1. Chromosome Mutation Relocation of Genetic Material
Mutations change:
1) Amount of genetic material
2) Location of genetic material
Specific Types of Changes:
- Deletions and Duplications
- Change (up or down) in chromosome # (individual chromosomes or whole sets of chromosomes
- Translocations (balanced or unbalanced)
- Inversions (pericentric or paracentric)
Relocation of Genetic Material
how do chromosome rearrangements occur?
how can we detect them
what are their genetic and phenotypic consequences?

2. Mechanisms of Chromosome Rearrangements
Breakage and rejoining (can be between genes or within one or more genes)
Breakage by DNA damage (e.g. irradiation), or errors in mitosis, or after chromosome fusions which create dicentric chromosomes (breaks during next mitosis)
Rejoining during attempts to repair damage
Position and number of breaks and the process of rejoining determines the type of rearrangement
Deletion, Deletion + duplication, inversion, reciprocal translocation, non-reciprocal translocation
Individuals carrying deletion + duplication, reciprocal translocation, or non-reciprocal translocation, can produce gametes with unbalanced rearrangements (later)
- balanced rearrangements = no loss or gain of genetic material
- unbalanced rearrangements = gain or loss or both
Translocation chromosomes containing more than 1 centromere typically are unstable (dicentric chromosomes) and undergo repeated anaphase bridge-breakage-fusion cycles (later)
Chromosome derivative containing no centromere are usually lost (sometimes a new centromere forms...

3. Mechanisms of Chromosome Rearrangements
Mechanism: physical or chemical breakage and rejoining
Rejoining wrong ends together:
- DNA is folded
- folds bring different segments together

4. Mechanisms of Chromosome Rearrangements
Unequal homologous recombination (unequal crossovers) between repetitive DNA on same chromosome, homologous chromosomes, non-homologous chromosomes
Repeats can be the highly repetitive DNA (Transposon or genes) or large genome duplications called “segmental duplications”
- large, relatively recent duplications of non-repetitive DNA
Same chromosome = deletions; which piece is lost depends on where centromere is relative to the repeats. Or, = inversion
- depends on whether repeats are direct or inverted
Homologous chromosomes = deletion duplication
Non-homologous chromosomes = reciprocal translocations

5. Inversion loop at meiosis in an Inversion Heterozygotes

6. Inversion loop at meiosis in an Inversion Heterozygotes

7. Generation of acentric and dicentric chromosomes by meiotic recombination in inversion heterozygotes

8. Decrease in RF in Paracentric Inversion Heterozygotes
50 cM
10 cM
30 cM in WT
10 cM
u v w x y
~ fewer
crossovers
< 10 cM
~ no crossovers
~ 0 cM
< 20 cM
u x w v y
Paracentric inversion

9. Pericentric Inversions
Detect by inversion loops and reduction in RF in crosses
Recombination within loop produces duplication + deletion gametes
Essentially complete linkage within the duplication, increase in linkage for genes at the borders of the duplication…

10. Translocation Heterozygotes allow detection of translocations cytologically and genetically
Quadravalent in Cross-shape forms at meiosis
Segregation patterns produce either viable or duplication + deletion gametes
here, ½ of gametes are duplication deletion independently of recombination
semisterility
Compare/contrast consequences of inversions to translocations in crosses involving heterozygotes
- reduction in number of viable progeny
- which progeny genotypes are missing
- what if the inversion heterozygote is only heterozygous for markers within the inversion?

11. Application of Inversion or Translocation Rearrangements
Disease gene mapping – example NF1 gene responsible for neurofibromatosis
- used rearrangement breakpoint mapping
Create strains carrying duplication or deletions
Small inversions or translocations can result in viable progeny
Balancer Chromosomes in Drosophila
Prevent recombination anywhere on a chromosome in a inversion heterozygote

12. Deletions Deletions can be small – single gene – or larger – multigene
- single gene deletions create null alleles
- best for deducing function of the gene from the mutant phenotype
multigene deletions can be recessive or dominant lethal dependent on affect on gene dosage
recessive multigene deletions can reveal presence of recessive point mutations in that region (see deletion mapping, later)
Detect deletions cytologically – deletion loops in meiosis or polytenes
Detect recessive deletions phenotypically – recessive point mutations in that region will all be expressed when combined with the deletion
Use of deletions in gene mapping…

13. Drosophila Polytene Chromosomes allow deletion loops to be visualized

14. Using multigene deletions for mapping the location of point mutants
pn mutation is expressed in progeny from cross of pn mutant with
Fa mutation is expressed in progeny from all crosses except those involving and
Determine results for w and rst for yourself – which crosses produce progeny expressing these recessive phenotypes?

15. Human diseases associated with deletions
1% of institutionalized mental retardation patients
Characteristic facial appearance, cry in newborns, microcephaly, other physically apparent and physiological features
Due to deletion of genes associated with 5p15.2 through 5p15.3
Most are spontaneous deletions during gametogenesis
Heritable form from heterozygous parents carrying a small translocation involving the end of chromosome 5
- adjacent 1 segregation leads duplication or deletion of this region

16. Conceptions involving chromosome abnormalities are relatively common
7.5 up to 15% of all
Conceptions!
Conceptions involving chromosome abnormalities are relatively common