Chromosomal Aberrations or Variations in the structure of Chromosomes

 

Chromosomes are the structures which carry genes in a definite linear order. Chromosomes have a definite structure and organization, which is normally constant from one cell division to the next. They, however, sometimes undergo certain structural modifications which are known which are known as chromosomal aberrations. Since, these modification also result in a change in the organism, they are also called chromosomal mutations.

Breakage Fusion-Bridge Cycles:

Breaks in the chromosome are necessary for any structural changes. After break the chromosome may remain un united. When this happens, the part of the chromosome without the centromere is lost, since, spindle fibres attach only to the centromere.

Sometimes, the broken ends may join immediately and the original chromosome is restored (restitution). At other times, the broken ends may join the segments produced by other breaks (non-restitutional union), resulting in structural changes.

McClinctok studied the broken ends of chromosomes in the maize. A chromosome break occurs, and is followed by duplication of the chromosome during prophase. As a result, two chromatids are formed. The broken ends of the chromatids behave as if they are ‘sticky’, and undergo fusion. This results in the formation of a chromatid with two centromere (dicentric chromatid). During anaphase, spindle fibres are attached to the two centromeres. As a result, the chromatid stretches out, forming a bridge from one pole to the other. This bridge may break, but at different point, producing a deficiency and a duplication.

Chromosomal abberations are of four types : 1. Deletions or Deficiencies, 2. Duplications, 3. Inversions, and 4. Translocations.

Deficiencies:

Loss of chromosomal segment resulting in the loss of genes is called as Deficiency or Deletion. The deleted portion will not survive in the higher organisms if it lacks a centromere, because it will have no capacity for movement in Anaphase. The portion of the chromosome carrying the centromere functions as a genetically deficient chromosome.

Deficiencies can be terminal or interstitial.

If the single break occurs near the end of the chromosome, it is called terminal deletion. Generally, if a terminal break occurs the broken piece attaches to the terminal portion of the same chromosome. When restitution takes place no change is observed in the chromosome.

But sometimes, the broken fragment do not join. If the broken fragment do not contain a centromere, then it will not go to the either of the poles as spindle fibres cannot attach to it. Then this fragment ultimately disappear in the cytoplasm.

Sometimes, two breaks occur at any two points, releasing an intercalary segment. The broken ends of the original chromosomes may again fuse, resulting in an intercalary or interstitial deficiency.

Both terminal and intercalary deficiencies can be observed during pachytene stage of meiosis or in the polytene Chromosomes. Pairing of chromosomes takes place chromomere to chromomere. If a segment is missing from the chromosome, then the homologous chromosome containing this segment will form a loop during pairing. This is called deletion loop.

A deletion represent a quantitative change in the genotype in that it involves the loss of of genetic material, so it would be expected that deficiencies would have deleterious effect on an organism, the effect depending upon the amount of genetic material and it's specific function.

Deletions, unlike, other mutations generally donot revert, or mutate back, to the wild type chromosome.

In deletion heterozygotes, recessive alleles on the normal Chromosomes are expressed because the deletion chromosome is missing the homologous regions. Expression of recessive alleles in such cases, is called pseudo dominance.

A well known example in the humans is the deletion of one half of the short arm of chromosome 5 (5p) which, when heterozygous, causes the Cri- du- chat ( cry - of the - cat) syndrome. Infants with this syndrome  generally have characteristic high-pitched, cat like cry as well as microcephally (small head) and several mental retardation.

 Duplications:
when a chromosomal segment is represented twice, it is called as duplications. duplications originates out of unequal crossing over. There are 4 types of duplications

1. Tanden Duplication:

the duplication is present adjacent to the original chromosomal region in the same order as the original sequence, then this type of duplications are called tandem duplications.. for example, if duplication repeat is ABC, a tandem dulication will be ABC ABC, DEF.

2.Reverse Tandem Duplication:

the duplication is present adjacent to the original chromosomal region but in the reverse order of the original sequence, then this type of duplications are called Reverse Tanden Duplications. For example, if the duplication repeat is ABC, a reverse tandem duplication will be ABC CBA DEF.

3. Displaced Duplication:

The duplicated chromosomal segment is located on the same chromosome but away from the original segment i.e., the duplicated region is not present adjacent to the original segment., resulting in a displaced duplication.

4. Transposed Duplication:

The duplicated chromosomal segment is located on a non-homologous chromosome.

when an individual is heterozygous for a duplication and normal chromosome, the duplicated region doesnot have a homologous segment to pair with in Meiosis. As a result a loop of the duplicated region may develop.

one of the classical examples of duplication in Drosopohila is Bar eye character. the wild type eye is large and has an average 779 facets or ocelli. it has two bar region, one on each X chromosome. by the study of gaint salivary gland chromosomes, it could be demonstrated that 'Bar' character was due to a duplication in region 16A of X-chromosome. the normal males have 16A region represented once, Bar-males has two Bar regions with elongated eyes with 358 facets and Bar-Double males has three Bar regions with 45 facets.

in females, the wild B^+/B⁺ has nearly 800 facets in each of its eyes; in the heterozygote B/ B⁺  , the number is reduced to about 360; while the homozygous B/B, the eye is reduced to about 70 facets, arranged in long, narrow eye structure..

As might be expected, duplications are observed more frequently in nature and are less likely to be lethal to the individual than are deficiencies.

Inversions:

Most of the homologous chromosomes in a population have genes in the same sequence. However, sometimes the sequence of genes in a chromosome is altered by the rotation of a chromosome segment through 180⁰. Alterations in the sequence of genes is called inversions.

So, in inversions a chromosome segment contains genes in a sequence which is reverse of normal. For example if a chromosome having gene alignment a b c d e f g h i, breaks at two points b and g and the middle segment c d e f g undergoes inversion, then an inverted chromosome segment if formed with the sequence a b g f e d c h i.

Due to inversions there is no increase or decrease in number of genes. Only re-arrangement of genes occur.  Inversions are of two types:

Paracentric Inversion:

When both the breaks in the chromosome occur on the same side of the centromere, i.e., the inverted segment does not contain centromere, then such type of inversions are called paracentric inversions.

Pericentric Inversion: (peri=around).

The inverted segment contains the centromere i.e., it involves the one break on either side of the centromere.

Inversions arise by the formation of loops on a chromosome. Breaks may occur at the point of intersection of the loops. Reunion of the broken ends takes place in a new combination, and an inversion results. The paracentric inversion results in an acrocentric chromosome just like the non-inverted chromosome, but that the pericentric inversion results in a metacentric chromosome, because the position of the centromere has been changed.

Individual heterozygous for an inversion can be recognized by the presence of inversion loop in meiotic pachytene chromosomes. These structures occur because of the affinity of the two homologous, and the only way two homologous can pair is if one twists on itself and makes a loop while the other makes a loop without twist.

In paracentric inversion, a single cross over or an odd number of cross overs in inverted region results in the formation of a dicentric chromosome (having two chromosomeres) and an acentric fragment (with no centromere). The dicentric chromosome and acentric fragments are observed at anaphase-I, in the form of anaphase bridge and fragment. Crossing over within and outside inversion lead to various kinds of deficiencies and duplications.

Inversions reduce the frequency of recombination between any two genes. Thus, they are called cross over suppressors.

Translocations:

 When a segment of one chromosome is detaches and joins to a non-homologous chromosome, it is called translocation. It is different from crossing over, which involves an interchange between segments of homologous chromosomes.

There is no addition or loss of genes during translocation, only a re-arrangement i.e., change in the sequence and position of a gene, occurs.

Translocations are of the following types:

Simple translocations:

A single break occur in a chromosome. The broken segment gets attached to one end of a non-homologous chromosome. This type of translocations are very rare.

Shift translocation:

A chromosome breaks at two places. A simple break occurs in the other non-homologous chromosome. The broken part gets inserted interstitially in a non homologous chromosome.

Reciprocal translocation:

A segment from one chromosome is exchanged with a segment from another non-homologous chromosome, such type of translocation are called as reciprocal translocations. As a result, two translocation chromosomes are simultaneously achieved.

Reciprocal translocations are of two types:

a.      Homozygotic translocation:

Tranlocation involves both the members of each of the homologous chromosomes. This type of translocation occurs rarely, and exhibit normal meiotic behaviour. Hence, they are difficult to detect cytologically unless morphologically dissimilar chromosomes are involved.

b.     Heterozygotic translocation:

Translocation involves only one member of each of the homologous pair.

Normal pairing into bivalents will not be possible among chromosomes involved in heterozygotic translocation. Due to pairing between homologous segments of chromosomes, a cross shaped (+) figure involving four chromosomes will be observed during pahcytene.