関: nonsense codon、nonsense mutation、premature termination codon、PTC

WordNet

cause to stop; "stop a car"; "stop the thief"
a brief stay in the course of a journey; "they made a stopover to visit their friends" (同)stopover, layover
the act of stopping something; "the third baseman made some remarkable stops"; "his stoppage of the flow resulted in a flood" (同)stoppage
(music) a knob on an organ that is pulled to change the sound quality from the organ pipes; "the organist pulled out all the stops"
the event of something ending; "it came to a stop at the bottom of the hill" (同)halt
a spot where something halts or pauses; "his next stop is Atlanta"
come to a halt, stop moving; "the car stopped"; "She stopped in front of a store window" (同)halt
stop from happening or developing; "Block his election"; "Halt the process" (同)halt, block, kibosh
interrupt a trip; "we stopped at Aunt Marys house"; "they stopped for three days in Florence" (同)stop over
born after a gestation period of less than the normal time; "a premature infant"
uncommonly early or before the expected time; "illness led to his premature death"; "alcohol brought him to an untimely end" (同)untimely
major food fish of Arctic and cold-temperate waters (同)codfish
lean white flesh of important North Atlantic food fish; usually baked or poached (同)codfish
a specific sequence of three adjacent nucleotides on a strand of DNA or RNA that specifies the genetic code information for synthesizing a particular amino acid

PrepTutorEJDIC

〈動いているもの〉‘を'『止める』 / 〈供給など〉‘を'停止する / …‘を'阻止する,やめさせる / 〈自分がしていること〉‘を'『やめる』,中断する / 〈穴・口など〉‘を'ふさぐ,〈びんなど〉‘に'せんをする / 〈相手の一撃など〉‘を'かわす;〈相手〉‘を'打ち負かす,ノックアウトする / 〈楽器の弦・穴〉‘を'指で押さえる,〈音〉‘を'指で押さえて出す / 〈動いているものが〉『止まる』,停止する,立ち止まる / 〈仕事・話などが〉『中断する』;〈雨などが〉やむ / 〈人が〉仕事(話など)をやめる,手を休める,一息つく / 《話》(…に)滞在する,とどまる《+『at』+『名』〈場所〉『,』+『with』+『名』〈人〉》 / 『止まること』,停止,中止,中断 / (旅先での)短期間の滞在,立ち寄り / (道路の)停留所 / (穴などを)ふさぐこと…(びんなどの)せん / (パイプオルガンなどの)ストップ,音栓(肝先) / 句読点,(特に)終止符 / (レンズの)絞り / 閉鎖音([p][b][k]など)
時期尚早の,早すぎた / 早計の,早まった / 早産の
=codfish 1
〈人〉'を'ばかにする

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/10/19 11:48:15」(JST)

wiki en

In genetics, a nonsense mutation is a point mutation in a sequence of DNA that results in a premature stop codon, or a nonsense codon in the transcribed mRNA, and in a truncated, incomplete, and usually nonfunctional protein product. It differs from a missense mutation, which is a point mutation where a single nucleotide is changed to cause substitution of a different amino acid. Some genetic disorders, such as thalassemia and DMD, result from nonsense mutations.

Simple example[edit]

    DNA: 5' - ATG ACT CAC CGA GCG CGA AGC TGA - 3'
         3' - TAC TGA GTG GCT CGC GCT TCG ACT - 5'
   mRNA: 5' - AUG ACU CAC CGA GCG CGA AGC UGA - 3'
Protein:      Met Thr His Arg Ala Arg Ser Stop

Suppose that a nonsense mutation was introduced at the fourth triplet in the DNA sequence (CGA) causing the cytosine to be replaced with thymine, yielding TGA in the DNA sequence. Since TGA is transcribed-then-translated as UGA, the resulting transcript and protein product would be:

    DNA: 5' - ATG ACT CAC TGA GCG CGA AGC TGA - 3'
         3' - TAC TGA GTG ACT CGC GCT TCG ACT - 5'
   mRNA: 5' - AUG ACU CAC UGA GCG CGU AGC UGA - 3'
Protein:      Met Thr His Stop

The remaining codons of the mRNA are not translated into amino proteins because the stop codon is prematurely reached during translation. This can yield a truncated abbreviated protein product, which quite often lacks the functionality of the normal, non-mutant protein.

Nonsense-mediated mRNA decay[edit]

Despite an expected tendency for premature termination codons to yield shortened polypeptide products, in fact the formation of truncated proteins does not occur often in vivo. Many organisms—including humans and lower species, such as yeast—employ a nonsense-mediated mRNA decay pathway, which degrades mRNAs containing nonsense mutations before they are translated into nonfunctional polypeptides.

The three stop codons have been given names: UAG is amber, UGA is opal (sometimes also called umber), and UAA is ochre. “Amber” was named by discoverers Richard Epstein and Charles Steinberg after their friend Harris Bernstein, whose last name means “amber” in german.^[1] The other two stop codons were named “ochre” and “opal” in order to keep the “color names” theme. Stop codons are also called “termination”or “nonsense” codons. They signal release of the nascent polypeptide from the ribosome because there is no cognate tRNA that has anticodons complementary to these stop signals, and so a release factor binds to the ribosome instead.

Pathology associated with nonsense mutations[edit]

Selection of notable mutations, ordered in a standard table of the genetic code of amino acids.^[2] Nonsense mutations are marked by red arrows.

Nonsense mutations can cause a genetic disease by damaging a gene responsible for a specific protein, for example, dystrophin in Duchenne muscular dystrophy. The same disease may, however, be caused by other kinds of damage to the same gene. Examples of diseases in which nonsense mutations are known to be among the causes include:

Cystic fibrosis (caused by the G542X mutation in the cystic fibrosis transmembrane conductance regulator gene).

Duchenne muscular dystrophy (dystrophin)

Beta thalassaemia (β-globin)

Hurler syndrome

An experimental drug known as PTC124 may be useful in treating some cases of each of the above diseases (that is, the cases caused by a nonsense mutation). PTC124 was scheduled to enter the final phase of clinical trials in 2007.^[3]

External links and references[edit]

^ Edgar B (October 2004). "The genome of bacteriophage T4: an archeological dig". Genetics 168 (2): 575–82. PMC 1448817. PMID 15514035.
^ References for the image are found in Wikimedia Commons page at: Commons:File:Notable mutations.svg#References.
^ Henderson, Mark (23 April 2007). "Daily pill to beat genetic diseases". The Times (London). Retrieved 2007-10-23.

Mutations
Nonsense mutation (Medical dictionary)
Gatfield D, Unterholzner L, Ciccarelli FD, Bork P, Izaurralde E (1 August 2003). "Nonsense-mediated mRNA decay in Drosophila: at the intersection of the yeast and mammalian pathways". The EMBO Journal 22 (15): 3960–70. PMID 12881430.
Welch EM, et al. (3 May 2007). "PTC124 targets genetic disorders caused by nonsense mutations". Nature 447 (7140): 87–91. doi:10.1038/nature05756. PMID 17450125.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 遺伝性疾患の基本原則 basic principles of genetic disease
2. サラセミア症候群の分子病理 molecular pathology of the thalassemic syndromes
3. 遺伝学用語集 glossary of genetic terms
4. 原発性免疫不全症に対する遺伝子治療 gene therapy for primary immunodeficiency
5. プリオンの生物学および遺伝学 biology and genetics of prions

English Journal

Type 1 papillary renal cell carcinoma in a patient with schwannomatosis: Mosaic versus loss of SMARCB1 expression in respectively schwannoma and renal tumor cells.

Hulsebos TJ1, Kenter S1, Baas F1, Nannenberg EA2, Bleeker FE2, van Minkelen R3, van den Ouweland AM3, Wesseling P4,5, Flucke U4.
Genes, chromosomes & cancer.Genes Chromosomes Cancer.2016 Apr;55(4):350-4. doi: 10.1002/gcc.22338. Epub 2016 Jan 22.
In schwannomatosis, germline SMARCB1 or LZTR1 mutations predispose to the development of multiple benign schwannomas. Besides these, other tumors may occur in schwannomatosis patients. We present a 45-year-old male patient who developed multiple schwannomas and in addition a malignant type 1 papilla
PMID 26799435

The Effect of Heterozygosity for the ACTN3 Null Allele on Human Muscle Performance.

Garton FC1, North KN.
Medicine and science in sports and exercise.Med Sci Sports Exerc.2016 Mar;48(3):509-20. doi: 10.1249/MSS.0000000000000784.
α-Actinin-3 is primarily expressed in fast (Type II) fibers in the human skeletal muscle. Over 70% of the global population has at least one copy of a loss of function allele because of a premature stop codon in the ACTN3 gene (R577X). Homozygosity for this variant (577XX) occurs in approximately 1
PMID 26429734

Targeting Nonsense Mutations in Diseases with Translational Read-Through-Inducing Drugs (TRIDs).

Nagel-Wolfrum K1,2, Möller F3, Penner I3, Baasov T4, Wolfrum U5,6.
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy.BioDrugs.2016 Feb 17. [Epub ahead of print]
In recent years, remarkable advances in the ability to diagnose genetic disorders have been made. The identification of disease-causing genes allows the development of gene-specific therapies with the ultimate goal to develop personalized medicines for each patient according to their own specific ge
PMID 26886021