chromosome deletion terminal deletion and interstitial deletion

By Live Dr - Sun Jan 11, 1:22 pm

The Breakage and the Rejoin after breakage are the basis of chromosomal structural aberration. There are two types of structural aberration: balanced structural aberration with normal complement of chromosomal material and unbalanced structural aberration with loss or gain of chromosomal material.

Unbalanced structural aberration


A chromosome deletion occurs when the chromosome breaks and a piece is lost.

Two types: terminal deletion and interstitial deletion

Terminal deletion: one break on one arm, a terminal piece is lost.

Interstitial deletion: two breaks on one arm, a interstitial piece is lost.

This of course involves loss of genetic information and results in what could be considered “partial monosomy” for that chromosome.


Chromosome duplication is just that, a duplication of a section of a chromosome. A duplication is sometimes referred to as a ‘partial trisomy’. Trisomy refers to three. Therefore if a duplication exists, that individual has three copies of that area instead of two. This means there are extra instructions (genes) present that can cause an increased risk for birth defects or developmental problems.

Ring chromosome

Formed when a chromosome undergoes two breaks and broken ends of the chromosome reunite in a ring structure. This involves loss of genetic information just like the deletion.


One arm is deleted and the other duplicated, so one arm is monosomy and the other is trisomy. The most common isochromosome is i(Xq).

Dicentric chromosomes

As their name implies, dicentric chromosomes have two centromeres. Two chromosomes break at the same time ,then two segments with centromere rejoin, and two without centromere are deleted.

Balanced structural aberration

Balanced structural aberration is with normal complement of chromosomal material. Individuals usually have no phenotypic effects. Repeated abortion, intrauterus fetal death, stillbirth and birth defects due to the abnormal segregation of involved chromosomes in meiosis.


A single chromosome undergoes two breaks and is reconstituted with the segment between the breaks inverted.

In this case, a break or breaks occur and that fragment of chromosome is inverted and rejoined rather than being lost. Inversions are thus rearrangements that do not involve loss of genetic material and, unless the breakpoints disrupt an important gene, individuals carrying inversions have a normal phenotype.

Paracentric: not involving centromere

Pericentric: involving centromere

Usually no abnormal phenotype

A inversion loop is formed between the pair of chromosomes and may lead to produce unbalanced gametes or offspring: producing various kinds of partial deletions and duplications.


Translocations are chromosomal abnormalities which occur when chromosomes break and the fragments rejoin to other chromosomes.

There are many structurally different types of translocations, some of which are discussed below. As with inversions, there is no loss of genetic material, although the breakpoint can cause disruption of a critical gene or juxtapose pieces of two genes to create a fusion gene that induces cancer. In general however, the problem with translocations occurs during meiosis and is manifest as reductions in fertility.

Reciprocal translocations

In a reciprocal translocation, two non-homologous chromosomes break and exchange fragments.

Individuals carrying such abnormalities still have a balanced complement of chromosomes and generally have a normal phenotype, but with varying degrees of subnormal fertility. The subfertility is caused by problems in chromosome pairing and segregation during meiosis.

Instead of having homologous chromosomes pair as bivalents, the translocation chromosomes and their homologs must form quadrivalents. Segregation in such a strange situation leads to formation of a number of genetically unbalanced gametes and hence, offspring with unbalanced genomes that are often lethal.

This is apparent when one thinks about the types of sperm that could be produced in a hypothetical male with a reciprocal translocation between chromosome 1 and 2, as illustrated below. Note that this one is a translocation heterozygote, having a normal chromosome 1 and 2 in addition to the translocation chromsomes.

The diagram has been simplified considerably by ignoring the crossovers that occurred during meiosis. In a real testis or ovary, the fraction of gametes that are unbalanced would depend upon how crossingover and segregation occured, which is influenced by factors such as the site of the translocated segments. The net result is considerable difficulty in predicting fertility of a translocation carrier. In general however, they show a substantial (often greater than 50%) reduction in fertility.

Some of the offspring of translocation carriers are cytogenetically normal, while others carry the translocation of their parent. Translocations are thus heritable and can be perpetuated in populations.

Centric Fusions (Robertsonian translocations)

A centric fusion is a translocation in which the centromeres of two acrocentric chromosomes fuse to generate one large metacentric chromosome. They are also often called Robertsonian translocations, although that term is used by purists to designate a very similar but distinct translocation in which one of the two centromeres is lost. The karyotype of an individual carrying a centric fusion has one less than the normal diploid number of chromosomes(45).

Meiosis in animals carrying a centric fusion chromosome involves formation of trivalents, which is certainly an abnormal structure. Considerable effort has gone into characterizing the effect of this type of translocation on fertility. In general, centric fusions appear to cause a mild reduction in fertility (5-15%), much less severe than in the case of reciprocal translocations.

Chromosome Diseases in Clinical

Autosomal Disease and Sex chromosomal Disease

Autosomal Disease

The general features in autosome abnormalities are a triad of growth retardation, mental retardation, and specific somatic abnormalities.

Down Syndrome (trisomy 21 syndrome)

Edwards Syndrome (trisomy 18 syndrome)

Patau Syndrome (trisomy 13 syndrome)

Cat Cry syndrome (5p- Syndrome)

Down Syndrome (trisomy 21 syndrome)

Down syndrome is the presence of three copies of chromosome 21 ,which occurs in one out of 600 to 800 babies.

Features include low muscle tone, a tendency to keep mouth open with a protrusion of the tongue, head and facial malformations such as a short small head with upwardly slanting eyelid folds, a depressed nasal bridge, a small nose, misshapen ears, narrow roof of the mouth, dental abnormalities, excessive skin on the back of the neck, and a relatively flat facial profile. People with Down Syndrome also have abnormalities of the extremities including unusually short arms, legs, and fingers, and unusual skin patterns. Affected individuals may also be short in stature, have poor coordination, metal retardation, as well as hearing impairment.

Sometimes Down Syndrome can be associated by structural malformations of the heart at birth, and increased chance of infectious disease including leukemia. These problems can potentially be life-threatening. Early death is also associated with Down Syndrome.

There are three different types of Down syndrome: Standard Trisomy 21, Mosaic and Unbalance Translocation.

Trisomy 21(92.5%)


Caused by meiotic non-disjunction of chromosome 21, correlated with age of mother.



Caused by mitotic non-disjunction of chromosome 21.

Unbalance Translocation(5%)

About five percent of all cases of trisomy 21 are due to Robertsonian Translocation. In this case, two breaks occur in separate chromosomes, usually the 14th and 21st or 21st and 22st chromosomes. There is rearrangement of the genetic material so that some of the 14th chromosome is replaced by extra 21st chromosome.

So while the number of chromosomes remains normal, there is a triplication of the 21st chromosome material. Some of these children may only have triplication of part of the 21st chromosome instead of the whole chromosome, which is called a partial trisomy 21.

Translocations resulting in trisomy 21 may be inherited, so it’s important to check the chromosomes of the parents in these cases to see if either may be a “carrier.”

Edwards Syndrome (trisomy 18 syndrome)

Ocurrence: 1 in 4000 ~ 5000 newborns

Karyotype: 47,XX(XY),+18(80%), 46,XX(XY)/ 47,XX(XY),+18(20%)

Feature: Common symptoms of Trisomy 18 include mental retardation and head and facial malformations including a prominent back portion of the head, malformed, low-set ears, a small jaw, a narrow roof of the mouth, an upturned nose, widely spaced eyes, narrow eyelid folds and drooping eye lids.  Overlapped, flexed fingers, webbing of the toes, and other foot malformations may also occur. Skeletal malformations include a small pelvis and short breastbone. Kidney and heart problems can also result and early death is associated.

Patau Syndrome (trisomy 13 syndrome)

Ocurrence: 1 in 5000 ~ 7000 newborns

Karyotype: 47,XX(XY),+13(80%); 46,XX(XY)/ 47,XX(XY),+18(5.9%); mosaicism.

Feature: Two commonly associated characteristics of Trisomy 13 are mental retardation sometimes stemming from incomplete brain development, and head and facial abnormalities including unusually small eyes, an abnormal groove in the upper lip (cleft lip), and incomplete closure of the roof of the mouth (cleft palate). Less common head and facial abnormalities include a relatively small head with sloping forehead, a broad flat nose, wide-set eyes, vertical skin folds covering the eyes, scalp defects, and malformed, low-set ears.

Those with Trisomy 13 may also have extra fingers of toes, kidney malformations, and structural heart defects. Generally, many infants with Trisomy 13 do not grow and gain weight at the expected rate threatening complications can develop during and life infancy early childhood.

Cat Cry syndrome (5p- Syndrome)

Ocurrence: 1 in 50000 newborns

Karyotype: 46,XX(XY),del(5)(p15)

Feature: It is characterized by a distinctive, high-pitched, catlike cry in infancy with growth failure, microcephaly, facial abnormalities, and mental retardation throughout life.

Sex chromosomal Disease

Change of sex chromosome also have the abnormalities and malformations of internal or external genital organs.

Turner Syndrome (45, X)

Klinefelter syndrome (47, XXY)

XYY syndrome (47, XYY)

Turner Syndrome

Ocurrence: 1 in 2500 liveborn females

Karyotype: 45,X

Feature: Short stature and lack of ovarian development are among the most common characteristics of Turner syndrome. Additionally, neck abnormalities including a webbed neck and low hairline can also occur. Skeletal disorders including scoliosis or curvature of the spine, dislocated hips, and elbows that turn out can also be characteristics. People with Turner syndrome are more likely to have certain health problems such as  osteoporosis, cardiovascular problems including constriction of the aorta and high blood pressure, and diabetes. Kidney and thyroid problems result in about 1/3 of the cases. It is also important to note that unlike Trisomy 13, Trisomy 18, and Down Syndrome, mental retardation is not associated with Turner Syndrome. In fact, there is no association between mental retardation and any sex chromosomal abnormality, indicating genes affecting mental development and ability lie only on autosomal chromosomes. Early death is also not associated with any of the sex linked chromosomal abnormalities.

Klinefelter syndrome

Ocurrence: 1 in 800 males; 1 in 100 mentally retarded males; 1 in 10 infertile males

Karyotype: 47,XXY

Feature: Characteristics normally associated with Klinefelter syndrome include being tall, sexually underdeveloped and infertile, though in some case testicular function is preserved. Sparse facial and body hair is also a common characteristic. Klinefelter’s can also cause delays in speech and motor skills as well as deficits in attention, auditory processing and social skills. Learning disabilities, anxiety, and depression can also result. Treatment for these problems includes testosterone therapy and assisted learning. Finally, people with Klinefelter’s have an increased chance of certain health problems including autoimmune disorders such as type II diabetes, breast cancer, osteoporosis, leg ulcers, depression, and dental problems.

XYY syndrome

Ocurrence: 1 in 750 ~ 1500 males;1 in 30 male prison populations

Karyotype: 47,XYY

Feature: People with XYY syndrome often appear physically normal for the first decade of life. As adults, people with XYY syndrome still appear relatively normal, although final height is approximately 7cm above average and there is also comparatively low weight relative to stature. Other common symptoms include larger craniofacial dimensions than those without the condition, severe acne in adolescence, increased physical activity, and behavior problems. Learning disabilities can also result, though mental retardation is not considered a symptom of XYY syndrome. While intelligence is usually within the normal range, IQ is 10 to 15 points lower than siblings’.


1. chromosomal disorders; trisomy; monosomy; mosaic; centric fusion

2. Causes of polyploidy; causes of aneuploidy.

3. What is the basis of structural aberration? Popular structural aberration?

4. Major karyotype of these disorders:

Down syndrome; Patau syndrome; Edwards syndrome; Cat Cry syndrome; Turner syndrome; Klinefelter syndrome; XYY syndrome.

5.The karyotype of a female is 45,XX,-21,-21,+t(21,21)(p11,q11). Is her phenotype normal or abnormal? If she and a normal male marry, can they procreate a normal baby? Why?

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