Can changes in noncoding DNA affect health and development?
It is well established that changes in genes can alter a protein’s function in the body, potentially causing health problems. It is becoming clear that changes in regions of DNA that do not contain genes (noncoding DNA) can also lead to disease.
Many regions of noncoding DNA play a role in the control of gene activity, determining when and where certain genes are turned on or off. By altering these sequences, a mutation in noncoding DNA can cause a protein to be expressed in the wrong place or at the wrong time or can reduce or eliminate expression of an important protein when it is needed. Not all changes in noncoding DNA have an impact on health, but those that alter the expression pattern of a protein that plays a critical role in the body can disrupt normal development or cause a health problem.
Mutations in noncoding DNA have been linked to developmental disorders such as isolated Pierre Robin sequence, which is caused by changes in enhancer elements that control the activity of the SOX9 gene. Noncoding DNA mutations have also been associated with several types of cancer. In addition to enhancer elements, these mutations can disrupt other regulatory elements including promoters, insulators, and silencers. Mutations in regions that provide instructions for making functional RNA molecules, such as transfer RNAs, microRNAs, or long noncoding RNAs, have also been implicated in disease.
The same types of genetic changes that occur in genes or that alter the structure of chromosomescan affect health and development when they occur in noncoding DNA. These mutations include changes in single DNA building blocks (point mutations), insertions, deletions, duplications, and translocations. Noncoding DNA mutations can be inherited from a parent or acquired during a person’s life.
Much is still unknown about how to identify functional regions of noncoding DNA and the role such regions play. As a result, linking genetic changes in noncoding DNA to their effects on certain genes and to health conditions is difficult. The roles of noncoding DNA and the effects of genetic changes in it are growing areas of research.
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