Structural abnormalities are not as commonly seen or identified as trisomies or monosomies, but they can be every bit as serious. The expression of structural chromosomal abnormalities is vast. Some, in fact, may be beneficial. One such example is sickle cell disease SCD caused by a defect on chromosome While inheriting two of these chromosomes will lead to SCD, having just one can protect you against malaria.
Other defects are believed to provide protection against HIV, stimulating the production of broadly neutralizing HIV antibodies BnAbs in a rare subset of infected people.
When used for prenatal screening, karyotypes are typically performed during the first trimester and again in the second trimester. The standard panel tests for 19 different congenital diseases, including Down syndrome and cystic fibrosis. Karyotypes are sometimes used for preconception screening under specific conditions, namely:. Karyotyping is not used for routine preconception screening but rather for couples whose risk is considered high.
Examples include Ashkanzi Jewish couples who are at high risk of Tay-Sachs disease or African American couples with a family history of sickle cell disease. Couples who are either unable to conceive or experience recurrent miscarriage may also undergo parental karyotyping if all other causes have been explored and excluded.
Finally, a karyotype may be used to confirm chronic myeloid leukemia in association with other tests. The presence of the Philadelphia chromosome on its own cannot confirm the cancer diagnosis.
A karyotype can theoretically be performed on any body fluid or tissue, but, in clinical practice, samples are obtained in four ways:. After the sample is collected, it is analyzed in a lab by a specialist known as a cytogeneticist.
The process begins by growing the collected cells in a nutrient-enriched media. Doing so helps pinpoint the stage of mitosis in which the chromosomes are most distinguishable. The cells are then placed on a slide, stained with a fluorescent dye, and positioned under the lens of an electron microscope.
The cytogeneticist then takes microphotographs of the chromosomes and re-arranges the images like a jigsaw puzzle to correctly match the 22 pairs of autosomal chromosomes and two pairs of sex chromosomes. Once the images are correctly positioned, they are evaluated to determine whether any chromosomes are missing or added. The staining can also help reveal structural abnormalities, either because the banding patterns on the chromosomes are mismatched or missing, or because the length of a chromosomal "arm" is longer or shorter than another.
Any abnormality will be listed on a karyotype report by the chromosome involved and the characteristics of the abnormality.
These findings will be accompanied by "possible," "likely," or "definitive" interpretations. Some conditions can be definitively diagnosed with a karyotype; others cannot. Results from a prenatal karyotype take between 10 and 14 days. Others are usually ready within three to seven days. While your healthcare provider will usually review the results with you, a genetic counselor may be on-hand to help you better understand what the results mean and do not mean.
This is especially important if a congenital disorder is detected or preconception screening reveals an increased risk of an inheritable disease if you have a baby. Sign up for our Health Tip of the Day newsletter, and receive daily tips that will help you live your healthiest life. American College of Obstetricians and Gynecologists. Prenatal Genetic Diagnostic Tests. Today, most karyotypes are stained with Giemsa dye, which offers better resolution of individual bands, produces a more stable preparation, and can be analyzed with ordinary bright-field microscopy.
The molecular causes for staining differences along the length of a chromosome are complex and include the base composition of the DNA and local differences in chromatin structure. In G-banding , the variant of Giemsa staining most commonly used in North America, metaphase chromosomes are first treated briefly with trypsin, an enzyme that degrades proteins, before the chromosomes are stained with Giemsa.
Trypsin partially digests some of the chromosomal proteins, thereby relaxing the chromatin structure and allowing the Giemsa dye access to the DNA. In general, heterochromatic regions, which tend to be AT-rich DNA and relatively gene-poor, stain more darkly in G-banding. In contrast, less condensed chromatin—which tends to be GC-rich and more transcriptionally active—incorporates less Giemsa stain, and these regions appear as light bands in G-banding.
Most importantly, G-banding produces reproducible patterns for each chromosome, and these patterns are shared between the individuals of a species. An example of Giemsa-stained human chromosomes, as they would appear under a microscope, is shown in Figure 1a. Typically, Giemsa staining produces between and bands distributed among the 23 pairs of human chromosomes.
Measured in DNA terms, a G-band represents several million to 10 million base pairs of DNA, a stretch long enough to contain hundreds of genes.
G-banding is not the only technique used to stain chromosomes, however. R-banding, which is used in parts of Europe, also involves Giemsa stain, but the procedure generates the reverse pattern from G-banding. In R-banding Figure 1c , the chromosomes are heated before Giemsa stain is applied.
The heat treatment is thought to preferentially melt the DNA helix in the AT-rich regions that usually bind Giemsa stain most strongly, leaving only the comparatively GC-rich regions to take up the stain. R-banding is often used to provide critical details about gene-rich regions that are located near the telomeres.
Yet another method is C-banding Figure 1d , which can be used to specifically stain constitutive heterochromatin , or genetically inactive DNA, but it is rarely used for diagnostic purposes these days. C-banding is a specialized Giemsa technique that primarily stains chromosomes at the centromeres, which have large amounts of AT-rich satellite DNA.
The first method to be used to identify all 46 human chromosomes was Q-banding Figure 1b , which is achieved by staining the chromosomes with quinacrine and examining them under UV light. This method is most useful for examining chromosomal translocations, especially ones involving the Y chromosome.
Taken together, these banding techniques offer clinical cytogeneticists an arsenal of staining methods for diagnosing chromosomal abnormalities in patients.
In order to maximize the diagnostic information obtained from a chromosome preparation, images of the individual chromosomes are arranged into a standardized format known as a karyotype, or more precisely, a karyogram Figure 1a-c. According to international conventions, human autosomes, or non-sex chromosomes, are numbered from 1 to 22, in descending order by size, with the exceptions of chromosomes 21 and 22, the former actually being the smallest autosome.
The sex chromosomes are generally placed at the end of a karyogram. Within a karyogram, chromosomes are aligned along a horizontal axis shared by their centromeres.
Individual chromosomes are always depicted with their short p arms—p for "petite," the French word for "small"—at the top, and their long q arms—q for "queue"—at the bottom. Centromere placement can also be used to identify the gross morphology, or shape, of chromosomes. For example, metacentric chromosomes, such as chromosomes 1, 3, and 16, have p and q arms of nearly equal lengths.
Submetacentric chromosomes, such as chromosomes 2, 6, and 10, have centromeres slightly displaced from the center. Acrocentric chromosomes, such as chromosomes 14, 15, and 21, have centromeres located near their ends.
Arranging chromosomes into a karyogram can simplify the identification of any abnormalities. Note that the banding patterns between the two chromosome copies, or homologues, of any autosome are nearly identical.
Some subtle differences between the homologues of a given chromosome can be attributed to natural structural variability among individuals. Occasionally, technical artifacts associated with the processing of chromosomes will also generate apparent differences between the two homologues, but these artifacts can be identified by analyzing 15—20 metaphase spreads from one individual.
It is highly unlikely that the same technical artifact would occur repeatedly in a given specimen. Today, G-banded karyograms are routinely used to diagnose a wide range of chromosomal abnormalities in individuals. Although the resolution of chromosomal changes detectable by karyotyping is typically a few megabases, this can be sufficient to diagnose certain categories of abnormalities.
For example, aneuploidy , which is often caused by the absence or addition of a chromosome, is simple to detect by karyotype analysis. Cytogeneticists can also frequently detect much more subtle deletions or insertions as deviations from normal banding patterns. Likewise, translocations are often readily apparent on karyotypes.
When regional changes in chromosomes are observed on karyotypes, researchers often are interested in identifying candidate genes within the critical interval whose misexpression may cause symptoms in patients. This search process has been greatly facilitated by the completion of the Human Genome Project , which has correlated cytogenetic bands with DNA sequence information. Consequently, investigators are now able to apply a range of molecular cytogenetic techniques to achieve even higher resolution of genomic changes.
Fluorescence in situ hybridization FISH and comparative genomic hybridization CGH are examples of two approaches that can potentially identify abnormalities at the level of individual genes. Molecular cytogenetics is a dynamic discipline, and new diagnostic methods continue to be developed. As these new technologies are implemented in the clinic, we can expect that cytogeneticists will be able to make the leap from karyotype to gene with increasing efficiency.
Caspersson, T. Differential banding of alkylating fluorochromes in human chromosomes. Experimental Cell Research 60 , — doi Gartler, S.
The chromosome number in humans: A brief history. Nature Reviews Genetics 7 , — doi Speicher, M. Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nature Genetics 12 , — link to article. Strachan, T. Human Molecular Genetics , 2nd ed. Wiley, New York, Tjio, J. This usually goes away in a few days. Your health care provider may recommend or prescribe a pain reliever to help. If your results were abnormal not normal, it means you or your child has more or fewer than 46 chromosomes, or there is something abnormal about the size, shape, or structure of one or more of your chromosomes.
Abnormal chromosomes can cause a variety of health problems. The symptoms and severity depend on which chromosomes have been affected. If you were tested because you have a certain type of cancer or blood disorder, your results can show whether or not your condition is caused by a chromosomal defect. These results can help your health care provider make the best treatment plan for you.
Learn more about laboratory tests, reference ranges, and understanding results. If you are thinking about getting tested or have received abnormal results on your karyotype test, it may help to speak to a genetic counselor. A genetic counselor is a specially trained professional in genetics and genetic testing. He or she can explain what your results mean, direct you to support services, and help you make informed decisions about your health or the health of your child.
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health. Karyotype Genetic Test. What is a karyotype test? Other names: genetic testing, chromosome testing, chromosome studies, cytogenetic analysis.
What is it used for? A karyotype test may be used to: Check an unborn baby for genetic disorders Diagnose a genetic disease in a baby or young child Find out if a chromosomal defect is preventing a woman from getting pregnant or is causing miscarriages Check a stillborn baby a baby that died late in pregnancy or during birth to see if a chromosomal defect was the cause of death See if you have a genetic disorder that could be passed along to your children Diagnose or make a treatment plan for certain types of cancer and blood disorders.
Why do I need a karyotype test? These include: Your age. The overall risk of genetic birth defects is small, but the risk is higher for women who have babies at age 35 or older. Family history. What happens during a karyotype test?
The most common ways to get a sample include: A blood test. For this test, a health care professional will take a blood sample from a vein in your arm, using a small needle. After the needle is inserted, a small amount of blood will be collected into a test tube or vial. You may feel a little sting when the needle goes in or out. This usually takes less than five minutes. Prenatal testing with amniocentesis or chorionic villus sampling CVS. Chorionic villi are tiny growths found in the placenta.
For amniocentesis: You'll lie on your back on an exam table. Your provider will move an ultrasound device over your abdomen.
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