WordNet

use a shift key on a keyboard; "She could not shift so all her letters are written in lower case"
the time period during which you are at work (同)work shift, duty period
the act of moving from one place to another; "his constant shifting disrupted the class" (同)shifting
an event in which something is displaced without rotation (同)displacement
a crew of workers who work for a specific period of time
change place or direction; "Shift ones position" (同)dislodge, reposition
change gears; "you have to shift when you go down a steep hill"
change in quality; "His tone shifted"
change phonetically as part of a systematic historical change; "Grimm showed how the consonants shifted"
move and exchange for another; "shift the date for our class reunion"
move from one setting or context to another; "shift the emphasis"; "shift ones attention"
enclose in a frame, as of a picture
a framework that supports and protects a picture or a mirror; "the frame enhances but is not itself the subject of attention"; "the frame was much more valuable than the miror it held" (同)framing
a single one of a series of still transparent pictures forming a cinema, television or video film
one of the ten divisions into which bowling is divided
the framework for a pair of eyeglasses
a single drawing in a comic_strip
an application that divides the users display into two or more windows that can be scrolled independently
make up plans or basic details for; "frame a policy" (同)compose, draw_up
enclose in or as if in a frame; "frame a picture" (同)frame in, border
construct by fitting or uniting parts together (同)frame up
formulate in a particular style or language; "I wouldnt put it that way"; "She cast her request in very polite language" (同)redact, cast, put, couch
(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
continuously varying; "taffeta with shifting colors"
changing position or direction; "he drifted into the shifting crowd"; "their nervous shifting glances"; "shifty winds" (同)shifty
(of soil) unstable; "shifting sands"; "unfirm earth" (同)unfirm
provided with a frame; "there were framed snapshots of family and friends on her desk"

PrepTutorEJDIC

〈人・場所・位置など〉‘を'『移し替える』,置き換える / …‘を'変える,取り替える / 〈自動車のギヤ〉‘を'入れ変える / (…へ)『変わる』,移る《+『to』+『名』》 / 車のギヤを変える;〈車が〉ギヤが入れ変わる・『変換』,転換;移動 / (仕事、作業の)『交替』,交替製;交替の組(人);交替時間 / (特に,自動車)変速装置 / やりくり[算段],一時しのぎの手段,便法;ずるい手段,策略 / シフトドレス(肩から腰までまっすぐした線のゆったりしたワンピース);スリップ
〈C〉(建造物・機械などの)『骨組み』《+『of』+『名』》 / 〈C〉(戸・窓などの)『枠』;額縁《+『of』+『名』》《複数形で》めがねの枠 / 〈C〉『体格』 / 〈C〉(…の)構造,体制《+『of』+『名』》 / 〈C〉(簡略な)温室,温床 / 〈C〉(ボーリングで)フレーム(10回で1ゲームを構成するその各回);各回の得点を記入する枠 / 〈C〉(映画のフイルムの)一こま / 《修飾語を伴って》《a~》気持ち,気分 / (組み合わせて)…‘を'『形作る』,組み立てる;(ある目的などに合うように)〈人・物〉‘を'作り上げる / 〈考え・構想など〉‘を'心に抱く / 〈絵など〉‘を'粋に入れる,縁どる / 〈言葉など〉‘を'言う / 《話》〈人〉‘に'ぬれぎぬを着せる
変化,俸転 / (生物の)突然変異;その変種

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/05/18 22:25:01」(JST)

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[Wiki en表示]

A frameshift mutation (also called a framing error or a reading frame shift) is a genetic mutation caused by indels (insertions or deletions) of a number of nucleotides that is not evenly divisible by three from a DNA sequence. Due to the triplet nature of gene expression by codons, the insertion or deletion can change the reading frame (the grouping of the codons), resulting in a completely different translation from the original. The earlier in the sequence the deletion or insertion occurs, the more altered the protein produced is.

A frameshift mutation will in general cause the reading of the codons after the mutation to code for different amino acids. The frameshift mutation will also alter the first stop codon ("UAA", "UGA" or "UAG") encountered in the sequence. The polypeptide being created could be abnormally short or abnormally long, and will most likely not be functional.

Frameshift mutations frequently result in severe genetic diseases such as Tay-Sachs disease. A frameshift mutation is responsible for the disabling of the CCR5 HIV receptor and some types of familial hypercholesterolemia (Lewis, 2005, p. 227-228). Frameshift mutations have also been proposed as a source of biological novelty, as with the alleged creation of nylonase. However, a study by Negoro et al (2006) ^[1] found that a frameshift mutation was unlikely to have been the cause and that rather a two amino acid substitution in the catalytic cleft of an ancestral esterase amplified Ald-hydrolytic activity.

Frameshifting may also occur during protein translation, producing different proteins from overlapping open reading frames, such as the gag-pol-env retroviral proteins. This is fairly common in viruses and also occurs in bacteria and yeast (Farabaugh, 1996).

A frameshift mutation is not the same as a single-nucleotide polymorphism in which a nucleotide is replaced, rather than inserted or deleted.

Thermodynamics

The effects of neighboring bases and secondary structure on the frequency of frameshift mutations has been investigated in depth. Fluorescently tagged DNA, by means of base analogues, permits one to study the local changes of a DNA sequence. ^[2] Studies on the effects of the length of the primer strand reveal that an equilibrium mixture of four hybridization conformations was observed when template bases looped-out as a bulge, i.e. a structure flanked on both sides by duplex DNA. In contrast, a single-loop structure with an unusual unstacked DNA conformation at its downstream edge was observed when the extruded bases were positioned at the primer–template junction, showing that misalignments can be modified by neighboring DNA secondary structure.^[3]

References

^ http://www.jbc.org/content/280/47/39644.full.pdf+html
^ Johnson, Neil P.; Walter A. Baase, Peter H. von Hippel, Low-energy circular dichroism of 2-aminopurine dinucleotide as a probe of local conformation of DNA and RNA, doi:10.1073/pnas.0400591101, "PNAS 2004 101:3426-3431; published online before print March 1, 2004"
^ Baase, Walter A.; Davis Jose , Benjamin C. Ponedel , Peter H. von Hippel , and Neil P. Johnson, "DNA models of trinucleotide frameshift deletions: the formation of loops and bulges at the primer–template junction", Nucleic Acids Research 37 (5): 1682–1689, doi:10.1093/nar/gkn1042, "Nucleic Acids Research Advance Access published on April 1, 2009"

External links

MeSH Frameshift+Mutation
NCBI dbSNP database — "a central repository for both single base nucleotide substitutions and short deletion and insertion polymorphisms"
Wise2 - aligns a protein against a DNA sequence allowing frameshifts and introns
FastY - compare a DNA sequence to a protein sequence database, allowing gaps and frameshifts
Path - tool that compares two frameshift proteins (back-translation principle)

UpToDate Contents

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1. 原発性免疫不全症に対する遺伝子治療 gene therapy for primary immunodeficiency
2. 遺伝学用語集 glossary of genetic terms
3. 遺伝性疾患の基本原則 basic principles of genetic disease
4. 家族性筋萎縮性側索硬化症 familial amyotrophic lateral sclerosis
5. 進行非小細胞肺癌に対する遺伝子型による個別治療 personalized genotype directed therapy for advanced non small cell lung cancer

English Journal

Novel homozygous mutations in the WNT10B gene underlying autosomal recessive split hand/foot malformation in three consanguineous families.

Aziz A1, Irfanullah1, Khan S1, Zimri FK2, Muhammad N3, Rashid S4, Ahmad W5.Author information 1Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan.2National Institute of Rehabilitation Medicine (NIRM), Islamabad, Pakistan.3Department of Biotechnology & Genetic Engineering, Kohat University of Science & Technology (KUST), Kohat, KPK, Pakistan.4National Center for Bioinformatics, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan.5Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University Islamabad, Pakistan. Electronic address: wahmad@qau.edu.pk.AbstractSplit-hand/split-foot malformation (SHFM), representing variable degree of median clefts of hands and feet, is a genetically heterogeneous group of limb malformations with seven loci mapped on different human chromosomes. However, only 3 genes (TP63, WNT10B, DLX5) for the seven loci have been identified. The study, presented here, described three consanguineous Pakistani families segregating SHFM in autosomal recessive manner. Linkage in the families was searched by genotyping microsatellite markers and mutation screening of candidate gene was performed by Sanger DNA sequencing. Clinical features of affected members of these families exhibited SHFM phenotype with involvement of hands and feet. Genotyping using microsatellite markers mapped the families to WNT10B gene at SHFM6 on chromosome 12q13.11-q13. Subsequently, sequence analysis of WNT10B gene revealed a novel 4-bp deletion mutation (c.1165_1168delAAGT) in one family and 7-bp duplication (c.300_306dupAGGGCGG) in two other families. Structure-based analysis showed a significant conformational shift in the active binding site of mutated WNT10B (p.Lys388Glufs*36), influencing binding with Fzd8. The mutations identified in the WNT10B gene extend the body of evidence implicating it in the pathogenesis of SHFM.
Gene.Gene.2014 Jan 25;534(2):265-71. doi: 10.1016/j.gene.2013.10.047. Epub 2013 Nov 5.
Split-hand/split-foot malformation (SHFM), representing variable degree of median clefts of hands and feet, is a genetically heterogeneous group of limb malformations with seven loci mapped on different human chromosomes. However, only 3 genes (TP63, WNT10B, DLX5) for the seven loci have been identi
PMID 24211389

A novel heterozygous SOX2 mutation causing congenital bilateral anophthalmia, hypogonadotropic hypogonadism and growth hormone deficiency.

Macchiaroli A1, Kelberman D2, Auriemma RS3, Drury S4, Islam L2, Giangiobbe S1, Ironi G1, Lench N4, Sowden JC2, Colao A3, Pivonello R3, Cavallo L5, Gasperi M6, Faienza MF7.Author information 1Paediatric Endocrinology Unit, "Cardarelli" Hospital, Campobasso, Italy.2Ulverscroft Vision Research Group, Developmental Biology Unit, UCL Institute of Child Health, London, UK.3Department of Molecular and Clinical Endocrinology and Oncology, Federico II University, Napoli, Italy.4NE Thames Regional Genetics Service, Great Ormond Street Hospital for Children, London, UK.5Department of Biomedical Sciences and Human Oncology, Section of Pediatrics, University "Aldo Moro", Bari, Italy.6Department of Medicine and Health Sciences, Section of Endocrinology, University of Molise, Campobasso, Italy.7Department of Biomedical Sciences and Human Oncology, Section of Pediatrics, University "Aldo Moro", Bari, Italy. Electronic address: mariafelicia.faienza@uniba.it.AbstractHeterozygous de novo mutations in SOX2 have been reported in approximately 10-20% of patients with unilateral or bilateral anophthalmia or microphthalmia. An additional phenotype of hypopituitarism, with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, has been reported in patients carrying SOX2 alterations. We report a novel heterozygous mutation in the SOX2 gene in a male affected with congenital bilateral anophthalmia, hypogonadotrophic hypogonadism and growth hormone deficiency. The mutation we describe is a cytosine deletion in position 905 (c905delC) which causes frameshift and an aberrant C-terminal domain. Our report highlights the fact that subjects affected with eye anomalies and harboring SOX2 mutations are at high risk for gonadotropin deficiency, which has important implications for their clinical management.
Gene.Gene.2014 Jan 25;534(2):282-5. doi: 10.1016/j.gene.2013.10.043. Epub 2013 Nov 6.
Heterozygous de novo mutations in SOX2 have been reported in approximately 10-20% of patients with unilateral or bilateral anophthalmia or microphthalmia. An additional phenotype of hypopituitarism, with anterior pituitary hypoplasia and hypogonadotropic hypogonadism, has been reported in patients c
PMID 24211324

Exome sequencing identifies a novel EP300 frame shift mutation in a patient with features that overlap cornelia de lange syndrome.

Woods SA, Robinson HB, Kohler LJ, Agamanolis D, Sterbenz G, Khalifa M.Author information Department of Genetics, Akron Children's Hospital, Akron, Ohio.AbstractRubinstein-Taybi syndrome (RTS) and Cornelia de Lange syndrome (CdLS) are genetically heterogeneous multiple anomalies syndromes, each having a distinctive facial gestalt. Two genes (CREBBP and EP300) are known to cause RTS, and five (NIPBL, SMC1A, SMC3, RAD21, and HDAC8) have been associated with CdLS. A diagnosis of RTS or CdLS is molecularly confirmed in only 65% of clinically identified cases, suggesting that additional causative genes exist for both conditions. In addition, although EP300 and CREBBP encode homologous proteins and perform similar functions, only eight EP300 positive RTS patients have been reported, suggesting that patients with EP300 mutations might be escaping clinical recognition. We report on a child with multiple congenital abnormalities and intellectual disability whose facial features and complex phenotype resemble CdLS. However, no mutations in CdLS-related genes were identified. Rather, a novel EP300 mutation was found on whole exome sequencing. Possible links between EP300 and genes causing CdLS are evident in the literature. Both EP300 and HDAC8 are involved in the regulation of TP53 transcriptional activity. In addition, p300 and other chromatin associated proteins, including NIPBL, SMCA1, and SMC3, have been found at enhancer regions in different cell types. It is therefore possible that EP300 and CdLS-related genes are involved in additional shared pathways, producing overlapping phenotypes. As whole exome sequencing becomes more widely utilized, the diverse phenotypes associated with EP300 mutations should be better understood. In the meantime, testing for EP300 mutations in those with features of CdLS may be warranted. © 2013 Wiley Periodicals, Inc.
American journal of medical genetics. Part A.Am J Med Genet A.2014 Jan;164(1):251-8. doi: 10.1002/ajmg.a.36237. Epub 2013 Oct 29.
Rubinstein-Taybi syndrome (RTS) and Cornelia de Lange syndrome (CdLS) are genetically heterogeneous multiple anomalies syndromes, each having a distinctive facial gestalt. Two genes (CREBBP and EP300) are known to cause RTS, and five (NIPBL, SMC1A, SMC3, RAD21, and HDAC8) have been associated with C
PMID 24352918