Chromosome Abnormality

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Chromosome abnormalities fall into one of two categories: numerical or structural. These are not mutually exclusive: that is, numerical and structural abnormality may be present at the same time. Numerical abnormality, referred to as "aneuploidy", can be due to whole chromosome number change (having too many chromosomes or too few) or can be due to altered copy number of parts of chromosomes. Structural abnormalities are changes that alter the content of chromosomes. Structural changes are referred to as deletions (chromosomal material is missing), insertions (additional chromosomal material is present), inversions (a portion of the chromosome is 'backwards'), and translocations (chromosomal material has moved from one chromosome to another). Structural abnormalities can occur spontaneously, or they may be induced by agents, such as chemicals, ionizing radiation, or viral infections.

Errors detected by fetal monitoring tests usually have occurred when eggs or sperm are formed, or during the early developmental stages of the fetus. The age of the mother and certain environmental factors can increase the risk of a fetal abnormal chromosome number.



As a rule, the cells of all organisms contain a constant number of chromosomes that have maintained a constant structure throughout development. Major exceptions to this rule include gametes produced by meiosis (egg and sperm cells contain a reduced number of chromosomes), and cell types in which a change in chromosome number or structure is necessary for function (immune cells generate a large antibody repertoire using chromosome rearrangement). These exceptions occur only in specialized cell types, and reflect changes made to the original chromosomal content of an individual organism which is set at fertilization.

Humans, like all other sexually reproducing organisms, receive one copy of each chromosome from each parent at conception (i.e. fertilization). Specifically, an egg contains 23 from the mother (chromosomes 1 through 22, and X), and a sperm contains 23 from the father (chromosomes 1 through 22, and either X or Y). When the egg and sperm fuse at conception, a new individual is created containing 46 chromosomes, the expected number for a human individual. Growth during development occurs by mitosis to generate a fetus, then child, then adult. In every cell division, each chromosome is faithfully duplicated and one of each duplicate pair is delivered to each of the daughter cells. This process generates daughter cells with exactly the same chromosomal content as the original cell.

Every process has an error rate, and human meiosis and mitosis are not exceptions. Changes in the expected number or structure of chromosomes do occur, and many such changes are observed in people. These changes may or may not be associated with heritable traits we recognize as syndromes or diseases. However, many well-described abnormalities are because the syndrome or disease characteristics provided a motivation for study. Some commonly observed abnormalities and associated consequences are described below. cc

Abnormalities of Chromosome Number

Trisomy is a type of anueploidy in which there are three copies of a particular chromosome instead of the regular two. Trisomy for most chromosomes is not compatible with life. The most common and recognized type of trisomy is trisomy 21, or Down syndrome. Like the name suggests, in persons with Down syndrome there are three copies of chromosome 21 instead of the regular pair. Below is a depiction of a karyotype, or a picture of the chromosomes in a single cell, of a person with trisomy 21:


Monsomy is another type of aneuploidy where there is one copy of a certain chromosome instead of the regular two copies. When this occurs it is almost always lethal. The only complete monosomy that is compatible with life is Turner syndrome, where there is only one X chromosome instead of the normal pair. Below is a depiction of a karyotype of a person with Turner syndrome:

Monosomy JPEG.jpg

The most common cause of aneuploidy is something called nondisjunction. Nondisjunction is an error in cell division during production of the germline cells, which are the eggs and sperm. The germline cells differ from the other cells in the body because, instead of having two sets of 23 chromosomes (for a total of 46), they have one set of 23 chromosomes. This makes sense because normally when the egg and the sperm come together, the resulting zygote or baby will have one set of 23 chromosomes from the mother and one set of 23 chromosomes from the father, for a total of 46 chromosomes in each cell.

To produce germ cells with 23 chromosomes, cells in the ovary and testes with 46 chromosomes undergo two seperate cell divisions called Meiosis I and Meiosis II. In meiosis, a single copy of each of the 23 pairs of chromosomes is randomly distributed to each of the resulting germcells. When nondisjunction occurs, the chromosomes do not segregate properly during one of these cell divisions, so that one of the resulting daughter cells may end up with too many chromosomes while another may end up with two few. The origin of the extra chromosome depends on when the nondisjunction occurs in the cell division process. If nondisjunction happens in the earlier division, or Meiosis I, the resulting germline cell will have 2 different copies of a certain chromosome, one that was inherited from that individual's mother and one from their father (the future embryo's grandmother and grandfather), instead of a single copy of the chromosome. If nondisjunction happens in the subsequent cell division, or Meiosis II, the resulting germline cell will have 2 identical copies of a certain chromosome that may have been inherited either from that person's mother or from their father.

Abnormalities of Chromosome Structure

Abnormalities of chromosome structure can be either unbalanced or balanced rearrangements. If the rearrangement is unbalanced, there is additional or missing genetic material, a situation that often results in a disease. On the other hand, if the rearrangement is balanced, there is no extra or missing chromosome material. Balanced rearrangements are not uncommon in "normal" individuals, although there is a significant chance that they may pass an unbalanced rearrangement that could cause birth defects to their children or, if the defect is severe enough, the balanced rearrangement could cause infertility. Balanced rearrangements may themselves cause problems in individuals who carry them. This occurs when the rearrangement interrupts a gene or affects the expression of a gene.

The types of unbalanced rearrangements are deletions, duplications, marker or ring chromosomes, and isochromosomes.

Chromosome Deletions A chromosome deletion is when part of a chromosome segment is lost, resulting in chromosome imbalance. A deletion can occur on any chromosome, at any place on the chromsome, and it may be a large deletion or a small deletion. The implications of this deletion depends on how big the deletion is, and what genes are now missing due to the deletion.

Chromosome Duplications A chromosome duplication is when a section of a chromosome is in duplicate. This means that the person with the duplication actually has 3 copies of a particular piece of DNA, rather than the normal 2. Sometimes the extra piece of genetic material is on the chromosome on which it's normally found, and other times it's on a different chromosome. In general, duplications are less harmful than deletions; however, the extra genetic material can cause birth defects and health problems.

Marker and Ring Chromosomes A marker chromosome is a very small, unidentified chromosome that can be seen on a karyotype. Individuals with marker chromosomes usually have this marker chromosome in addition to the normal 46 chromosomes. Marker chromosomes are very difficult to identify, and as a result their clinical significance is difficult to assess. With marker chromosomes there is a risk for fetal abnormality, which ranges from a very low risk to a risk of 100%.

Ring chromosomes are rare, but can occur in any chromosome. Ring chromosomes form when a chromosome undergoes 2 breaks, and these broken ends stick back together. This sticking back together can occur with no loss of genetic information, or it may occur with a loss of genetic information. Ring chromosomes often cause problems during cell division, which in turn causes health problems in individuals. The size of the ring, how much genetic material is lost, and which chromosome and genes are involved all determine the consequences of ring chromosomes.

Isochromosomes An isochromosome is when one arm of a chromosome is missing, and the other arm is duplicated. A person with 46 chromosomes containing an isochromosome has a single copy of one arm, and three copies of the other arm.

The types of balanced rearrangments are inversions (paracentric or pericentric), and translocations (reciprocal or Robertsonian).

Inversions An inversion consists of two breaks in one chromosome. The area between the breaks is inverted (turned around), and then reinserted and the breaks then unite to the rest of the chromosome. If the inverted area includes the centromere it is called a pericentric inversion. If it does not, it is called a paracentric inversion.

Periinv.jpg Parainv.jpg

Notice that in a pericentric inversion one break is in the short arm and one in the long arm. Therefore an example of a cytogenetic nomenclature might read 46,XY,inv(3)(p23q27). A paracenteric inversion does not include the centromere and an example might be 46,XY,inv(1)(p12p31).

When a parent has an inversion there is an increased risk for offspring with an incorrect amount of genetic material. This can lead to babies with birth defects and/or abnormal development or an increased risk for miscarriage. The possible pregnancy outcomes for an individual with an inversion is rather complicated and depends on how big the inversion is, where it is, and what type of inversion is present, paracentric or pericentric. There are many inversions that occur in the general population that are called normal variants. Including Inv(9) and Inv(2). These inversions are not related to an increased risk of birth defects and/or developmental difficulties.



Translocations can be a little tricky. Above is an example of a balanced translocation. The long arms of chromosome 7 and 21 have broken off and switched places. So you can see a normal 7 and 21, and a translocated 7 and 21. This individual has all the material needed, just switched around (translocated), so they should have no health problems, because it is 'balanced'. However there can be a problem when this person has children.

Remember that when the egg or sperm is made, each parent gives one of each chromosome pair. What would happen if this person gave the normal seven and the 21p with 7q attached? Look below:


There is an extra copy of 7q. If you count them you will find three copies of 7q instead of two. And there is only one copy of 21q. Therefore this is 'unbalanced', there is extra and missing information that can lead to birth defects, cognitive abnormalities, and an increased risk for miscarriage. For many unbalanced rearrangements it is not possible to predict what abnormalities to expect.

Robertsonian Translocation - This type of rearrangement involves two acrocentric chromosomes that fuse near the centromere region with loss of the short arms. An acrocentric chromosome is a type of chromosome with the centromere near one end (in humans these are chromosomes 13, 14, 15, 21 and 22). The resulting balanced karyotype has only 45 chromosomes, including the translocation chromosome, which, in effect, is made up of the long arms of two chromosomes. The most common are 13q14q and 14q;21q. The translocation involving 13q and 14q is found in about 1 person in 1300.

Reciprocal Translocation - A reciprocal translocation involves the breakage of nonhomologous chromosomes, with reciprocal or even exchange of the broken-off segments. Usually only two chromosomes are involved and the total chromosome number is unchanged. Reciprocal translocations are relatively common (1/600 newborns) and are usually harmless. Like other balanced balanced structural rearrangements, they are associated with a high risk of unbalanced gametes and abnormal progeny. Balanced translocations are more commonly found in couples who have had two or more spontaneous abortions and in infertile males than in the general population.


Most of the time when a person has a chromosome anomaly, the same anomaly is present in every cell. However, sometimes a person will have different chromosome constitutions depending on which cell is being examined (usually there are only two different constitutions). Most of the differences are numeral, although structural differences can occur. For example, this may mean a person has 47 chromosomes in 1/2 of their cells and the normal 46 chromosomes in the other half. This is known as mosiacism.

Mosaicism most commonly occurs after a non-disjunction event during an early post-zygotic mitotic division. For example, a zygote with 47 chromosomes (ex: trisomy 18) may loose the extra chromosome during one of the early divisions and some cells would differ numerically from other cells. The effects the mosaicism has on development depends on the timing of the non-disjunction event, the chromosome anomaly, the fraction of the body's cell's that are carrying the anomaly, and the tissues affected. It's often difficult to discern what the effects of a discovered mosaicism (especially if it's detected prenatally) due to the impossibility of ascertaining accurate information of the above mentioned influences.

Although studies of individuals with mosaicism often do not include the most subtly affected individuals (because these individuals often do not present clinically), it's generally thought a person with a mosaic form of a known disease may be affected less severely than those who have the genetic anomaly in all of their cells.

In the lab, cytogeneticists work to distinguish true mosiacism (which is a reflection of the individual's chromosomes) and psuedomosiacism, which is a type of mosiacism which is only present in some of the cultured cells (the non-disjunction event occurred during culture, and thus, does not pose a threat to development), rather than being reflective of the individual's true chromosomal constitution.

Genomic imprinting and Uniparental disomy

Genomic imprinting can be defined as the phenomenon in which expression of alleles is influenced by chemical changes to the DNA, such as covalent modification or methylation, and not changes to the sequence itself. Genomic imprinting is a reversible type of gene inactivation because it does not change the sequence, but rather slightly modifies the DNA's chemistry in a way that can be undone.

Uniparental disomy occurs when both chromosomes, or portions of both chromosomes, originated from a single parent, rather than having contributions from both the mom and the dad. If the two identical chromosomes (ex: both from mom) are present, this is called isodisomy. This phenomenon occurs in 3-5% of individuals with Angelman syndrome. In their case, two copies of the paternal chromosome 15 are present.


Testing can be performed to examine the chromosomes of the fetus. The two types of testing available are Amniocentesis and Chorionic Villus Sampling. In both cases, some cells from the fetus are grown and processed in the laboratory so that the chromosomes can be studied. Pictures of the chromosomes viewed under a microscope are taken and the chromosomes are then arranged by size and paired together. The picture of the arranged chromosomes is known as a karyotype, as seen above. The karyotype is evaluated for size and structure of the chromosomes.


Chromosome Deletion Outreach, Inc. 1996-2007. Introduction to Chromosomes.

Genetic Alliance. 2007. Understanding Genetics: A Guide for Patients and Health Care Professionals.

National Human Genome Research Institute. 2007.

Nussbaum et al Genetics in Medicine (Edition 7.0), Saunders 2007

Rubin E., Farber J.L. [1999]. Pathology [3rd ed., p. 225]. Philadelphia: Lippincott-Raven)

See Also

More on genes and chromosomes:

Specific Conditions:

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