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

39
(No Transcript)