomes Fetal tissue: amniocentesis chorionic villi sampling fetal cell sorting Adult tissue: blood (white blood cells) cheek swab (buccal cells) skin cells tissue biopsy

8. Amniocentesis Figure 13.5a

9. Chorionic Villi Sampling Figure 13.5b

10. Fetal Cell Sorting Figure 13.5c

11. FISHing • Fluorescence in situ hybridization • in situ =in tissue • in vivo =in living organism • in vitro =in a dish • Uses a fluorescent probe to detect specific sequences of DNA

12. Chromosomal Abnormalities

13. Abnormal Chromosome # -Polyploidy • Polyploidy • An entire extra set of chromosome • Example: Triploidy • One egg fertilized by 2 sperm OR • A diploid egg fertilized by one sperm • A diploid sperm fertilizes an egg

14. Abnormal Chromosome # -Aneuploidy • Missing a single chromosome (monosomy) • OR - • Having one extra chromosome (trisomy) • Euploid =“good set” • Aneuploid =“not good set” • Caused by nondisjunction during meiosis

15. Nondisjunction at Meiosis I

16. Nondisjunction at Meiosis II

17. Nondisjunction at Mitosis • Results in a mosaic • Some cell populations are affected while others are not • Severity of symptoms depends on how early in development the nondisjunction occurs.

18. Autosomal Aneuploids • Usually lethal • Those that survive often have mental retardation • Most common for chromosomes 13, 18, and 21. Why?

19. Trisomy 21 • October is Down Syndrome Awareness Month!

20. Table 13.6

21. Figure 13.7

22. Oogenesis Before birth Arrested in Prophase I After puberty (each month) Arrested in Metaphase II Upon fertilization

23. Trisomy 18 • Edward syndrome • Severe physical and mental disabilities • Development stops at the 6 month level • Oddly clenched fists • Low-set ears • Small mouth • Unusual or absent fingerprints • Liver and heart problems

24. Trisomy 13 • Patau syndrome • Fusion of the eyes or a small or absent eye • Cleft lip and palate • Extra fingers and toes • Mental retardation

25. Sex Chromosome Aneuploidy

26. Sex Chromosome Aneuploids: Female • Turner syndrome (XO) • Delayed puberty • 99% are not born • Infertile • Triplo-X (XXX) • Tall stature • Menstrual abnormalities • All but 1 X is inactivated

27. Sex Chromosome Aneuploids: Male • Klinefelter Syndrome (XXY) • Sexually underdeveloped • Small testes • Sparse facial and pubic hair • Long arms and legs and big feet and hands • May develop breast tissue • Often infertile

28. Sex Chromosome Aneuploids: Male • XXYY Syndrome • Slightly delayed childhood development • Behavioral problems • ADD, OCD, and learning disabilities • Leg ulcers due to poor circulation • Sexual development is delayed • Testes do not descend • Infertile • Abnormal (YY) sperm AND abnormal (XX) egg

29. Sex Chromosome Aneuploids: Male • Jacobs Syndrome (XYY) • 1/1000 males has an extra Y • 96% of XYY males are normal • Tall height and acne • Criminals with chromosomal abnormalities tend to have XYY

30. Abnormal Chromosome Structure • Deletion =missing genetic material • Can range in size (the more genes deleted, the worse the phenotype) • Duplication =a region of the chromosome where genes are repeated • Inversion =the DNA sequence in a region of the chromosome is inverted • Translocation =a piece of the chromosome is moved to another chromosome

31. Translocation • Nonhomologous chromosome exchange segments Two major types: • Robertsonian translocation • Two nonhomologous acrocentric chromosomes break at the centromere and long arms fuse. The short arms are often lost. • 5% of Down syndrome results from a Robertsonian translocation between chr 21 and chr 14. • Reciprocal translocation • Two nonhomologous chromosomes exchange a portion of their chromosome arms.

32. Segregation of a Robertsonian Translocation

33. Reciprocal Translocation • Exchange of material from one chromosome arm to another • Some individuals carry a translocation but are not missing any genetic material unless a translocation breakpoint interrupts a gene

34. Inversions • Inverted chromosomes have a region flipped in orientation • 5-10% cause health problems probably due to disruption of genes at the breakpoints • Inversions may impact meiotic segregation • Two types of inversions occur: • Paracentric • inverted region does NOT include centromere • Pericentric • inverted region includes centromere

35. Segregation of a Paracentric Inversion Figure 13.21

36. Segregation of a Pericentric Inversion Figure 13.22

37. Isochromosomes • Chromosomes with identical arms • Form when centromeres divide along the incorrect plane during meiosis Figure 13.23

38. Ring Chromosomes • Chromosomes shaped like a ring • Occur in 1 in 25,000 conceptions • May arise when telomeres are lost and sticky chromosome end fuse • Radiation exposure