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
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 After puberty (each month)
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