Change in Chromosome Structure
Sometimes, there can be breakage of a chromosome. It can produce variety of arrangements. These arrangements affect the genes of that chromosome. There are following types of chromosomal structural changes:
1. Insertion or Addition: A portion of one chromosome has been deleted from its normal place and inserted into another chromosome.
2. Deletion or Deficiency: Loss of a part of chromosome is called deletion.
3. Duplication: Addition of genes in a part of chromosome is called duplication.
4. Inversion: Rearrangement of genes in a part of chromosome is called inversion.
5. Translocation: Exchange of segments between non-homologous chromosomes or transfer of a segment of chromosome to another chromosome is called translocation.
Insertion:
A portion of one chromosome has been deleted from its normal place and inserted into another chromosome (Fig. 8).
Fig. 8: Insertion
Deletion:
The loss of part of chromosome is called deletion. Fragments without centromeres are usually lost during cell division. Therefore, the chromosome will miss certain genes. This causes several serious genetic diseases. Deletion may occur due to:
Ø Losses from translocation,
Ø Crossovers within an inversion
Ø Unequal crossing over
Ø Breaking without rejoining
Fig. 9: Deletion
Types of Deletions:
There are two types of deletions (Fig. 11):
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| Fig. 10: Alterations of chromosome structure |
2.a. Interstitial Deletion:
In this case, internal part of a chromosome is missing.
2.b. Terminal Deletion:
In this case, there is only one break and the homologous chromosome fail to rejoin. Thus tip of the chromosome is lost in cell division.
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| Fig. 11: Types of deletions: (A) Terminal deletion, (B) Interstitial deletion |
Effects of Deletion:
Small deletions are not fatal. But large deletions are usually fatal. Some medium-size deletions lead to human disorders. Known disorders in humans include Wolf-Hirschhorn syndrome, which is caused by partial deletion of the short arm of chromosome 4; and Jacobsen syndrome, also called the terminal 11q deletion disorder.
2.1. Homozygous deletions are lethal. They cause abnormal developments.
2.2. In some deletions, number of base pairs is not equally divisible by three. It causes a frameshift mutation. Thus all of the codons coming after the deletion are read incorrectly during translation. It produces a severely altered and non-functional protein.
2.3. Deletions cause male infertility and two thirds of cases of Duchenne muscular dystrophy. A deletion of part of the short arm of chromosome 5 results in Cri du chat. It is also known as cry of the cat syndrome. It is named from French words for cry of the cat. Individuals heterozygous for the deletion and a normal chromosome have karyotype 46 del(5)(p14). The term in parentheses indicate that bands in region 14 of short arm (p) of chromosome 5 is missing. These individuals may be severely impaired. The surviving infants have a distinctive cry (catlike), severe mental and physical retardation, and shortened life span. It is found in 1 in 50,000 live births.
2.4. Heterozygous deletion may cause pseudo-dominance. In this case, dominant allele is missing. Therefore, recessive allele expresses itself.
Duplication:
Addition of genes in a part of chromosome is called duplication. In this case, the fragment joins to the homologous chromosome with a duplication of genes. It adds one or more gene in the chromosome. Therefore, the organism carries same gene repeated in its haploid chromosome. Gene duplication occurs due to following reasons:
Ø Error in homologous recombination
Ø Duplication of an entire chromosome leads to the duplication of a region of DNA containing a gene.
Fig. 12: Duplication
Types of Duplications:
There are following types of duplications (Fig. 13):
3.a. Tandem Duplication:
In this case, the duplication is adjacent to the normal chromosome. It has same order as the original order. It is believed that the homologous chromosomes overlap each other. Therefore, the segments break simultaneously at different points. If different homologous chromosomes reunite, one chromosome has tandem duplication and other has deletion of duplicated region. Thus the duplication and deletion are reciprocal to each other.
3.b. Reverse Duplication:
In this case, duplication is also adjacent to normal chromosome. But the order is reverse as compared to original order.
3.c. Displaced Duplication:
In this case, the duplication is not adjacent to the normal segment.
3.d. Heterokaryotypic Duplication:
Fig. 13: Types of duplications
Effects and Significance of Duplication:
3.1. The homozygous or heterozygous individuals for small duplicated segments are viable. Further evolutionary changes can occur in this individual.
3.2. Duplication has great significance for evolutionary biology. The effected individuals have two genes. It has a single functional gene. This gene has a slow mutation rate. This individual also has one copy of a duplicate set of genes. This gene is free from selective pressure. It can freely mutate as two copies of genes are present. Therefore, mutations in just one copy of gene has no deleterious effect on the organism. Thus the second copy is free to mutate randomly.
3.3. Major genome duplication events also occur. It is predicted that the entire yeast genome underwent duplication about 100 million years ago. Plants are the most important genome duplicators. For example, wheat is hexaploid. It has six duplicate copies of its genome.
3.4. Known human disorders include Charcot-Marie-Tooth disease type 1A, which may be caused by duplication of the gene encoding peripheral myelin protein 22 (PMP22) on chromosome 17.
Inversion:
Rearrangement of
genes in a part of chromosome is called inversion. A portion of the chromosome
has broken off, turned upside down, and reattached, therefore the genetic
material is inverted. In this case, the fragment reattaches to the original
chromosome but in reverse orientation. An inversion occurs when a single
chromosome undergoes breakage and rearrangement within itself.
Types of Inversions:
Inversions are of two types (Fig. 14):
4.a. Paracentric Inversions:
These inversions do not include the centromere. Both breaks occur in one arm of the chromosome.
4.b. Pericentric Inversions:
It includes the centromere and there is a break point in each arm.
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| Fig. 14: Types of inversions |
Effects of Inversion:
4.1. In some cases, the rearrangement is balanced after inversion. Thus there is no extra or missing genetic information. Such inversions usually do not cause any abnormalities in carriers. However, there is an increased chance for production of unbalanced chromosome rearrangements in offspring of carriers. Families that may be carriers of inversions must undergo genetic counseling and genetic testing.
4.2. The most common inversion seen in humans is on chromosome 9. This inversion is generally having no deleterious or harmful effects. But it may lead to an increased risk for miscarriage for about 30% of affected couples.
Translocation:
The interchange of parts between non-homologous chromosomes is called chromosome translocation. A portion of one chromosome has been transferred to another chromosome. It is detected in cytogenetics or in a karyotype of affected cells.
Types of Translocations:
There are two main types of translocations: (Fig. 15)
5.a. Reciprocal (Non-Robertsonian) Translocations:
It is caused due to an exchange of material between non-homologous chromosomes. Reciprocal translocations are found in about 1 in 600 newborns. Such translocations are harmless. However, carriers of balanced reciprocal translocations can form gametes with unbalanced chromosome translocations. It may cause miscarriages or children born with abnormalities. Genetic counseling and genetic testing is required for such families.
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| Fig. 15: Types of translocations |
5.b. Robertsonian Translocations:
This type of rearrangement involves two acrocentric chromosomes. These chromosomes fuse near the centromere region with loss of the short arms. As the two chromosomes have fused together so the resulting karyotype has only 45 chromosomes. Robertsonian translocations have all combinations of acrocentric chromosomes. The most common translocation involves chromosomes 13 and 14. It is seen in about 1 in 1300 persons. The carriers of Robertsonian translocations are phenotypically normal. But there is a risk of unbalanced gametes. It may lead to miscarriages or abnormal offspring. For example, carriers of Robertsonian translocations in chromosome 21 have a higher chance to have a child with Down syndrome.
Effects of Translocations:
5.1. Cancer: Several forms of cancers like leukemia are caused by translocations.
5.2. Infertility: Sometimes, one parent carries a balanced translocation. The parent is normal. But conceived fetuses are not viable.
5.3. Down's Syndrome: 5% or less cases of Down's syndromes are caused by a Robertsonian translocation.
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