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WEB TUTORIAL 8.3
Aberrations
OVERVIEW
The rearrangement of chromosome segments is mainly caused by one or more breaks
along the axis of the chromosome, followed by gain or loss of genetic material. This tutorial describes the types of structural changes that occur in chromosomes and the effects
they can have on individuals.
TEXTBOOK REFERENCES
Variation Occurs in the Structure and Arrangement of Chromosomes (pp. 198-199)
Types of Chromosome Aberrations
The major types of chromosome aberrations are
Deletions
Duplications
Inversions
Nonreciprocal translocations
Reciprocal translocations
Deletions
When a chromosome breaks in one or more places and a piece is lost, the chromosome
with the missing piece is referred to as a deletion chromosome. A deletion may be at the
end of a chromosome (a terminal deletion), or it may be in the interior of the chromosome
(an intercalary deletion).
The portion of the chromosome with the centromere will usually be maintained as the cell
divides, and the other segment will eventually be lost following meiosis or mitosis.
Intercalary deletions can be detected in cells undergoing meiosis when pairing of
homologs shows a loop structure, called a deficiency loop, where a piece is missing.
Terminal Deletion Example
In humans, a region near the end of chromosome 5 breaks easily. When the terminal piece
is lost (it has no centromere and is lost during cell division), the result can be a gamete carrying a deletion.
Fertilization of the gamete forms a zygote that is heterozygous for the deletion.
This genotype results in a child with Cri-du-chat syndrome, characterized by retardation
and a weak, high-pitched, catlike cry.
Intercalary Deletions and Deficiency Loops
In Drosophila, salivary gland cells contain large chromosomes called polytene chromosomes. The chromosomes have duplicated many times, but they do not segregate from
each other and the cells do not divide. Moreover, the homologous pairs remain tightly
synapsed. The resulting polytene chromosomes have easily visualized banding patterns
specific to each chromosomal region.
Evidence of an intercalary deletion can be seen when a synapsed homolog forms a deficiency loop. Here the fly is heterozygous for a deletion spanning several well-studied
bands.
Duplications
Duplications occur as a result of uneven crossing over during prophase of meiosis. Note
that the tetrad is mispaired during synapsis. A single crossover between chromatids 2 and
3 results in deficient and duplicated chromosomal regions. The two chromosomes not
involved in the crossover event remain normal in their gene sequence and content.
Following segregation, cells contain a chromosome with a duplication, a chromosome
with a deletion, or a normal chromosome.
Duplications are a repeated part of the genetic material.
Duplications can be detected during meiotic pairing when the extra chromosomal material loops out (similar to the type of pairing seen in a deletion).
Examples of Duplications
When region 16A of the X chromosome of Drosophila is duplicated, a phenotype called Bareye results. Bar-eye is more pronounced if the duplications are all on one of the two X chromosomes in females instead of being distributed evenly on both chromosomes. This difference in severity is an example of a position effect.
Unequal crossing over accounts for the formation of the most extreme genotype, BB.
Several serious human diseases are caused by repeated three-base sequences. The severity of the disease increases with increased copy number of the repeat.
Huntington disease, a dominant neurological disorder with onset in middle age, is such a
disease. Normal individuals have 6-35 CAG repeats. Individuals with the disease have
many more.
Duplications in Evolution
Duplications play an important role in evolution. This idea was proposed by Susumo
Ohno in his monograph Evolution by Gene Duplication, published in 1970. Ohno proposed
that single-copy genes are not free to mutate because they are essential to the cell.
Duplications, however, are not needed, and over time, these duplicated sequences could
acquire a new function for the cell.
The discovery of many gene families with related sequences suggests that Ohno was correct.
The gene families include
Hemoglobin and myoglobin
Digestive enzymes trypsin and chymotrypsin
T-cell receptors and antibodies
Inversions
Inversions change the linear gene sequence on a chromosome. Inversions are the result of
breakage and rejoining of chromosome material.
When inversions involve the centromere (pericentric inversions), they can sometimes be
detected by a change in the ratio of arm lengths.
In contrast, inversions that do not include the centromere (paracentric inversions) leave
arm ratios unchanged.
When genes change their position in a chromosome, their phenotype may be altered (position effect). This can happen when genes are placed near an inactive condensed area of the
chromosome and are repressed.
For example, as shown at left, when the allele for normal red eye in this fruit fly is present, the eye is red. When the normal gene is moved to near the centromere (a heterochromatic area), allele expression is partially repressed and the eye is mottled red and white.
Evolutionary Advantages of Inversions
Inversions may also protect a set of linked genes from recombination. If these genes are
evolutionarily coadapted, a lack of recovered recombination in this region may offer the
organism a selective advantage. Keep in mind that recombination does occur in the region,
but the gametes usually die and are not recovered in the progeny.
Paracentric Inversion Pairing
When pairing occurs during meiosis between a chromosome with an inversion and a normal chromosome (each with two chromatids), one chromosome must form a loop to pair
gene-to-gene with the other.
If no crossing over occurs, the gametes will have parental (nonrecombinant) chromosomes, with half having a normal sequence of genes and half having an inverted sequence.
If crossing over occurs within the looped region, serious chromosome aberrations can
result. The kind of aberration depends on whether the inversion involves the centromere
(pericentric) or not (paracentric). One chromosome must form a loop to pair gene-to-gene
with the other.
Two of the derived chromosomes are normal and will segregate correctly in meiosis.
One chromosome is dicentric (two centromeres) and has both duplicated and deleted
material. If the two centromeres go to different poles during cell division, the chromosome
will tear, creating unstable ends and loss of material. This can create an inviable gamete.
Translocations
Translocations can be detected by pairing behavior during meiosis in which translocation
heterozygotes often form a crosslike structure.
Homologous portions of the chromosomes pair with each other in meiosis.
Translocation Segregation Patterns
Possible segregation patterns are shown here.
Some gametes will be normal. Some will have all of the genetic material normally present
in a gamete but in a translocated configuration. This is called a balanced translocation.
Translocations also lead to the production of gametes with duplicated or deleted material.
Such gametes tend to be inviable and to result in death if they participate in fertilization.
Robertsonian Translocations
A common type of translocation seen in humans is a Robertsonian translocation, in which
the long arms of two chromosomes fuse together at the centromere and small, acentric,
heterochromatic ends are lost.
One type of Robertsonian translocation results in an inherited form of Down syndrome.
Down syndrome usually results from the presence of three copies of chromosome 21.
In some cases, a parent may be a carrier of a balanced translocation for chromosome 21.
Gametes produced by a balanced translocation carrier are shown in part (a) of the figure.
When fertilized by a normal gamete (part b), the offspring shown in part (c) can result.
Note that some children will have Down syndrome and some will be balanced translocation carriers who are phenotypically normal but will have Down syndrome children.
CONCLUSION
Chromosome aberrations are structural changes in chromosomes that include duplications, deletions, inversions, and translocations. Large segments of the chromosome can be
modified by deletions or duplications. Deletions occur when a piece of chromosome is
lost, and they can produce serious conditions such as the Cri-du-chat syndrome in
humans. Duplications occur as a result of unequal crossing over during meiotic prophase
and have been particularly important as a source of redundant or new genes. Several gene
families, whose loci have similar structure and function, have confirmed the evolutionary
importance of duplications. Inversions and translocations change the gene order along
chromosomes and may initially cause little or no loss of genetic information or deleterious
effects, aside from alterations of phenotype due to position effects. However, these
rearrangements may lead to the production of genetically abnormal gametes during meiosis, resulting in lethality. A "Robertsonian” translocation results in the fusion of the long
arms of two chromosomes and loss of the short arms.
YOU
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SHOULD NOW BE ABLE TO
List the major categories of chromosomal rearrangement and describe how they
can be detected during meiosis.
Explain the mechanism by which duplications can occur.
Explain the evolutionary advantages of duplications and inversions.
Give examples of diseases resulting from chromosomal rearrangements.
Explain the difference between a paracentric and a pericentric inversion.
Describe how chromosomal rearrangements can lead to the production of genetically abnormal gametes during meiosis.
KEY TERMS
deficiency loop
duplication
intercalary deletion
nonreciprocal translocation
paracentric inversion
pericentric inversion