Modern genetic testing is based upon an ever-expanding knowledge of the structure of human chromosomes, the DNA sequence of the genes on these chromosomes, and how specific variations in the sequence of particular regions of DNA are associated with the occurrence of a specific disease. Over the last 50 years, the ability to identify mutations in DNA has completely altered both the manner and the time required to verify the presence of specific mutations. However, there are important considerations to be applied in the evaluation of these tests.
Genetic Analysis by Karyotyping
In its earliest form, genetic testing did not examine individual genes or their specific DNA, but rather looked at the overall structure of the 23 pairs of human chromosomes (humans have what are known as 22 pairs of "autosomes" and 1 pair of sex chromosomes, the X and Y) through a technique known as karyotype analysis. Just before a human cell divides, the chromosomal DNA will condense and the chromosomes align. This is the only time during the cell’s life cycle when the chromosomes can be visualized using certain stains and a light microscope. Each of the chromosomes has a specific size and appearance when stained and once they are photographed their structure can be analyzed.
Karyotype analysis is rather limited in that it can only be used to identify either major structural alterations in individual chromosomes or the inappropriate presence of extra chromosomes. This occurs in conditions such as Down syndrome (where there is an entire extra copy of chromosome 21 or a duplication of a major portion of the chromosome) or in sex chromosome based syndromes such as Klinefelter’s syndrome or Turner's syndrome (where there are alterations in the number and/or structure of the X chromosome) or the so-called “Philadelphia chromosome” which occurs in some forms of leukemia.
Genetic Analysis by DNA Amplification
With the advent of the method known as the “polymerase chain reaction” (or PCR), DNA testing for genetic changes has changed dramatically. The human genome project has provided DNA sequence information for all of the 25 to 30,000 genes that are present in a human cell. There are normal variations in DNA sequences of genes (all humans are different clearly), but there are also pathologic or disease-causing changes in genetic sequences. With PCR, a minute amount of chromosomal DNA can be subjected to an enzymatic reaction that will yield tens of millions of copies of a specific DNA sequence. Using this method, known disease-causing changes in the DNA sequence of a specific gene can be identified at the molecular level.
Genes and Disease
At the DNA level, it is important to remember that there are actually a limited number of diseases that are absolutely caused because of changes in the DNA sequence of a specific single gene. Some of these include disorders such as sickle cell anemia, hemochromatosis, and cystic fibrosis. With advances in understanding the genetics of specific diseases, it is more likely the case that alterations in a specific gene may increase the risk of developing a disorder, but they do not guarantee that it will appear. Some examples of this include mutations in the BRCA1 gene that are associated with a heightened risk of developing breast and ovarian cancer, or changes in the gene for neuregulin-1 that are associated with an increased risk for schizophrenia.
As the number and quality of studies aimed at identifying changes in specific genes that are linked to disease development grows, modern medicine and science will be better able to determine the influence that changes in a given set of genes has on the later development of specific disorders and what steps can be taken to prevent their occurrence.
Read more about trisomy 21 and Down syndrome at ds-health. Learn more about BRCA1 mutations at the US National Cancer Institute (NCI). Visit the genetic home reference at the US National Library of Medicine (NLM) to learn more about chromosomes and karyotype analysis.
Always speak with your healthcare provider to learn about disease development and prevention.
Kenneth Rosen - I am a medical research doctor with more than 20 years of experience studying how the nervous system and skeletal muscle develop and ...
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