STRUCTURAL ALTERATIONS IN CHROMOSOMES

The expression and inheritance of the sum total of characters of an organism is determined by the number and sequence of genes of its cells.
The changes in architecture and morphology of chromosomes do not involve changes in the number of chromosomes, but result from changes in the number or sequence of genes of chromosomes.
These changes are collectively known as chromosomal aberrations and were first analyzed by Muller (1928) in Drosophila and by Barbara McClintock (1930) in Zea-mays.
Cytological observations along with genetic studies have resulted in the identification of following types of changes in the number or arrangement of genes:

All types of chromosomal aberrations are caused by a break in the chromosome or its chromatid.
When broken ends rejoin to restore the original chromosome structure and gene sequence, there is no change and restitution occurs.
Aberrations occur when broken ends are lost or get joined to a wrong chromosome or in a wrong order.
The number of breaks, their location, and the pattern in which broken ends get joined determines the type of chromosomal aberration.
Their study is important because they occur in nature quite frequently and have been instrumental in the evolution of many species of plants and animals.
Their frequency can be increased with the help of ionizing radiations or certain chemical agents.

A. Changes Involving Number of Genes

i) Deletion or deficiency

It signifies the loss or absence of a section of a chromosome and may involve one or more genes.

ii) Duplication.

It represents a gain in chromosomal material and in this case a part of a chromosome is present in excess of the normal amount. Thus one or more genes are present in more than two doses.

B Changes Involving Arrangement of Genes

i) Inversion.

In this process a section of a chromosome gets inverted or rotates by 180° on its own axis. This changes the relative positions of genes on a chromosome, but not their number.

ii) Translocation.

It involves the transfer of a part of one chromosome to a nonhomologous one, thereby changing the relative positions of genes but not their number.

Deletion or Deficiency

If a section of chromosome gets broken and detached, some genes are lost from the chromosome.
Acentric fragments are either digested by nucleases or fail to move to either of the poles during cell division.
Usually they get excluded from the daughter cells.
Sometimes they move towards one end of the cell, just by chance, and get included in one of the two daughter cells.
In either case a population of cells arises which is deficient for a few genes.
If gametes arise from deficient cells, deletion is transmitted to the next generation.
These are the following type

Terminal Deletion

In this type of Deletion a terminal section of chromosome is absent,
Only one break is necessary for terminal deletion,
Broken acentric fragments of chromosomes, which are in the process of being digested, sometimes appear as small chromatin bodies in cells and are known as micronuclei.

Intercalary Deletion

In this type of deletion an intermediate section or portion of chromosome is lost.
for intercalary deletion two breaks (one on either end of the deleted region) are essential.
A break for intercalary deletion results into three pieces of chromosome, the middle one of which is lost and the other two get joined again.

Experimental proof for deletion was obtained by Bridges (1916-1919) who studied the inheritance pattern of sex linked lethal characters which had arisen spontaneously in a population of fruit-flies.
Deletion can be recognized by distortions of chromosomes during meiosis pairing of homologous chromosomes or during somatic pairing in specialized tissues like salivary glands of Drosophila.
Due to a terminal deletion one of the paired chromosomes appears to be much longer than the other.
This can be seen during pachytene in maize and in salivary gland chromosomes of Drosophila.
Due to an intercalary deletion the normal chromosome forms a loop near the deficient region of its homologous, because only identical regions pair with each other.
Inheritance patterns of genes of deleted regions and cytological studies of pairing between normal and deleted chromosomes have helped a lot in finding out the relative positions of genes on chromosomes.
Thus, deletions have helped in constructing and verifying linkage maps of a variety of organisms like maize, Drosophila, bacteriophages etc.

Duplication

The presence of a part of a chromosome in excess of the normal complement is known as duplication.
A broken section of a chromosome attaches itself to a normal homologous or non homologous chromosome or in the presence of a centromere behaves like an independent chromosome and gets included in an otherwise normal nucleus.
Consequently some genes are present in a cell in more than two doses.
Depending on the mode of joining of the duplicated region to a chromosome or its independent existence,
duplications can be of the following types:

1) Extra-chromosomal duplication.

In the presence of a centromere the duplicated part of a chromosome may behave as an independent chromosome.

2) Tandem duplicated.

In this case the duplicated region situated just by the side of the normal corresponding section of the chromosome and the sequences of genes are the same in the normal and duplicated regions.

For example, if the sequence of genes in a chromosome is ABC.DEFGH (full stop represents the centromere) and if the section containing the genes DEF is duplicated, the sequence of genes in tandem duplication will be ABC.DEFDEFGH.

3) Reverse tandem duplication.

In this case the sequence of genes in the duplicated section of a chromosome is just the reverse of a normal sequence. In the above example, therefore, the sequence of genes as a result of reverse tandem duplication will be ABC.DEFFEDGH.

4) Displaced duplication.

In this case the duplicated section is not adjacent to the normal section Depending on whether the duplicated portion is on the same side of the centromere as the original section or on the other side; displaced duplication can be homobrachial or heterobrachial:

homobrachial duplication = ABC.DEFGDEFH.

heterobrachial duplication = ADEFBC.DEFGH.

5) Transposed duplication.

In this case the duplicated section is attached to a non homologous chromosome.
If ABC.DEFGH and LMNOPQ.RST represent the genes sequences of two non homologous chromosomes, a transposed duplication will result into chromosomes with gene sequences ABC.DEFGH and LMNDEFOPQ.RST.
The duplicated region can be transposed to a non homologous chromosome interstitially or terminally.

Duplications involving various regions of the X chromosome in Drosophila have been studied in detail.
Flies heterozygous for the Bar (B) gene have rod shaped or rectangular eyes instead of normal round eyes.
Flies homozygous for this gene have very small eyes.
In 1936 Muller and Bridges found independently of each other that bar eyes are caused due to a duplication of the region of the X chromosome.
A reduplication of this region results into Ultrabar or doublebar or very small eyes.

Duplications and reduplications of the Bar region can be very easily seen in the salivary gland chromosomes.
As the number of Bar genes increases, the eyes become smaller.
Duplications, reduplications and deletions may arise due to unequal crossovers.

Like deletions duplications also result in unequal or looped out configurations at the time of pairing of homologous chromosomes. Crossing –over in reverse tandem duplication results in a dicentric chromosome.
This can frequently be seen in chromosomes of maize.
Irrespective of whether sister or non-sister chromatids are involved in a cross-over, dicentric chromosomes are produced.
As the two centromeres move towards two different poles, a chromosome “bridge” is formed which later on breaks at any point along the bridge.
The broken ends become “sticky” and a replication of the chromosome produces two sister chromatids which are joined together due to their sticky ends.
Therefore, the bridge-breakage-fusion cycle goes on indefinitely.
In sporophytic tissues of plants however, sticky ends are not found.

Duplication has played a great role in evolution.
It is a means of increasing the number of genes in a cell so that different copies of the same gene may change in different directions without disturbing the normal functions of an organism.
It has been suggested that all cases in which different gene pairs affect the same character (e.g. multiple factors, complementary genes, etc.) arose initially as duplications of single genes .
More evolved organisms have been found to have more repetitions of DNA sequences.

🔬 Structural Chromosomal Alterations – MCQs

🔁 Section A: Duplication

Which of the following best describes chromosomal duplication?
A. Loss of a chromosome segment
B. Repetition of a chromosome segment
C. Exchange of segments between chromosomes
D. Inversion of a segment
Answer: B
Tandem duplication is a type of:
A. Terminal deletion
B. Inversion
C. Adjacent duplication
D. Gene amplification
Answer: C
Which scientist discovered the Bar eye mutation in Drosophila caused by duplication? (PYQ – BSc 2021)
A. Watson
B. Crick
C. Muller
D. McClintock
Answer: C
Bar eye mutation in Drosophila is an example of:
A. Terminal deletion
B. Inversion
C. Duplication
D. Reciprocal translocation
Answer: C
Unequal crossing over leads to:
A. Deletion
B. Translocation
C. Duplication
D. Point mutation
Answer: C
The pairing of duplicated chromosomes during meiosis often results in:
A. Loop formation
B. Bridges
C. Gaps
D. Dicentric chromosomes
Answer: A
The evolutionary significance of duplications is mainly due to:
A. Lethality
B. Formation of multivalents
C. Creation of new genes
D. Chromosome loss
Answer: C
A reverse tandem duplication differs from tandem duplication in:
A. Gene content
B. Gene orientation
C. Location of duplication
D. Loop formation
Answer: B
Which term describes duplications where the duplicated segment is inserted elsewhere?
A. Tandem duplication
B. Terminal duplication
C. Transposed duplication
D. Intercalary duplication
Answer: C
The effect of gene duplication on phenotype is often due to:
A. Dominance
B. Gene silencing
C. Dosage effect
D. Transposition
Answer: C

❌ Section B: Deletion (Deficiency)

A chromosomal deletion is best defined as:
A. Removal of a chromosome
B. Loss of a segment of chromosome
C. Rearrangement of genes
D. Addition of genes
Answer: B
Terminal deletion occurs at the:
A. Middle
B. Both ends
C. End of a chromosome
D. Centromere
Answer: C
Intercalary deletion occurs when:
A. End part is removed
B. Internal segment is lost
C. Whole arm is deleted
D. No deletion happens
Answer: B
Which cytological structure indicates deletion during meiosis?
A. Multivalent
B. Loop
C. Inversion loop
D. Deletion loop
Answer: D
Deficiency heterozygotes often show:
A. No pairing
B. Bridges
C. Loops
D. Univalents
Answer: C
Deletion mapping is a technique used to:
A. Detect centromeres
B. Locate genes
C. Repair deletions
D. Clone DNA
Answer: B
In maize, the bridge-breakage-fusion cycle is associated with: (PYQ – BSc 2022)
A. Duplication
B. Inversion
C. Deletion
D. Translocation
Answer: C
Who discovered the bridge-breakage-fusion cycle in maize?
A. T.H. Morgan
B. Barbara McClintock
C. Watson
D. Beadle
Answer: B
Chromosome deletions are often:
A. Lethal in homozygous condition
B. Dominant
C. Useful
D. Found in all plants
Answer: A
Which of the following is NOT a consequence of deletion?
A. Pseudodominance
B. Deletion loop
C. Gene silencing
D. Lethality
Answer: C

🔃 Section C: Inversion

A paracentric inversion includes:
A. Centromere
B. Only telomere
C. A region not including centromere
D. Entire chromosome
Answer: C
A pericentric inversion includes:
A. Only one arm
B. Centromere
C. Telomere only
D. Non-coding region
Answer: B
Inversion heterozygotes form which structure during meiosis?
A. Trivalent
B. Circle
C. Inversion loop
D. Tetrad
Answer: C
Paracentric inversion crossover results in:
A. Two normal chromatids
B. One acentric and one dicentric chromatid
C. Four viable chromatids
D. Insertion
Answer: B
Pericentric inversion crossover can lead to:
A. No effect
B. Duplications and deletions
C. Balanced gametes
D. Multivalents
Answer: B
Inversions suppress crossing over in:
A. Homozygotes
B. Heterozygotes
C. Diploids
D. Triploids
Answer: B
Inversion loops are visible under:
A. Phase contrast microscope
B. Electron microscope
C. Light microscope
D. Fluorescent microscope
Answer: C
Inversions are significant in evolution because they:
A. Delete genes
B. Increase mutation rate
C. Preserve gene blocks
D. Break genes
Answer: C
Which of the following is most likely sterile due to crossover suppression?
A. Duplication homozygote
B. Deletion homozygote
C. Inversion heterozygote
D. Translocation homozygote
Answer: C
A single crossover in a paracentric inversion leads to:
A. Viable gametes
B. Balanced chromosomes
C. One acentric and one dicentric chromatid
D. Equal crossing over
Answer: C

🔄 Section D: Translocation

A translocation involves:
A. Movement within same chromosome
B. Exchange between non-homologous chromosomes
C. Duplication of chromosome
D. Loss of centromere
Answer: B
Reciprocal translocation involves:
A. Unequal exchange
B. One-way transfer
C. Balanced mutual exchange
D. Mutation
Answer: C
A translocation heterozygote during meiosis forms:
A. Circle
B. Trivalent
C. Cross or ring
D. Loop
Answer: C
Alternate segregation in translocation leads to:
A. Non-viable gametes
B. Balanced gametes
C. Lethal mutations
D. Duplications
Answer: B
Adjacent segregation in translocation results in:
A. Normal gametes
B. Balanced gametes
C. Unbalanced gametes
D. Homologous pairing
Answer: C
A quadrivalent is formed in which heterozygote?
A. Inversion
B. Duplication
C. Translocation
D. Deletion
Answer: C
Semi-sterility is often observed in:
A. Duplication homozygotes
B. Translocation heterozygotes
C. Inversion homozygotes
D. Deletion heterozygotes
Answer: B
Translocation can cause which genetic disease in humans?
A. Sickle cell
B. Cystic fibrosis
C. Down syndrome
D. Hemophilia
Answer: C (due to Robertsonian translocation)
A Robertsonian translocation occurs between:
A. Autosomes and sex chromosomes
B. Non-homologous acrocentric chromosomes
C. Telomeres
D. Centrosomes
Answer: B
Translocations are useful in:
A. Mutation breeding
B. Gene therapy
C. Speciation
D. All of the above
Answer: D

🧬 Section E: General & Conceptual

Chromosomal aberrations are first studied under microscope using:
A. Fluorescent dyes
B. C-banding
C. Staining techniques
D. kDNA analysis
Answer: C
Structural chromosomal changes often arise due to:
A. Translation errors
B. Replication errors
C. Chromosome breakage
D. Gene silencing
Answer: C
The term “structural heterozygote” refers to an organism:
A. With numerical chromosome change
B. Having mutations in one gene only
C. Heterozygous for a chromosomal rearrangement
D. Identical chromosomes
Answer: C
Meiotic behavior of a translocation heterozygote is best observed during:
A. Interphase
B. Prophase I
C. Anaphase II
D. Telophase I
Answer: B
Chromosomal rearrangements affect fertility mainly due to:
A. Increased mutation rate
B. Crossing over suppression
C. Production of unbalanced gametes
D. Protein synthesis problems
Answer: C
Cytologically visible rearrangements include all EXCEPT:
A. Duplication
B. Gene mutation
C. Inversion
D. Translocation
Answer: B
In Drosophila, the classic example of inversion is:
A. Bar eye
B. Notch wing
C. White eye
D. Curly wing
Answer: A
Homologous pairing in inversion heterozygotes requires:
A. Loop formation
B. Crossover suppression
C. Breakage
D. DNA replication
Answer: A
In duplication heterozygotes, phenotypic variation may occur due to:
A. Translocation
B. Deletion
C. Dosage effect
D. Pseudodominance
Answer: C
Which rearrangement is most likely to lead to speciation?
A. Translocation
B. Inversion
C. Duplication
D. Deletion
Answer: A