General Cytogenetics Information       Spanish Version


Chromosome 1 Ideogram
(Chromosome 1)

Chromosome 9 Ideogram
(Chromosome 9)

Chromosome 14 Ideogram
(Chromosome 14)

What Are Chromosomes?

Cytogenetics is the study of chromosomes and the related disease states caused by abnormal chromosome number and/or structure. Chromosomes are complex structures located in the cell nucleus, they are composed of DNA, histone and non-histone proteins, RNA , and polysaccharides. They are basically the "packages" that contain the DNA. Normally chromosomes can't be seen with a light microscope but during cell division they become condensed enough to be easily analyzed at 1000X. To collect cells with their chromosomes in this condensed state they are exposed to a mitotic inhibitor which blocks formation of the spindle and arrests cell division at the metaphase stage.

A variety of tissue types can be used to obtain chromosome preparations. Some examples include peripheral blood, bone marrow, amniotic fluid, and products of conception. Although specific techniques differ according to the type of tissue used, the basic method for obtaining chromosome preparations is as follows:

  • Sample log-in and initial setup.
  • Tissue culture (feeding and maintaining cell cultures).
  • Addition of a mitotic inhibitor to arrest cells at metaphase.
  • Harvest cells. This step is very important in obtaining high quality preparations. It involves exposing the cells to a hypotonic solution followed by a series of fixative solutions. This causes the cells to expand so the chromosomes will spread out and can be individually examined.
  • Stain chromosome preparations to detect possible numerical and structural changes.

Chromosome Morphology

Under the microscope chromosomes appear as thin, thread-like structures. They all have a short arm and long arm separated by a primary constriction called the centromere. The short arm is designated as p and the long arm as q. The centromere is the location of spindle attachment and is an integral part of the chromosome. It is essential for the normal movement and segregation of chromosomes during cell division. Human metaphase chromosomes come in three basic shapes and can be categorized according to the length of the short and long arms and also the centromere location. Metacentric chromosomes have short and long arms of roughly equal length with the centromere in the middle. Submetacentric chromosomes have short and long arms of unequal length with the centromere more towards one end. Acrocentric chromosomes have a centromere very near to one end and have very small short arms. They frequently have secondary constrictions on the short arms that connect very small pieces of DNA, called stalks and satellites, to the centromere. The stalks contain genes which code for ribosomal RNA.

The diagrams to the left, called ideograms*, of G-banded chromosomes 1, 9, and 14 are typical examples of metacentric, submetacentric, and acrocentric chromosomes respectively. The ideogram is basically a "chromosome map" showing the relationship between the short and long arms, centromere (cen), and in the case of acrocentric chromosomes the stalks (st) and satellites (sa). The specific banding patterns are also illustrated. Each band is numbered to aid in describing rearrangements.

Chromosome Analysis

Virtually all routine clinical Cytogenetic analyses are done on chromosome preparations that have been treated and stained to produce a banding pattern specific to each chromosome. This allows for the detection of subtle changes in chromosome structure. The most common staining treatment is called G-banding. A variety of other staining techniques are available to help identify specific abnormalities. Once stained metaphase chromosome preparations have been obtained they can be examined under the microscope. Typically 15-20 cells are scanned and counted with at least 5 cells being fully analyzed. During a full analysis each chromosome is critically compared band-for-band with it's homolog. It is necessary to examine this many cells in order to detect clinically significant mosaicism (see below).

Following microscopic analysis, either photographic or computerized digital images of the best quality metaphase cells are made. Each chromosome can then be arranged in pairs according to size and banding pattern into a karyotype. The karyotype allows the Cytogeneticist to even more closely examine each chromosome for structural changes. A written description of the karyotype which defines the chromosome analysis is then made.

*Ideograms courtesy of Tim Knight, Fred Hutchinson Cancer Research Center, Seattle, WA.


Normal Chromosomes

Normal human somatic cells have 46 chromosomes: 22 pairs, or homologs, of autosomes (chromosomes 1-22) and two sex chromosomes. This is called the diploid number. Females carry two X chromosomes (46,XX) while males have an X and a Y (46,XY). Germ cells (egg and sperm) have 23 chromosomes: one copy of each autosome plus a single sex chromosome. This is referred to as the haploid number. One chromosome from each autosomal pair plus one sex chromosome is inherited from each parent. Mothers can contribute only an X chromosome to their children while fathers can contribute either an X or a Y.

Chromosome Abnormalities

Although chromosome abnormalities can be very complex there are two basic types: numerical and structural. Both types can occur simultaneously.

Numerical abnormalities involve the loss and/or gain of a whole chromosome or chromosomes and can include both autosomes and sex chromosomes. Generally chromosome loss has a greater effect on an individual than does chromosome gain although these can also have severe consequences. Cells which have lost a chromosome are monosomy for that chromosome while those with an extra chromosome show trisomy for the chromosome involved. Nearly all autosomal monosomies die shortly after conception and only a few trisomy conditions survive to full term. The most common autosomal numerical abnormality is Down Syndrome or trisomy-21. Trisomies for chromosomes 13 and 18 may also survive to birth but are more severely affected than individuals with Down Syndrome. Curiously, a condition called triploidy in which there is an extra copy of every chromosome (69 total), can occasionally survive to birth but usually die in the newborn period.

Another general rule is that loss or gain of an autosome has more severe consequences than loss or gain of a sex chromosome. The most common sex chromosome abnormality is monosomy of the X chromosome (45,X) or Turner Syndrome. Another fairly common example is Klinefelter Syndrome (47,XXY). Although there is substantial variation within each syndrome, affected individuals often lead fairly normal lives.

Occasionally an individual carries an extra chromosome which can't be identified by it's banding pattern, these are called marker chromosomes. The introduction of FISH techniques has been a valuable tool in the identification of marker chromosomes.

Structural abnormalities involve changes in the structure of one or more chromosomes. They can be incredibly complex but for the purposes of this discussion we will focus on the three of the more common types:

  • Deletions involve loss of material from a single chromosome. The effects are typically severe since there is a loss of genetic material.

  • Inversions occur when there are two breaks within a single chromosome and the broken segment flips 180 (inverts) and reattaches to form a chromosome that is structurally out-of-sequence. There is usually no risk for problems to an individual if the inversion is of familial origin (has been inherited from a parent.) There is a slightly increased risk if it is a de novo (new) mutation due possibly to an interruption of a key gene sequence. Although an inversion carrier may be completely normal, they are at a slightly increased risk for producing a chromosomally unbalanced embryo. This is because an inverted chromosome has difficulty pairing with it's normal homolog during meiosis, which can result in gametes containing unbalanced derivative chromosomes if an unequal cross-over event occurs.

  • Translocations involve exchange of material between two or more chromosomes. If a translocation is reciprocal (balanced) the risk for problems to an individual is similar to that with inversions: usually none if familial and slightly increased if de novo. Problems arise with translocations when gametes from a balanced parent are formed which do not contain both translocation products. When such a gamete combines with a normal gamete from the other parent the result is an unbalanced embryo which is partially monosomic for one chromosome and partially trisomic for the other.
Numerical and structural abnormalities can be further divided into two main categories: constitutional, those you are born with; and acquired, those that arise as secondary changes to other diseases such as cancer.

Sometimes individuals are found who have both normal and abnormal cell lines. These people are called mosaics and in the vast majority of these cases the abnormal cell line has a numerical chromosome abnormality. Structural mosaics are extremely rare. The degree to which an individual is clinically affected usually depends on the percentage of abnormal cells. A routine Cytogenetic analysis typically includes the examination of at least 15-20 cells in order to rule out any clinically significant mosaicism.

These are just some of the more common abnormalities encountered by a Cytogenetic Laboratory. Because the number of abnormal possibilities is almost infinite, a Cytogeneticist must be trained to detect and interpret virtually any chromosome abnormality that can occur.

Examples of Chromosome Abnormalities

Click on any of the following links to see some examples of numerical and structural chromosome abnormalities:
  • Example 1:  Down Syndrome, a common numerical abnormality.
  • Example 2:  An inversion in chromosome 10.
  • Example 3:  An interstitial deletion of chromosome 16.
  • Example 4:  A translocation between chromosomes 2 and 15.
  • Example 5:  A translocation between chromosomes 5 and 8.
  • Example 6:  A subtle inversion in chromosome 3.
  • Example 7:  An interstitial deletion of chromosome 7.
  • Example 8:  An unbalanced translocation between chromosomes 13 and 14.

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