WordNet
- (genetics) any event that changes genetic structure; any alteration in the inherited nucleic acid sequence of the genotype of an organism (同)genetic mutation, chromosomal_mutation
- a change or alteration in form or qualities
PrepTutorEJDIC
- 変化,俸転 / (生物の)突然変異;その変種
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/01 21:47:28」(JST)
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"Missense" redirects here.
This image shows an example of missense mutation. One of the nucleotides (adenine) is replaced by another nucleotide (cytosine) in the DNA sequence. This results in an incorrect amino acid (proline) being incorporated into the protein sequence.
In genetics, a missense mutation (a type of nonsynonymous substitution) is a point mutation in which a single nucleotide change results in a codon that codes for a different amino acid.[1] Another type of nonsynonymous substitution is a nonsense mutation in which a codon is changed to a premature stop codon that results in truncation of the resulting protein. Missense mutations can render the resulting protein nonfunctional,[2] and such mutations are responsible for diseases such as Epidermolysis bullosa, sickle-cell disease, and SOD1 mediated ALS. [3]
In the most common variant of sickle-cell disease, the 20th nucleotide of the gene for the beta chain of hemoglobin is altered from the codon GAG to GTG. Thus, the 6th amino acid glutamic acid is substituted by valine — notated as an "E6V" mutation — and the protein is sufficiently altered to cause the sickle-cell disease.[4]
Not all missense mutations lead to appreciable protein changes. An amino acid may be replaced by an amino acid of very similar chemical properties, in which case, the protein may still function normally; this is termed a neutral, "quiet", "silent" or conservative mutation. Alternatively, the amino acid substitution could occur in a region of the protein which does not significantly affect the protein secondary structure or function. When an amino acid may be encoded by more than one codon (so-called "degenerate coding") a mutation in a codon may not produce any change in translation; this would be a silent mutation (a type of synonymous substitution, which is not always silent) and not a missense mutation.
Contents
- 1 Example
- 2 Experimental analysis
- 3 See also
- 4 References
- 5 External links
Example
Wild type (left) and mutated (right) form of lamin A (pdb id: 1IFR). Normally, Arginine 527 (blue) forms salt bridge with glutamate 527 (magenta), but R527L substitution results in breaking this interaction (leucine has a nonpolar tail and therefore cannot form a static salt bridge).
DNA: 5' - AAC AGC CTG CGT ACG GCT CTC - 3'
3' - TTG TCG GAC GCA TGC CGA GAG - 5'
mRNA: 5' - AAC AGC CUG CGU GCG ACG CUC - 3'
Protein: Asn Ser Leu Arg Thr Ala Leu
LMNA missense mutation (c.1580G>T) introduced at LMNA gene - position 1580 (nt) in the DNA sequence (CGT) causing the guanine to be replaced with the thymine, yielding CTT in the DNA sequence. This results at the protein level in the replacement of the arginine by the leucine at the position 527.[5] This leads to destruction of salt bridge and structure destabilization. At phenotype level this manifest with overlapping mandibuloacral dysplasia and progeria syndrome.
The resulting transcript and protein product is:
DNA: 5' - AAC AGC CTG CTT ACG GCT CTC - 3'
3' - TTG TCG GAC GAA TGC CGA GAG - 5'
mRNA: 5' - AAC AGC CUG CUU GCG ACG CUC - 3'
Protein: Asn Ser Leu Leu Thr Ala Leu
Experimental analysis
Cancer associated missense mutations can lead to drastic destabilisation of the resulting protein.[6] A novel method to screen for such changes was proposed recently, namely Fast parallel proteolysis (FASTpp).[7]
See also
References
- ^ "Definition of Missense mutation". MedTerms medical dictionary. MedicineNet. 2012-03-19.
- ^ Minde, David P; Anvarian, Zeinab; Rüdiger, Stefan GD; Maurice, Madelon M (1 January 2011). "Messing up disorder: how do missense mutations in the tumor suppressor protein APC lead to cancer?". Molecular Cancer 10 (1): 101. doi:10.1186/1476-4598-10-101. PMC 3170638. PMID 21859464.
- ^ Boillée, S; Vande Velde, C; Cleveland, D. W. (2006). "ALS: A disease of motor neurons and their nonneuronal neighbors". Neuron 52 (1): 39–59. doi:10.1016/j.neuron.2006.09.018. PMID 17015226.
- ^ "141900 Hemoglobin—Beta Locus; HBB: .0243 Hemoglobin S. Sickle Cell Anemia, included. Malaria, Resistance to, included. HBB, GLU6VAL — 141900.0243". Online 'Mendelian Inheritance in Man' (OMIM).
- ^ Al-Haggar M, Madej-Pilarczyk A, Kozlowski L, Bujnicki JM, Yahia S, Abdel-Hadi D, Shams A, Ahmad N, Hamed S, Puzianowska-Kuznicka M (2012). "A novel homozygous p.Arg527Leu LMNA mutation in two unrelated Egyptian families causes overlapping mandibuloacral dysplasia and progeria syndrome.". Eur J Hum Genet. 20 (11): 1134–40. doi:10.1038/ejhg.2012.77. PMC 3476705. PMID 22549407.
- ^ Bullock, AN; Henckel, J; DeDecker, BS; Johnson, CM; Nikolova, PV; Proctor, MR; Lane, DP; Fersht, AR (23 December 1997). "Thermodynamic stability of wild-type and mutant p53 core domain". Proc. Natl. Acad. Sci. U.S.A. 94 (26): 14338–42. doi:10.1073/pnas.94.26.14338. PMC 24967. PMID 9405613.
- ^ Minde, DP; Maurice, MM; Rüdiger, SG (2012). "Determining biophysical protein stability in lysates by a fast proteolysis assay, FASTpp". PLoS ONE 7 (10): e46147. doi:10.1371/journal.pone.0046147. PMC 3463568. PMID 23056252.
External links
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Wikimedia Commons has media related to Missense mutation. |
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Mutation
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| Mechanisms of mutation |
- Insertion
- Deletion
- Substitution
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| Mutation with respect to structure |
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Point mutation
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- Nonsense mutation
- Missense mutation
- Silent mutation
- Frameshift mutation
- Dynamic mutation
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Large-scale mutation
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- Chromosomal translocations
- Chromosomal inversions
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| Mutation with respect to overall fitness |
- Deleterious mutation
- Advantageous mutation
- Neutral mutation
- Nearly neutral mutation
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UpToDate Contents
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English Journal
- Incidence of BRCA1 somatic mutations and response to neoadjuvant chemotherapy in Chinese women with triple-negative breast cancer.
- Li M1, Zhang J1, Ouyang T1, Li J1, Wang T1, Fan Z1, Fan T1, Lin B1, Xie Y2.
- Gene.Gene.2016 Jun 10;584(1):26-30. doi: 10.1016/j.gene.2016.03.004. Epub 2016 Mar 5.
- BACKGROUND: The prevalence of BRCA1 somatic mutations status in triple-negative breast cancer (TNBC) has not been well documented. The aims of this study were to determine the frequency of BRCA1 somatic mutations and to investigate the association between BRCA1 deleterious somatic mutation status an
- PMID 26956035
- Molecular Dynamics Studies on D835N Mutation in FLT3-Its Impact on FLT3 Protein Structure.
- Swetha RG1, Ramaiah S1, Anbarasu A1.
- Journal of cellular biochemistry.J Cell Biochem.2016 Jun;117(6):1439-45. doi: 10.1002/jcb.25434. Epub 2015 Nov 30.
- Mutations in Fetal Liver Tyrosine Kinase 3 (FLT3) genes are implicated in the constitutive activation and development of Acute Myeloid Leukaemia (AML). They are involved in signalling pathway of autonomous proliferation and block differentiation in leukaemia cells. FLT3 is considered as a promising
- PMID 26566084
- A Mitochondrial DNA A8701G Mutation Associated with Maternally Inherited Hypertension and Dilated Cardiomyopathy in a Chinese Pedigree of a Consanguineous Marriage.
- Zhu Y, Gu X1, Xu C.
- Chinese medical journal.Chin Med J (Engl).2016 5th Feb;129(3):259-266. doi: 10.4103/0366-6999.174491.
- BACKGROUND: Cardiovascular diseases, including dilated cardiomyopathy (DCM) and hypertension, are the leading cause of death worldwide. The role of mitochondrial DNA (mtDNA) in the pathogenesis of these diseases has not been completely clarified. In this study, we evaluate whether A8701G mutation is
- PMID 26831225
Japanese Journal
- Aicardi-Goutières Syndrome Is Caused by IFIH1 Mutations.
- Oda Hirotsugu,Nakagawa Kenji,Abe Junya,Awaya Tomonari,Funabiki Masahide,Hijikata Atsushi,Nishikomori Ryuta,Funatsuka Makoto,Ohshima Yusei,Sugawara Yuji,Yasumi Takahiro,Kato Hiroki,Shirai Tsuyoshi,Ohara Osamu,Fujita Takashi,Heike Toshio
- American journal of human genetics 95(1), 121-125, 2014-07-03
- … After removal of the common polymorphisms found in SNP databases, we were able to identify IFIH1 heterozygous missense mutations in all three. … IFIH1 encodes MDA5, and mutant MDA5 lacked ligand-specific responsiveness, similarly to the dominant Ifih1 mutation responsible for the SLE mouse model that results in type I interferon overproduction. …
- NAID 120005460706
- A case of isolated hypocalciuric hypercalcemia and type 2 diabetes mellitus followed by Grave's disease
- Tojikubo Masayuki,Akazawa Shoichi,Nakano Yuko,Nakamura Satoe,Yamashita Shunichi
- Acta medica Nagasakiensia 59(1), 27-31, 2014-07
- … However, the patient did have a missense mutation of codon 990 (R990G) in the intracellular domain, which has been reported to be a site of polymorphism, as well as a mutation of intron 6 (16 base pairs downstream from the exon-intron boundary: IVS6+16). …
- NAID 120005468239
Related Links
- A missense mutation may lead to the synthesis of a protein that is nonfunctional. For instance in sicke-cell disease, the 20th nucleotide of the gene for the beta chain of hemoglobin on chromosome 11 is changed from the codon ...
- A missense mutation is when the change of a single base pair causes the substitution of a different amino acid in the resulting protein. This amino acid substitution may have no effect, or it may render the protein nonfunctional. ...
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