2/13/16
BIOLOGY 207 - Dr.Locke
Lecture#18 - Chromosome Rearrangements
Required readings and problems:
Reading: Open Genetics, Chapter 5
Problems: Chapter 5
Optional
Griffiths (2008) 9th Ed. Readings: pp 572-589
Problems: 9th Ed. Ch. 16: 22-28
Campbell (2008) 8th Ed. Readings: Concept 14.4
Concepts:
How are chromosome rearrangements mutations?
1. Chromosomes can undergo physical rearrangements of their DNA, which include
deletions, duplications, inversions, and/or translocations of DNA segments.
2. Rearranged chromosomes may pair improperly at meiosis and alter the distribution
of chromosomes thereby affecting fertility.
3. Rearrangements can break genes and produce unbalanced gametes (and therefore
unbalanced progeny).
Biol207 Dr. Locke’s section
Lecture#18
Fall'11
page 1
2/13/16
Chromosome Rearrangements
They involve breaks in the DNA duplex -- both strands -- followed by the rejoining of
the broken ends.
The result is a reorganized chromosome that usually can be transmitted to subsequent
generations.
It happens ONCE (the mutational event) and is then passed on (inherited).
If not repaired they are lost/gained:
1- the cell usually dies because it is unbalanced
2- abnormal phenotype
3- importance in medicine - cancer
4- importance in evolution – new source of genes for selection
Relationship of a break to a gene
Biol207 Dr. Locke’s section
Lecture#18
Fall'11
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Example of a normal chromosome :
abcdef-o-ghij (with -o- = centromere)
Deletions
 - the loss of a region of DNA from a chromosome
 abcdef-o-ghij
 abef-o-ghij where the cd region has been deleted.
Duplications
 - the gain of a region of DNA
 abcdef-o-ghij if region cd is duplicated it gives
 abcdcdef-o-ghij
Inversions
 - involve the inversion of a segment of a chromosome
 abcdef-o-ghij - with breaks between c and d as well as h and i gives
 abchg-o-fedij
Translocations
 - involve breaks on non-homologous chromosomes with an exchange of parts
 abcdef-o-ghij and qrst-o-uvw to give
 abcdef-o-gvw and qrst-o-uhij
Biol207 Dr. Locke’s section
Lecture#18
Fall'11
page 3
2/13/16
Deletions
There are two types of deletions:
 interstitial - which have two breaks within the chromosome and the region
between them is lost
 terminal - which involves one break and the segment distal to the break, including
the telomere, is lost
Pseudo-dominance
1- Deletions remove many genes consecutively positioned along a chromosome.
2- Thus recessive alleles within this hemizygous region will be expressed.
3- The recessive is said to be pseudo-dominant when the homologue is paired with
the deletion.
Biol207 Dr. Locke’s section
Lecture#18
Fall'11
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2/13/16
Deletions can map the location of genes on a cytogenetic map
Deletion loop-absence of a chromosome segment when homologous chromosomes
pair (at meiosis)
The location of the deletion maps genes cytogenetically.
Thus one can compare the locations of genes on the genetic map (map units -- which
represent recombination frequencies) and the cytogenetic map (which represents
physical distances --> sequence).
To identify a deletion mutation: (recognized by several characteristics)
1) Pseudo dominance - involves several adjacent loci
2) Cytologically - deletion loops
3) Usually recessive-lethal - lost essential genes
4) Lack of reverse mutation - cannot revert absence of DNA
Biol207 Dr. Locke’s section
Lecture#18
Fall'11
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2/13/16
Duplications
Two major forms:
 Tandem - abcde cdef-o-ghij
- duplication of a segment is direct
 Reverse (inverse) - abcde edcf-o-ghij
- duplicated segment is reversed
Result is extra genes - those within the duplicated region
At Meiosis the duplicated segment is able to pair with homologous region on the same
chromosome as well as on the homologue – Fig
Unstable:
ab cde cdef-o-ghij
2 copies
abcdecdecdef-o-ghij 3 copies
X
->
abcde cde f-o-ghij
2 copies
abcdef-o-ghij
1 copy
Evolution:
- increases the number of genes -> new genetic material available for mutation,
divergence, and selection (e.g. globin genes)
Duplications can be recognized by:
1) Cytologically visible - duplication loop
2) Usually not recessive lethal - duplication of genes
3) Can revert and at relatively high rate (unequal crossing over)
Biol207 Dr. Locke’s section
Lecture#18
Fall'11
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2/13/16
Inversions – no gain or loss – just rearrangement
Inversions have two major types:
(depend upon the positions of the breakpoints in relation to the centromere)
 Paracentric Inversions have breaks on the same chromosome arms. (| = break)
 ab|cde|f-o-ghij -> ab edc f-o-ghij
 Pericentric Inversions have breaks on different chromosome arms
 ab|cdef-o-gh|ij -> ab hg-o-fedc ij
Biol207 Dr. Locke’s section
Lecture#18
Fall'11
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2/13/16
Pairing at meiosis:
Paracentric inversion - events
Fig
When an inversion homolog pairs with a normal sequence homologue
-> an inversion loop results.
A single cross over within the loop results in the production of an acentric fragment
(which is lost) and deletion products.
The deletion products, if incorporated into a zygote, are usually lethal.
Only two of the four gametes would produce viable gametes,
both of which are parental in organization: one normal + one inversion.
Consequences:
1) "recombinants" (vs. parentals) will be reduced in frequency
- recombinant chromosomes are inviable (lethal).
2) Genetic markers within the loop will have an RF of ~ 0 - absolute linkage.
The only way a recombinant can be recovered is if there is a second cross over
involving the same chromatids of the first cross over event.
3) Inversions inhibit the actual pairing of regions near, or in-between the break points,
so crossing-over cannot occur.
Biol207 Dr. Locke’s section
Lecture#18
Fall'11
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2/13/16
Pericentric Inversions
Fig
The effects are much the same.
The actual products are different (no acentric fragments).
Note for both types of inversions:
If both homologues are equivalent (ie. homozygous inversion), then no inversion loop
is formed and both chromosomes pair.
No abnormal products are formed by crossover events. The only consequence is a
linkage map that has an inverted gene order.
Biol207 Dr. Locke’s section
Lecture#18
Fall'11
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2/13/16
Translocations - Reciprocal translocation
 There are consequences for the pairing
at meiosis when heterozygous with
normal chromosomes.
 Two normal homologues (N1, N2). Two
translocation chromosomes (T1, T2).
 Homologous regions of each
chromosome synapse and result is a
pairing configuration that involves:
2 pairs of homologues
4 chromosomes
8 chromatids
 Such a configuration can have several types of segregation depending upon how it
lines up on the equatorial plate
 Homologous paired centromeres disjoin.
 There are two common patterns of disjunction.
Biol207 Dr. Locke’s section
Lecture#18
Fall'11
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2/13/16
Adjacent-1 segregation
 T1 with N2 (Top two)
 N1 with T2 (Bottom two)
 The result is unbalanced gametes:
duplication/deficient
 Unbalanced gametes are inviable.
 It is called adjacent because adjacent centromeres
move to the same poles.
Alternate segregation
 It is called alternate because alternate centromeres
move to the same pole with the result that:
 T1 with T2 and N1 with N2
 Both products (and all 4 gametes) are balanced and
viable.
Note: Adjacent-1 and Alternate happen equally
frequently therefore only 50% of the total number of
products are viable.
Biol207 Dr. Locke’s section
Lecture#18
Fall'11
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Consequences for translocation bearing individuals
(heterozygotes).
1 - Inviable gametes are meiotic products that are:
- capable of forming sex cells
- but when joining normal gametes
-> unable to form a viable zygote (it is due to the unbalanced gamete).
2 - Translocations (and Inversions) result in reduced fertility due to inviable gametes.
3 - Only semi-sterile.
Note - Inversions (and to a lesser extent, Translocations) also affect the linkage
between marker loci on the chromosomes involved.
- recombinants die and thus the apparent genetic distance is reduced
Biol207 Dr. Locke’s section
Lecture#18
Fall'11
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