Download Chromosome Rearrangements Concepts: Chromosome

Lecture 21; 2007
Biology 207; Section B2; Good
Chromosome Rearrangements
Readings: Griffiths et al:
8th Edition: pp. 496-508, 7th Edition: Ch. 17 pp 523-554
Assigned Problems:
8th Ch. 15: 22-28, 40-43, 47, 7th Ch. 17: 1-23
Concepts:
How can chromosomes be altered?
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).
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.
If not repaired they are lost and the cell usually dies because it is unbalanced.
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
Deletions
There are two types of deletions:
interstitial - which have two breaks within the chromosome and the region between
there is lost
terminal - which involves one break and the segment distal to the break, including the
telomere, is lost
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Lecture 21; 2007
Biology 207; Section B2; Good
Pseudo-dominance
Deletions remove many genes consecutively positioned along a chromosome.
Thus recessive alleles within this hemizygous region will be expressed.
The recessive is said to be pseudo-dominant when the homologue is paired with the
deletion.
Deletions permit mapping the location of genes on a cytogenetic map
Deletion loop-absence of a chromosome segment when homologous chromosomes pair
(at meiosis)
Figure 17-3 (7th) in the text.
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:
Deletions can be 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 - unlike many other mutations - cannot revert absence of
DNA
Duplications
Duplications come in two major forms:
Tandem - abcdecdef-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
See Fig. 15-19 (8th) 17-1b (7th)
ab cde cde f-o-ghij 2 copies
X
ab cde cde f-o-ghij 2 copies
Result:
abcdecdecdef-o-ghij 3 copies
abcdef-o-ghij 1 copy
Duplications can be recognized by:
1) Cytologically - duplication loop Fig 17-9 (7th)
2) Usually not recessive lethal - duplication genes
3) Can revert and at relatively high rate (crossing over)
Inversions
Chromosome rearrangement with segment inverted. Inversions have
two major types, which depend upon the positions of the breakpoints in
relation to the centromere
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Lecture 21; 2007
Biology 207; Section B2; Good
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
Pairing at meiosis See Fig 15-22, 15-23 (8th) 17-16, 17-17 (7th).
Paracentric inversions – Fig 15-22 (8th) 17-16 (7th)
When an inversion homolog pairs with a normal sequence homologue an inversion loop
results.
The effect of a single cross over event within the loop is the production of an acentric
fragment, which is lost and deletion products.
These deletion products, if incorporate 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.
Consequence is that:
1) "recombinants" (vs. parentals) will be reduced in frequency recombinant chromosomes are inviable.
2) 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 double cross over nvolving
the same chromatids of the first cross over event.
3) Also inversions inhibit the actual pairing of regions near, or inbetween
the break points, then crossing-over can not take place.
Pericentric Inversions - Fig 15-23 (8th) 17-17 (7th)
The effects are much the same. The actual products are different (no acentric
fragments).
Note: 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.
Translocations – Fig 15-24 (8th) 17-23 (7th)
Reciprocal translocation - heterozygous with normal chromosomes.
There are consequences for the pairing at meiosis.
Two normal homologues (N1, N2) (Brown, Purple)
Two translocation chromosomes (T1, T2)
Homologous regions of each chromosome synapse
Result is a pairing configuration that involves two pairs of
homologues. 4 chromosomes in total (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.
Adjacent - 1 segregation
T1 with N2 (Top two)
N1 with T2 (Bottom two)
The result is unbalanced gametes: duplication/deficient
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Lecture 21; 2007
Biology 207; Section B2; Good
Unbalanced gametes are inviable.
It is called adjacent because adjacent centromeres move to the same poles.
Alternate segregaton
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.
Adjacent-1 and alternate happen equally frequently
Only 50% of the products are viable.
This reduction in viable gametes reduces the fertility of heterozygote
translocation bearing individuals.
Only semi-sterile.
Translocations and Inversions result in reduced fertility due to inviable gametes.
Inviable gametes are meiotic products that are capable of forming sex cells but when
joining the normal complementary gametes are unable to form a viable zygote (it is due
to the unbalanced gamete).
Inversions and Translocations can also affect the linkage between marker loci on the
chromosomes involved.
Figure 15:19 (Ed. 8 p. 496)
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