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Pulmonary Hypertension Directory
Pulmonary hypertension is high blood pressure in the arteries leading from the heart to the lungs. Pulmonary hypertension is a different condition than ordinary high blood pressure (hypertension). Many different conditions can cause pulmonary hypertension, including congestive heart failure, blood clots in the lungs, HIV infection, and more. In most patients, pulmonary hypertension has an identifiable cause. Although there's no cure, treatments can reduce the symptoms of primary pulmonary hypertension, including shortness of breath. Follow the links below to find WebMD's comprehensive coverage about pulmonary hypertension, what it looks like, how to treat it, and much more.
Medical Reference View AllFeatures News Archive View AllExtracellular Control Of TGFβ Signalling In Vascular Development And Disease
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Genetic Mutation
So, how do mutations occur? The answer to this question is closely linked to the molecular details of how both DNA and the entire genome are organized. The smallest mutations are point mutations, in which only a single base pair is changed into another base pair. Yet another type of mutation is the nonsynonymous mutation, in which an amino acid sequence is changed. Such mutations lead to either the production of a different protein or the premature termination of a protein.
As opposed to nonsynonymous mutations, synonymous mutations do not change an amino acid sequence, although they occur, by definition, only in sequences that code for amino acids. Synonymous mutations exist because many amino acids are encoded by multiple codons. Base pairs can also have diverse regulating properties if they are located in introns, intergenic regions, or even within the coding sequence of genes. For some historic reasons, all of these groups are often subsumed with synonymous mutations under the label "silent" mutations. Depending on their function, such silent mutations can be anything from truly silent to extraordinarily important, the latter implying that working sequences are kept constant by purifying selection. This is the most likely explanation for the existence of ultraconserved noncoding elements that have survived for more than 100 million years without substantial change, as found by comparing the genomes of several vertebrates (Sandelin et al., 2004).
Mutations may also take the form of insertions or deletions, which are together known as indels. Indels can have a wide variety of lengths. At the short end of the spectrum, indels of one or two base pairs within coding sequences have the greatest effect, because they will inevitably cause a frameshift (only the addition of one or more three-base-pair codons will keep a protein approximately intact). At the intermediate level, indels can affect parts of a gene or whole groups of genes. At the largest level, whole chromosomes or even whole copies of the genome can be affected by insertions or deletions, although such mutations are usually no longer subsumed under the label indel. At this high level, it is also possible to invert or translocate entire sections of a chromosome, and chromosomes can even fuse or break apart. If a large number of genes are lost as a result of one of these processes, then the consequences are usually very harmful. Of course, different genetic systems react differently to such events.
Finally, still other sources of mutations are the many different types of transposable elements, which are small entities of DNA that possess a mechanism that permits them to move around within the genome. Some of these elements copy and paste themselves into new locations, while others use a cut-and-paste method. Such movements can disrupt existing gene functions (by insertion in the middle of another gene), activate dormant gene functions (by perfect excision from a gene that was switched off by an earlier insertion), or occasionally lead to the production of new genes (by pasting material from different genes together).
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