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Single nucleotide polymorphism

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Also listed as: SNP
Related terms
Background
Methods
Research
Implications
Limitations
Safety
Future research
Author information
Bibliography

Related Terms
  • Adenine, chromosome, cytogenetics, cytosine, DNA, fluorescence, genome, genotype, guanine, Human Genome Project, hybridization, molecular biology, nucleotide, PCR, pharmacogenomics, phenotype, polymorphism, thymine.

Background
  • A molecule called deoxyribonucleic acid (DNA) within the nucleus of every cell of every organism contains the blueprints for that organism's growth and function. A gene is a short segment of DNA that can be assigned a function, such as designating the structure of a protein. All of the genes in an organism are collectively called the genome. Many segments of DNA do not code for proteins. Some turn genes on and some turn genes off, but most of them are poorly understood at this time.
  • DNA is a very long and complex chemical represented by a code of four "letters," which are small chemicals called nucleotides. These nucleotides include adenine (A), thymine (T), guanine (G), and cytosine (C). Consequently, a code may read: "AATGCGCCTTTGAGGTC," and so on. Three letters in sequence designate an amino acid. Amino acids arranged linearly form a protein. Proteins are the workers in the body; they do all the construction, make up a good portion of what is built, and perform most of the operations that sustain life activities. Some proteins make non-protein chemicals, such as cortisone and adrenaline, which the body needs to function.
  • The DNA found in all individuals in the world is 99.9% identical. The remaining 0.1% accounts for all of the differences observed between individuals. That 0.1% represents about 1.5 million opportunities to be unique. A single nucleotide polymorphism (SNP, which is pronounced "snip") is a natural variation in the population. SNPs account for at least 90% of that 0.1%.
  • By definition, a SNP must differ by a single nucleotide of the DNA code at least 1% of the time. If the variation exists less than 1% of the time, it is regarded as a mutation. This difference between SNPs and mutations is an artificial designation used to differentiate between the two on the basis of their frequency. Mutations, for all practical purposes, are never beneficial and appear randomly. SNPs, on the other hand, have survived and propagated to the point that they are present in at least one out of 100 individuals. That success has implications that require the two to be assigned different names so the reasons for the differences can be discussed and explored. For example, some but not all of these variations affect the phenotype of the organism. "Phenotype" refers to structure or function, such as blue eyes, curly hair, or the ability to synthesize vitamin C.

Methods
  • A single nucleotide polymorphism (SNP) is a natural variation in the human genome, one that is not exactly the same as everyone else's. By definition, it must differ by a single nucleotide of the DNA code at least 1% of the time. These nucleotides include adenine (A), thymine (T), guanine (G), and cytosine (C).
  • The recognition of SNPs and a great many other features of our genome are the results of the Human Genome Project and the larger arena of molecular biology and cytogenetics. The Human Genome Project was an expensive, exhaustive work that occupied many years. The result was the identification of the complete chemical structure of human DNA one nucleotide at a time--all three billion of them. The technology used for human genes has also been used for many other kinds of creatures, including plants, animals, and bacteria. These discoveries have characterized in fine detail the chemistry of life and opened a new era in medical and biological research. There is now a vast library of genes from many different creatures that scientists can access.
  • SNPs are identified by the conceptually simple process of comparing DNA sequences from one individual to another. For instance, the G to C conversion in the following two sequences would qualify as a SNP if it was found in at least 1% of the population: "AATGCGCCTTTGAGGTC" to "AATGCGCCTTTCAGGTC." To find such a change requires searching through many individual genomes. In order to qualify such a change as a SNP it is necessary to compare a great number of individual sequences to prove that it occurs in at least 1% of them. The process used to sequence a DNA strand requires isolating one nucleotide at a time from the end of the strand and identifying it individually. Today this process is highly automated using machines called sequencers.

Research
  • Cancer treatment: Cancer is the most active current area of research in single nucleotide polymorphisms (SNPs). Each individual cancer has its own unique set of abnormalities that allow it to grow and spread. Cancer drugs can be made more effective when the exact genetic nature of an individual and his or her cancer are completely identified. Present efforts are directed only at building a database of SNPs. Next, the focus will shift to gathering a vast amount of accumulated data. These data can be refined and distilled until targets appear that are necessary for the survival of a particular cancer.
  • One such target is the sequence of events that allows blood vessels to grow into a cancerous tumor. Without these blood vessels, the cancer would starve from lack of oxygen and nutrients. A potential means of treating the cancer involves isolating a vulnerable molecule required for that sequence of events and creating a way to inactivate that molecule. After that point, the process entails testing the treatment in cell cultures, then laboratory animals, then healthy human volunteers, and then cancer patients to see if it is effective and safe.
  • Disease susceptibility: Each person will be afflicted by some disease at some point in his or her life. Although much of what determines whether an individual has a disease depends on environmental factors such as nutrition and exposure to infectious agents and environmental toxins, genetic individuality plays a large and often defining role in susceptibility to illness. Classic examples of SNPs causing disease are cystic fibrosis and sickle cell trait. At present there is no way to modify an individual's genetic makeup to improve his or her health. Only indirect means such as consuming a healthful diet and getting regular exercise are now available.
  • Drug response: Likewise, individual response to drugs depends to a great extent on SNPs. The science of matching specific genetic profiles to drugs is called pharmacogenomics. Physicians today can make only educated guesses as to which medicines will work on which patients, and they often have no way of knowing which patients will have an adverse drug reaction. Genetic variations or SNPs will eventually help clinicians predict which drugs will work and which drugs will cause adverse reactions. So far there seems to be no specific link identified between any drug and a SNP, but researchers are beginning to identify variations in the way individuals process drugs that will soon lead to specific recommendations.
  • Forensics: SNPs are the key to identifying a criminal or the biological father of a child through DNA analysis. A criminal can be identified if a DNA sample taken from the criminal has the same SNPs as a DNA specimen from a crime scene. A father can be identified if he and his child have the same set of SNPs. The greater the distance between relatives, the more SNPs are needed to demonstrate family relationships.
  • Infectious diseases: Currently, research is being done on infectious agents (germs) to characterize their life processes. Based on this information, researchers aim to develop methods to interrupt them. This process is very similar to cancer research because infectious agents behave in many ways like cancers. Each has its own ways of surviving and injuring its host and each way is determined by its DNA. Identifying the unique DNA that causes these germs to do harm is a step toward reducing the damage.
  • Other diseases: Other diseases are also influenced by the genetic individualities of patients. SNPs determine to a great extent whether one individual has asthma, another heart disease, and another arthritis. At first medical science may be able to predict which diseases a person is most likely to have. That ability does not appear to be far off in the future. From there, a greater understanding of how to treat and prevent the disease will likely evolve.

Implications
  • A single nucleotide polymorphism (SNP) is a natural variation in the human genome, one that is not exactly the same as everyone else's. By definition, it must differ by a single nucleotide of the DNA code at least 1% of the time. These nucleotides include adenine (A), thymine (T), guanine (G), and cytosine (C).
  • Now that the database of individual genomes is large enough, comparisons can be made from one to the next. When a known gene is found to have a single nucleotide variation at least 1% of the time it is identified as a SNP. There are enormous libraries of SNPs now freely available to anyone wishing to access them. Some of the current avenues of research include forensics, cancer, general disease prevention, and pharmacology.
  • SNP identification and analysis techniques are well enough developed at the present time for use in criminal investigations and paternity cases. A criminal can be identified if a DNA sample taken from the criminal has the same SNPs as a DNA specimen from a crime scene. A father can be identified if he and his child have the same set of SNPs. The greater the distance between relatives, the more SNPs are needed to demonstrate family relationships.

Limitations
  • A single nucleotide polymorphism (SNP) is a natural variation in the human genome, one that is not exactly the same as everyone else's. By definition, it must differ by a single nucleotide of the DNA code at least 1% of the time. These nucleotides include adenine (A), thymine (T), guanine (G), and cytosine (C).
  • Laboratory errors are inevitable because human error is also inevitable. Much research is devoted to minimizing these errors because each one may affect a human life. Simplifying laboratory procedures is one goal of research in this area. The easier a test is to perform and the fewer steps required, the less likely it is that an error will occur. In the case of SNPs, which are currently used only for diagnosis, a mistaken result could lead to unnecessary further testing and a great deal of patient anxiety. Simplification and standardization also lead to lower costs and greater availability of the test.

Safety




Future research
  • A single nucleotide polymorphism (SNP) is a natural variation in the human genome, one that is not exactly the same as everyone else's. By definition, it must differ by a single nucleotide of the DNA code at least 1% of the time.
  • Cancer treatment: Progress in the area of cancer will accelerate, first to identify mechanisms that promote cancers, then to characterize individual cancers, then to develop treatments that target vulnerable pathways in vital cancer functions. At present, there are no specific cancer treatments directly linked to SNP analysis.
  • Other diseases: Infections and many other diseases will yield useful SNP information that may ultimately lead to prevention and cure. The present situation is that diagnostic tests for specific infectious agents are in development but not yet available to the general public.
  • Drug response: Pharmacogenomics is already becoming a leading interest in the medical community. Both disease-causing agents and individual diseases will eventually be treated individually, using specific information unique to the individual and derived from SNPs and other molecular biology techniques.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography
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