What Is Internal Tandem Duplication?
Internal tandem duplication (ITD) is a type of mutation that occurs when a segment of DNA is duplicated within itself. The result of internal tandem duplication (ITD) is a more extended version of the original sequence, with the duplicated segment appearing immediately next to the original. It is also known as a tandem duplication or tandem repeat. Internal tandem duplication (ITD) can occur in any type of DNA, including genomic DNA, mRNA, or cDNA.
What Is the Effect of Internal Tandem Duplication?
ITD mutations can affect the function of the gene in which they occur. In some cases, ITD can lead to the production of abnormal or nonfunctional proteins, which can cause genetic disorders or other health problems. In other cases, ITD may have no effect on the function of a gene. ITD is a common type of mutation in many different types of cancer.
What Causes Internal Tandem Duplication?
Internal tandem duplication (ITD) can be caused by various mechanisms, including errors during DNA replication or repair, recombination, or transposition. ITD is often detected through DNA sequencing or other genetic testing methods.
An Example of Internal Tandem Duplication (ITD)
One example of internal tandem duplication (ITD) is a mutation in the FLT3 gene, which is involved in the development and function of blood cells. A specific type of ITD in the FLT3 gene, called FLT3-ITD, has been linked to several types of cancer, including acute myeloid leukemia (AML).
FLT3-ITD is characterized by the duplication of a specific stretch of DNA within the FLT3 gene. This duplication results in the production of an abnormal version of the FLT3 protein, which can lead to the uncontrolled growth and division of blood cells, resulting in the development of leukemia. You can read more about the FLT3 gene in my series of blog posts about this gene.
Diagnosis of FLT3-ITD is typically made through genetic testing, such as DNA sequencing, and it is often used to help guide treatment decisions for people with AML.
What Genes Most Commonly Have Internal Tandem Duplications?
Internal tandem duplications (ITD) can occur in any type of gene and can have various effects on the gene's function. Some genes that are known to have ITDs include:
FLT3: This gene is involved in the development and function of blood cells. A specific type of ITD in the FLT3 gene, called FLT3-ITD, has been linked to several types of cancer, including acute myeloid leukemia (AML).
JAK2: This gene is involved in signaling pathways that control the growth and development of cells. ITDs in the JAK2 gene have been associated with myeloproliferative neoplasms, a group of disorders that affect the production of blood cells.
KIT: This gene is involved in the development and function of certain types of cells, including skin cells and cells in the immune system. ITDs in the KIT gene have been associated with several types of cancer, including gastrointestinal stromal tumors (GIST) and some types of leukemia.
PDGFRA: This gene is involved in the development and function of blood vessels and connective tissue. ITDs in the PDGFRA gene have been associated with GIST and other types of cancer.
NRAS: This gene is involved in signaling pathways that control cell growth and division. ITDs in the NRAS gene have been associated with several types of cancer, including melanoma and leukemia.
It's important to note that the presence of an ITD in one of these genes does not necessarily mean that a person will develop a genetic disorder or cancer. The effects of an ITD can vary and may depend on other genetic and environmental factors.
How Is the ITD Ratio Calculated?
The internal tandem duplication (ITD) ratio measures the amount of ITD present in a sample of DNA. ITD ratio is typically calculated by comparing the amount of ITD present to the total DNA in the sample. There are several different methods for calculating the ITD ratio, and the specific method used can depend on the specific type of ITD and the tools and resources available. You can check out more about how the ITD ratio is calculated in this blog post.
It's important to note that the ITD ratio may vary depending on the specific sample being analyzed and the method used to calculate the ratio. ITD ratio may be used in various contexts, including research, diagnostic testing, and treatment monitoring.