The following chromosome studies may help to determine whether a child has a genetic birth defect:
Karyotype. The chromosomes need to be stained in order to see them with a microscope. When stained, the chromosomes look like strings with light and dark "bands." A picture (an actual photograph from one cell) of all 46 chromosomes, in their pairs, is called a "karyotype." A normal female karyotype is written 46, XX, and a normal male karyotype is written 46, XY. The standard analysis of the chromosomal material evaluates both the number and structure of the chromosomes, with a very high accuracy. Chromosome analyses are usually done from a blood sample (white blood cells), prenatal specimen, skin biopsy, or other tissue sample. Chromosomes are analyzed by specially trained health care personnel that have advanced degrees in cytogenetic technology and genetics. "Cytogenetics" is a word to describe the study of chromosomes.
In a karyotype, the chromosomes can look bent or twisted. This is normal and is a result of how they were sitting on the slide when the photograph was taken. Chromosomes are flexible structures that condense and elongate during different stages of cell division. If you unraveled all of the DNA that makes up the 46 chromosomes, you would find over 7 feet of DNA from one single cell.
Extended banding chromosome studies. Extended banding or "high resolution" chromosome studies means that the chromosomes are studied at a higher resolution than the standard chromosome analysis mentioned above. The chromosomes are prepared in such a way that they are a little longer, so that more bands can be seen. This allows you to see smaller pieces of the chromosome, so that you could identify smaller structural chromosome abnormalities not visible on a routine analysis.
Fluorescence in situ hybridization (FISH). FISH is a laboratory technique used to determine how many copies of a specific segment of DNA are present in a cell. It is also used to identify structurally-abnormal chromosomes. In the lab, a segment of DNA is chemically modified and labeled so that it will look fluorescent (very brightly colored) under a special microscope. This DNA is called a "probe." Probes can find matching segments of DNA when added to cells under certain conditions.
For example, if a baby is suspected of having trisomy 21 Down syndrome and an amniocentesis is done on the pregnancy, a FISH study can be performed on the cells found in the amniotic fluid. A probe made for chromosome #21 can determine how many copies of the #21 chromosome the baby has. Under a special microscope, the cells from a baby with trisomy 21 would contain three "signals" or three brightly colored areas, where the probe matched up with the three #21 chromosomes. A FISH study does not replace a chromosome study, but is done in addition to a standard chromosome study, depending on the birth defect in question.
FISH can be used to detect structural chromosome abnormalities (such as submicroscopic deletions) that are beyond the resolution of extended banding chromosome studies.
"Telomere" is a term used to describe the very ends of chromosomes. When FISH is used specifically to look for chromosome abnormalities in this area, it is referred to as "subtelomeric FISH testing."
Chromosomal microarray analysis (CMA). CMA is a new laboratory test used to detect chromosomal imbalance at a higher resolution than current standard chromosome or FISH techniques.
A sample of DNA from the individual to be tested and a control DNA sample are arranged in a particular order (array) on a glass slide. Fluorescent dyes are attached to the DNA samples. These slides are then placed in a special scanner that measures the brightness of each fluorescent area.
This process looks for identification of a change in DNA copy number. These changes in DNA copy number may represent changes seen in the general population that do not cause genetic diseases. However, some changes in copy number may indicate a chromosomal abnormality, such as a chromosomal imbalance, loss, or gain. Types of chromosomal abnormalities may include small chromosomal rearrangements, small duplications of chromosomal material (trisomy), or small deletion of chromosomal material (monosomy).