1. Chapter 9 – Chromosomal Variation

2. Chromosome Morphology
Metacentric
Centromere is centrally located; arms equal length
“p” and “q” – “p” is smaller when there is a size difference
Submetacentric
Centromere is off center
Acrocentric
Centromere is close to one end
p arm has satellites (knobs on stalks)
Telocentric
Centromere is at one end
Not present in humans

3. Karyotype Complete set of chromosomes arranged in homologous pairs
Sample is from an actively dividing cell
Chemical inhibits spindle assembly formation
Cell can not complete mitosis
Hypotonic solution swells cell
Allows chromosomes to spread out
Dropped on slide and stained

4. Staining G banding C banding R banding Q banding
Giemsa stain; most common
Stains A-T rich regions
C banding
Stains centromeric heterochromatin and portions of chromosomes with large sections of heterochromatin
1, 9, 16, Y
R banding
Stains G-C rich regions
Gives opposite banding pattern of G banding
Q banding
UV light is used
Same pattern as G banding

5. Staining

6. Types of chromosome mutations
Chromosomal rearrangement
Structure is altered
Aneuploidy
Abnormal number of chromosomes
Missing one or more/having one or more extra
Polyploidy
1 or more additional sets of chromosomes

7. Chromosome rearrangements
4 types
Duplications
Deletions
Inversions
Translocations

8. Duplications Section of chromosome is doubled Tandem Displaced Reverse
Repeated segment is right after the original
Displaced
Repeated segment is located elsewhere on chromosome, or on a different chromosome
Reverse
Sequence is inverted from the original sequence

9. Duplications Heterozygotes
During paring of homologous chromosomes, duplicated region loops out
Offspring receive two copies of involved genes from parent with duplication, and a third copy of the other parent
Partial trisomy for all involved genes
Alters gene dosage

10. Gene dosage

11. Deletions Loss of a portion of chromosome
Large deletions can be seen cytogenetically; microdeletions by FISH
If the deleted region includes the centromere, entire chromosome will be lost
Usually lethal in homozygous form
Heterozygotes
Normal chromosome must loop out during pairing
Partial monosomy for all involved genes

12. Deletions - heterozygotes
Affects gene dosage
Pseudodominance
Expression of mutant/recessive phenotype due to loss of normal/dominant copy
Haploinsufficiency
Both copies of the gene are needed to manufacture adequate amount of gene product
One gene doesn’t produce enough for a normal phenotype

13. Inversions Two breaks in chromosome, then flipped and reinserted
Paracentric inversion
Both breaks occur in one arm
Pericentric inversion
Breaks on both arms; centromere is involved
Can change morphology by altering centromere position
Effects
Disruption of a gene – no functional product
Position effect
Change in gene position can affect gene expression

14. Inversion loops Chromosomes have to loop when pairing
Paracentric inversion loops
If crossing over occurs within loop:
Creates a dicentric chromosome and an acentric chromosome
Acentric is lost
Dicentric forms a dicentric bridge, and breaks
Nonviable recombinant gametes

15. Paracentric inversion loop

16. Inversion loops Pericentric inversion loops
Crossing over within loop creates recombinant chromosomes with duplications and deletions
nonviable

17. Pericentric inversion loops

18. Translocations
Rearranges genetic material to another part of the same chromosome; or nonhomologous chromosome
Nonreciprocal
Segment moves from one chromosome to another
Reciprocal
Exchange between two chromosomes
Effects
Loss of gene function – break
Position effect
Creation of a fusion/abnormal protein

19. Robertsonian translocation
Between two acrocentric chromosomes
13, 14, 15, 21, 22
2 q arms are joined at a common centromere
Forms a metacentric chromosome if two chromosomes are same size
Small fragment is usually lost
Tends to be acentric

20. Translocations
Translocated chromosome is named after the chromosome that is the origin of the centromere
Heterozygotes have one normal copy of a chromosome, and one translocated one
During meiosis, all 4 chromosomes will associate
Can segregate 1 of 3 ways

21. Translocation segregation
Alternate
Both normals go to one pole; both translocated go to the other
Balanced; viable
Adjacent 1
Each pole gets one normal, and the opposite translocated
Partial monosomies/partial trisomies
inviable
Adjacent 2
Each pole gets both the normal and translocated of the same chromosome
Inviable; rare

22. Translocation segregation

23. Fragile sites
Under certain conditions/culturing techniques, chromosomes develop breaks/restrictions at particular locations
Now routinely tested for by FISH analysis

24. Aneuploidy Abnormal number of chromosomes Types Caused by:
Loss of chromosome during cell division; random error or loss of centromere; nondisjunction
Robertsonian translocation
Types
Nullisomy 2n – 2 – missing both members of a homologous pair
Monosomy 2n – 1 – missing one chromosome
Trisomy 2n + 1 – one extra chromosome
Tetrasomy – 2n + 2 – two extra chromosomes of the same type/homologous

25. Aneuploidy Alters phenotype dramatically Down syndrome
Often lethal if constitutional
Can see elaborate abnormalities in tumor cells
X inactivation in mammals takes care of extra Xs, so not as severe
Down syndrome
Primary
3 free copies of #21
Familial
Extra copy due to translocation
Can be involved in Robertsonian translocation
Parent can have 45 chromosomes, but have normal phenotype since all genetic material is present

27. Uniparental Disomy
Both chromosomes of a homologous pair from the same parent
Probably originated from a trisomy
One chromosome is lost early in development
Recessive diseases
One carrier parent and one normal parent can have an affected child

28. Mosaicism
Nondisjunction in later development can cause “patchiness” – normal cells and abnormal cells
Approximately 50% of Turner syndrome can be mosaics
45, XO/46, XX

29. Polyploidy Extra sets of chromosomes
Triploid – 3n; tetraploid – 4n
Common in plants – more tolerant of extra sets of chromosomes
Autopolyploidy
Extra set is from same species
Error in cell division
Extra chromosome caused pairing problems; especially with odd numbers
3n usually sterile; produce small seeds
Bananas; “seedless” watermelon

31. Polyploidy Allopolyploidy Hybridization between two species
AABBCC x GGHHII
F1 generation ABCGHI – not homologous
Gametes are inviable, but may be able to reproduce asexually
Nondisjunction error can lead 2x, which could then reproduce sexually