Single nucleotide polymorphism

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DNA molecule 1 differs from DNA molecule 2 in a single base pair.

By the term single nucleotide polymorphism ( SNP , engl. S ingle N ucleotide P olymorphism ; spoken in the laboratory jargon, snip ') is a variation of a single base pair in a complementary DNA referred -Doppelstrang. SNPs are inherited and inheritable genetic variants. The concept of mutation , which usually describes a new change that has occurred, must be distinguished from this .

properties

SNPs represent around 90% of all genetic variants in the human genome. They do not occur evenly, but rather unevenly in certain regions. Two thirds of all SNPs consist of the replacement of cytosine by thymine , since cytosine in the vertebrate genome is converted by methylation into 5-methylcytosine, which can then deaminate to thymine .

SNPs can be located in non-coding gene segments (outside of genes and in introns ) or in coding gene segments that are transcribed into proteins . In the latter case, a distinction is so-called "dumb" ( silent ) or "synonymous" SNPs, but the nucleotide sequence due to the degeneracy of the genetic code, do not alter the deduced amino acid sequence, and "non-synonymous" SNPs relevant to an amino acid exchange in the Lead codon. Even if an SNP is located in a non-coding genomic region, it can have effects on gene transcription (regulatory SNPs) if it is e.g. B. is in DNA sections to which transcription factors ( enhancers , silencers ) or RNA polymerases bind ( promoters ). By means of SNPs in an intron, e.g. B. also create a "cryptic" splice point .

SNPs are also referred to as "successful point mutations "; H. as genetic changes that have prevailed to a certain extent in the gene pool of a population, i.e. have become hereditary changes in it. Some SNPs correlate e.g. B. with certain reactions of the organism with certain infections or contact with special substances. Their scientific importance lies in their frequent occurrence and high variability, and they are also very quick and easy to determine. For this reason, they are used, for example, in the search for quantitative trait loci , i.e. chromosome segments with an influence on the expression of a quantitative trait, for the identification of individuals and for diagnoses of relationship, but also in research on drug tolerance and the like. used. The extent of common SNPs is used in genetic genealogy to determine the degree or relationship.

Methods for identifying single nucleotide polymorphisms are e.g. B. DNA sequencing , microarrays and, in connection with allele-specific oligonucleotides, the polymerase chain reaction and isothermal DNA amplification .

Examples and medical significance

In the past, little attention was paid to the SNPs, especially when they are located in non-coding gene segments. They were thought to be largely meaningless variants. As a result of large-scale complete genome analyzes, it is now known that some SNPs influence the risk of certain diseases in a complex, largely not understood way. This applies, for example, to individual non-coding SNPs in the human genes IKZF1 , ARID5B and CEBPE and the associated risk of developing acute lymphoblastic leukemia .

SNPs in the NOD2 / CARD15 gene are associated with an increased incidence of Crohn's disease , a chronic inflammatory bowel disease . Other SNPs can alter the effectiveness of a medical treatment. Certain non-coding single nucleotide polymorphisms in the IL28B gene influence the effectiveness of treatment for hepatitis C with pegylated interferon-alpha .

Alleles characterized by a single nucleotide change need not have a negative impact on the individual. Some have no recognizable consequences for the phenotype, other variants are even beneficial to the organism. Europeans owe their lactose tolerance to an SNP in the intron of the MCM6 gene , which is 5 'from LCT (lactase).

Variations in the human FOXO3 gene are responsible for noticeable longevity. Two identified single nucleotide variants were shown to be significant enhancers of human longevity, which is associated with increased synthesis of FOXO3 mRNA in various tissues .

See also

Web links

Individual evidence

  1. E Papaemmanuil, FJ Hosking, J Vijayakrishnan, A Price, B Olver, E Sheridan, SE Kinsey, T Lightfoot, E Roman, JA Irving, JM Allan, IP Tomlinson, M Taylor, M Greaves, RS Houlston: Loci on 7p12. 2, 10q21.2 and 14q11.2 are associated with the risk of childhood acute lymphoblastic leukemia . In: Nat Genet. , 2009, 41 (9), pp. 1006-1010, doi: 10.1038 / ng.430 , PMID 19684604
  2. ^ Hugot et al .: Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's Disease . In: Nature , Volume 411, May 2001, pp. 599-603, PMID 11385576 .
  3. ^ Ogura et al .: A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease . In: Nature , Volume 411, May 2001, pp. 603-606, PMID 11385577 . (free full text).
  4. DL Thomas, CL Thio, MP Martin, Y Qi, D Ge, C O'Huigin, J Kidd, K Kidd, SI Khakoo, G Alexander, JJ Goedert, GD Kirk, SM Donfield, HR Rosen, LH Tobler, MP Busch , JG McHutchison, DB Goldstein, M Carrington: Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. In: Nature , 2009, 461 (7265), pp. 798-801. doi: 10.1038 / nature08463 , PMID 19759533 .
  5. T. Bersaglieri, PC Sabeti et al. a .: Genetic signatures of strong recent positive selection at the lactase gene. In: American Journal of Human Genetics . Volume 74, number 6, June 2004, pp. 1111-1120, doi: 10.1086 / 421051 , PMID 15114531 , PMC 1182075 (free full text).
  6. Friederike Flachsbart, Janina Dose, Liljana Gentschew, Claudia Geismann, another 29 authors and Almut Nebel: Identification and characterization of two functional variants in the human longevity gene FOXO3. In: Nature Communication 8/2017: 2063, 1–12. doi : 10.1038 / s41467-017-02183-y .