what type of mutation leads to a frameshift in the reading of dna

Mutation that shifts codon alignment

Unlike types of indel mutation. Panel C is simply a deletion and not a frameshift mutation.

A frameshift mutation (also called a framing fault or a reading frame shift) is a genetic mutation caused by indels (insertions or deletions) of a number of nucleotides in a Dna sequence that is not divisible by three. Due to the triplet nature of gene expression by codons, the insertion or deletion tin can modify the reading frame (the group of the codons), resulting in a completely different translation from the original. The earlier in the sequence the deletion or insertion occurs, the more than altered the poly peptide.^[1] A frameshift mutation is not the aforementioned every bit a unmarried-nucleotide polymorphism in which a nucleotide is replaced, rather than inserted or deleted. A frameshift mutation volition in general cause the reading of the codons afterwards the mutation to lawmaking for different amino acids. The frameshift mutation will also alter the starting time stop codon ("UAA", "UGA" or "UAG") encountered in the sequence. The polypeptide existence created could be abnormally brusk or abnormally long, and will virtually probable not be functional.^[2]

Frameshift mutations are apparent in severe genetic diseases such as Tay–Sachs disease; they increase susceptibility to certain cancers and classes of familial hypercholesterolaemia; in 1997,^[3] a frameshift mutation was linked to resistance to infection by the HIV retrovirus. Frameshift mutations accept been proposed as a source of biological novelty, equally with the alleged creation of nylonase, however, this estimation is controversial. A study past Negoro et al (2006)^[4] institute that a frameshift mutation was unlikely to take been the cause and that rather a two amino acid exchange in the agile site of an bequeathed esterase resulted in nylonase.

Background [edit]

The data independent in Deoxyribonucleic acid determines protein office in the cells of all organisms. Transcription and translation permit this information to be communicated into making proteins. However, an fault in reading this communication tin can crusade protein role to exist incorrect and eventually cause disease fifty-fifty as the prison cell incorporates a multifariousness of corrective measures.

Central dogma [edit]

In 1956 Francis Crick described the flow of genetic data from DNA to a specific amino acid arrangement for making a poly peptide as the central dogma.^[1] For a cell to properly function, proteins are required to be produced accurately for structural and for catalytic activities. An incorrectly fabricated protein can have detrimental effects on cell viability and in most cases cause the higher organism to get unhealthy past aberrant cellular functions. To ensure that the genome successfully passes the information on, proofreading mechanisms such as exonucleases and mismatch repair systems are incorporated in DNA replication .^[ane]

Transcription and translation [edit]

Subsequently DNA replication, the reading of a selected department of genetic information is accomplished by transcription.^[i] Nucleotides containing the genetic information are now on a unmarried strand messenger template called mRNA. The mRNA is incorporated with a subunit of the ribosome and interacts with an rRNA. The genetic data carried in the codons of the mRNA are now read (decoded) past anticodons of the tRNA. As each codon (triplet) is read, amino acids are existence joined together until a end codon (UAG, UGA or UAA) is reached. At this point the polypeptide (poly peptide) has been synthesised and is released.^[one] For every 1000 amino acid incorporated into the protein, no more than one is wrong. This allegiance of codon recognition, maintaining the importance of the proper reading frame, is achieved by proper base pairing at the ribosome A site, GTP hydrolysis activity of EF-Tu a class of kinetic stability, and a proofreading mechanism as EF-Tu is released.^[1]

Frameshifting may also occur during prophase translation, producing dissimilar proteins from overlapping open reading frames, such as the gag-politician-env retroviral proteins. This is adequately mutual in viruses and likewise occurs in bacteria and yeast (Farabaugh, 1996). Reverse transcriptase, as opposed to RNA Polymerase II, is thought to be a stronger cause of the occurrence of frameshift mutations. In experiments only 3–13% of all frameshift mutations occurred considering of RNA Polymerase II. In prokaryotes the error charge per unit inducing frameshift mutations is only somewhere in the range of .0001 and .00001.^[5]

There are several biological processes that help to forbid frameshift mutations. Contrary mutations occur which modify the mutated sequence back to the original wild type sequence. Some other possibility for mutation correction is the use of a suppressor mutation. This offsets the result of the original mutation by creating a secondary mutation, shifting the sequence to let for the correct amino acids to exist read. Guide RNA can also be used to insert or delete Uridine into the mRNA after transcription, this allows for the right reading frame.^[1]

Codon-triplet importance [edit]

The iii letter lawmaking, the codon

A codon is a set of three nucleotides, a triplet that lawmaking for a certain amino acid. The beginning codon establishes the reading frame, whereby a new codon begins. A protein's amino acid backbone sequence is defined by face-to-face triplets.^[6] Codons are primal to translation of genetic information for the synthesis of proteins. The reading frame is set when translating the mRNA begins and is maintained as it reads 1 triplet to the side by side. The reading of the genetic code is subject area to 3 rules the monitor codons in mRNA. Get-go, codons are read in a 5' to three' direction. Second, codons are nonoverlapping and the message has no gaps. The concluding rule, equally stated above, that the message is translated in a fixed reading frame.^[1]

Instance of different types of point mutations

Mechanism [edit]

Frameshift mutations can occur randomly or be acquired by an external stimulus. The detection of frameshift mutations tin can occur via several different methods. Frameshifts are just 1 type of mutation that tin lead to incomplete or incorrect proteins, simply they account for a meaning percent of errors in Dna.

Genetic or environmental [edit]

This is a genetic mutation at the level of nucleotide bases. Why and how frameshift mutations occur are continually being sought after. An environmental study, specifically the product of UV-induced frameshift mutations by Dna polymerases deficient in 3′ → v′ exonuclease activeness was done. The normal sequence 5′ GTC GTT TTA CAA three′ was changed to GTC GTT T TTA CAA (MIDT) of GTC GTT C TTA CAA (MIDC) to written report frameshifts. E. coli political leader I Kf and T7 DNA polymerase mutant enzymes devoid of 3′ → five′ exonuclease activeness produce UV-induced revertants at higher frequency than did their exonuclease proficient counterparts. The data indicates that loss of proofreading action increases the frequency of UV-induced frameshifts.^[7]

Detection [edit]

Fluorescence [edit]

The furnishings of neighboring bases and secondary construction to detect the frequency of frameshift mutations has been investigated in depth using fluorescence. Fluorescently tagged DNA, by ways of base analogues, permits one to written report the local changes of a DNA sequence.^[8] 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 burl, i.eastward. a structure flanked on both sides by duplex DNA. In contrast, a double-loop structure with an unusual unstacked DNA conformation at its downstream border was observed when the extruded bases were positioned at the primer–template junction, showing that misalignments can be modified by neighboring DNA secondary construction.^[nine]

Sequencing [edit]

A deletion mutation alters every codon following information technology, and can brand protein synthesis end prematurely by forming a stop codon.

Sanger sequencing and pyrosequencing are two methods that have been used to detect frameshift mutations, however, it is likely that data generated will non be of the highest quality. Fifty-fifty notwithstanding, 1.96 million indels take been identified through Sanger sequencing that do not overlap with other databases. When a frameshift mutation is observed it is compared against the Human Genome Mutation Database (HGMD) to determine if the mutation has a damaging effect. This is washed by looking at four features. First, the ratio between the afflicted and conserved Deoxyribonucleic acid, second the location of the mutation relative to the transcript, 3rd the ratio of conserved and afflicted amino acids and finally the distance of the indel to the end of the exon.^[10]

Massively Parallel Sequencing is a newer method that tin be used to discover mutations. Using this method, up to 17 gigabases can be sequenced at once, equally opposed to limited ranges for Sanger sequencing of only nigh i kilobase. Several technologies are available to perform this exam and it is being looked at to exist used in clinical applications.^[11] When testing for different carcinomas, current methods only allow for looking at one factor at a time. Massively Parallel Sequencing can test for a variety of cancer causing mutations at one time as opposed to several specific tests.^[12] An experiment to determine the accuracy of this newer sequencing method tested for 21 genes and had no false positive calls for frameshift mutations.^[13]

Diagnosis [edit]

A US patent (v,958,684) in 1999 by Leeuwen, details the methods and reagents for diagnosis of diseases caused by or associated with a gene having a somatic mutation giving ascent to a frameshift mutation. The methods include providing a tissue or fluid sample and conducting gene analysis for frameshift mutation or a poly peptide from this blazon of mutation. The nucleotide sequence of the suspected gene is provided from published cistron sequences or from cloning and sequencing of the suspect gene. The amino acid sequence encoded past the gene is and then predicted.^[14]

Frequency [edit]

Despite the rules that govern the genetic code and the various mechanisms present in a cell to ensure the correct transfer of genetic information during the process of DNA replication likewise as during translation, mutations exercise occur; frameshift mutation is not the just blazon. In that location are at to the lowest degree two other types of recognized bespeak mutations, specifically missense mutation and nonsense mutation.^[i] A frameshift mutation can drastically change the coding capacity (genetic data) of the message.^[1] Pocket-size insertions or deletions (those less than 20 base pairs) brand up 24% of mutations that manifest in currently recognized genetic disease.^[10]

Frameshift mutations are found to be more than common in repeat regions of DNA. A reason for this is because of slipping of the polymerase enzyme in repeat regions, allowing for mutations to enter the sequence.^[fifteen] Experiments can be run to make up one's mind the frequency of the frameshift mutation by calculation or removing a pre-fix number of nucleotides. Experiments accept been run past adding 4 basepairs, called the +4 experiments, but a team from Emory University looked at the difference in frequency of the mutation by both calculation and deleting a base pair. It was shown that there was no divergence in the frequency betwixt the addition and deletion of a base pair. In that location is however, a deviation in the end result of the protein.^[fifteen]

Huntington's disease is one of the nine codon reiteration disorders caused by polyglutamine expansion mutations that include spino-cerebellar ataxia (SCA) i, 2, 6, 7 and 3, spinobulbar muscular atrophy and dentatorubal-pallidoluysianatrophy. There may be a link between diseases caused by polyglutamine and polyalanine expansion mutations, every bit frame shifting of the original SCA3 gene product encoding CAG/polyglutamines to GCA/polyalanines. Ribosomal slippage during translation of the SCA3 poly peptide has been proposed equally the mechanism resulting in shifting from the polyglutamine to the polyalanine-encoding frame. A dinucleotide deletion or single nucleotide insertion inside the polyglutamine tract of huntingtin exon ane would shift the CAG, polyglutamineen coding frame by +one (+i frame shift) to the GCA, polyalanine-encoding frame and introduce a novel epitope to the C terminus of Htt exon one (APAAAPAATRPGCG).^[16]

Diseases [edit]

Several diseases have frameshift mutations as at least part of the cause. Knowing prevalent mutations can besides aid in the diagnosis of the disease. Currently there are attempts to utilize frameshift mutations beneficially in the treatment of diseases, changing the reading frame of the amino acids.

Frequency of mutations on BRCA1 cistron on chromosome 17

Frequency of mutations on BRCA2 gene on chromosome 13

Cancer [edit]

Frameshift mutations are known to be a gene in colorectal cancer equally well as other cancers with microsatellite instability. As stated previously, frameshift mutations are more likely to occur in a region of repeat sequence. When DNA mismatch repair does not fix the addition or deletion of bases, these mutations are more probable to be pathogenic. This may be in part because the tumor is not told to stop growing. Experiments in yeast and bacteria aid to prove characteristics of microsatellites that may contribute to defective Deoxyribonucleic acid mismatch repair. These include the length of the microsatellite, the makeup of the genetic material and how pure the repeats are. Based on experimental results longer microsatellites have a college rate of frameshift mutations. The flanking DNA tin can likewise contribute to frameshift mutations.^[17] In prostate cancer a frameshift mutation changes the open reading frame (ORF) and prevents apoptosis from occurring. This leads to an unregulated growth of the tumor. While in that location are ecology factors that contribute to the progression of prostate cancer, in that location is as well a genetic component. During testing of coding regions to identify mutations, 116 genetic variants were discovered, including 61 frameshift mutations.^[18] There are over 500 mutations on chromosome 17 that seem to play a role in the development of breast and ovarian cancer in the BRCA1 cistron, many of which are frameshift.^[19]

Crohn's affliction [edit]

Crohn's affliction has an association with the NOD2 cistron. The mutation is an insertion of a Cytosine at position 3020. This leads to a premature terminate codon, shortening the poly peptide that is supposed to be transcribed. When the protein is able to form unremarkably, it responds to bacterial liposaccharides, where the 3020insC mutation prevents the protein from being responsive.^[20]

Cystic fibrosis [edit]

Cystic fibrosis (CF) is a disease based on mutations in the CF transmembrane conductance regulator (CFTR) factor. There are over 1500 mutations identified, but not all cause the disease.^[21] Well-nigh cases of cystic fibrosis are a effect of the ∆F508 mutation, which deletes the unabridged amino acid. Two frameshift mutations are of interest in diagnosing CF, CF1213delT and CF1154-insTC. Both of these mutations commonly occur in tandem with at least one other mutation. They both lead to a small decrease in the function of the lungs and occur in almost one% of patients tested. These mutations were identified through Sanger sequencing.^[22]

HIV [edit]

CCR5 is one of the prison cell entry co-factors associated with HIV, most frequently involved with nonsyncytium-inducing strains, is almost apparent in HIV patients as opposed to AIDS patients. A 32 base of operations pair deletion in CCR5 has been identified every bit a mutation that negates the likelihood of an HIV infection. This region on the open reading frame ORF contains a frameshift mutation leading to a premature stop codon. This leads to the loss of the HIV-coreceptor function in vitro. CCR5-1 is considered the wild type and CCR5-2 is considered to be the mutant allele. Those with a heterozygous mutation for the CCR5 were less susceptible to the development of HIV. In a report, despite high exposure to the HIV virus, there was no one homozygous for the CCR5 mutation that tested positive for HIV.^[three]

Tay–Sachs disease [edit]

Tay–Sachs disease is a fatal disease affecting the cardinal nervous system. It is nearly frequently institute in infants and small children. Disease progression begins in the womb but symptoms do not appear until approximately 6 months of historic period. There is no cure for the disease.^[23] Mutations in the β-hexosaminidase A (Hex A) gene are known to bear upon the onset of Tay-Sachs, with 78 mutations of different types being described, 67 of which are known to cause disease. About of the mutations observed (65/78) are single base substitutions or SNPs, eleven deletions, 1 large and 10 small, and 2 insertions. 8 of the observed mutations are frameshift, 6 deletions and two insertions. A iv base pair insertion in exon 11 is observed in 80% of Tay-Sachs disease presence in the Ashkenazi Jewish population. The frameshift mutations lead to an early stop codon which is known to play a role in the disease in infants. Delayed onset disease appears to be caused by 4 different mutations, one being a iii base pair deletion.^[24]

Smith–Magenis syndrome [edit]

Smith–Magenis syndrome (SMS) is a complex syndrome involving intellectual disabilities, sleep disturbance, behavioural bug, and a variety of craniofacial, skeletal, and visceral anomalies. The bulk of SMS cases harbor an ~3.5 Mb common deletion that encompasses the retinoic acid induced-1 (RAI1) factor. Other cases illustrate variability in the SMS phenotype not previously shown for RAI1 mutation, including hearing loss, absenteeism of cocky-abusive behaviours, and mild global delays. Sequencing of RAI1 revealed mutation of a heptamericC-tract (CCCCCCC) in exon iii resulting in frameshift mutations. Of the vii reported frameshift mutations occurring in poly C-tracts in RAI1, four cases (~57%) occur at this heptameric C-tract. The results indicate that this heptameric C-tract is a preferential recombination hotspot insertion/deletions (SNindels) and therefore a principal target for assay in patients suspected for mutations in RAI1.^[25]

Hypertrophic cardiomyopathy [edit]

Hypertrophic cardiomyopathy is the most common cause of sudden expiry in young people, including trained athletes, and is acquired by mutations in genes encoding proteins of the cardiac sarcomere. Mutations in the Troponin C gene (TNNC1) are a rare genetic cause of hypertrophic cardiomyopathy. A recent study has indicated that a frameshift mutation (c.363dupG or p.Gln122AlafsX30) in Troponin C was the cause of hypertrophic cardiomyopathy (and sudden cardiac death) in a xix-year-old male.^[26]

Cures [edit]

Finding a cure for the diseases acquired past frameshift mutations is rare. Research into this is ongoing. One example is a primary immunodeficiency (PID), an inherited condition which can lead to an increase in infections. There are 120 genes and 150 mutations that play a office in primary immunodeficiencies. The standard treatment is currently gene therapy, but this is a highly risky treatment and can often lead to other diseases, such as leukemia. Factor therapy procedures include modifying the zinc fringer nuclease fusion protein, cleaving both ends of the mutation, which in turn removes it from the sequence. Antisense-oligonucleotide mediated exon skipping is another possibility for Duchenne muscular dystrophy. This process allows for passing over the mutation and so that the rest of the sequence remains in frame and the function of the poly peptide stays intact. This, withal, does not cure the illness, just treats symptoms, and is only practical in structural proteins or other repetitive genes. A third course of repair is revertant mosaicism, which is naturally occurring by creating a reverse mutation or a mutation at a second site that corrects the reading frame. This reversion may happen by intragenic recombination, mitotic cistron conversion, second site Dna slipping or site-specific reversion. This is possible in several diseases, such as X-linked astringent combined immunodeficiency (SCID), Wiskott–Aldrich syndrome, and Bloom syndrome. In that location are no drugs or other pharmacogenomic methods that assistance with PIDs.^[27]

A European patent (EP1369126A1) in 2003 by Bork records a method used for prevention of cancers and for the curative treatment of cancers and precancers such as Dna-mismatch repair deficient (MMR) sporadic tumours and HNPCC associated tumours. The idea is to use immunotherapy with combinatorial mixtures of tumour-specific frameshift mutation-derived peptides to arm-twist a cytotoxic T-prison cell response specifically directed confronting tumour cells.^[28]

References [edit]

^ ^a ^b ^c ^d ^east ^f ¹⁰⁰⁰ ^h ⁱ ^j Losick, Richard; Watson, James D.; Bakery, Tania A.; Bell, Stephen; Gann, Alexander; Levine, Michael W. (2008). Molecular biology of the gene (sixth ed.). San Francisco: Pearson/Benjamin Cummings. ISBN978-0-8053-9592-i.
^ "DNA Is Constantly Irresolute through the Procedure of Mutation". Nature . Retrieved 17 May 2019.
^ ^a ^b Zimmerman PA, Buckler-White A, Alkhatib Thousand, Spalding T, Kubofcik J, Combadiere C, Weissman D, Cohen O, Rubbert A, Lam G, Vaccarezza G, Kennedy PE, Kumaraswami V, Giorgi JV, Detels R, Hunter J, Chopek Chiliad, Berger EA, Fauci AS, Nutman TB, Tater PM (January 1997). "Inherited resistance to HIV-1 conferred by an inactivating mutation in CC chemokine receptor v: studies in populations with contrasting clinical phenotypes, defined racial background, and quantified risk". Molecular Medicine (Cambridge, Mass.). 3 (i): 23–36. PMC2230106. PMID 9132277.
^ Negoro Southward, Ohki T, Shibata Northward, Mizuno N, Wakitani Y, Tsurukame J, Matsumoto K, Kawamoto I, Takeo M, Higuchi Y (November 2005). "Ten-ray crystallographic analysis of half dozen-aminohexanoate-dimer hydrolase: molecular basis for the birth of a nylon oligomer-degrading enzyme". J Biol Chem. 280 (47): 39644–52. doi:x.1074/jbc.m505946200. PMID 16162506.
^ Zhang, J (Baronial 2004). "Host RNA polymerase II makes minimal contributions to retroviral frame-shift mutations". The Journal of General Virology. 85 (Pt 8): 2389–95. doi:10.1099/vir.0.80081-0. PMID 15269381.
^ Cox, Michael; Nelson, David R.; Lehninger, Albert L (2008). Lehninger principles of biochemistry . San Francisco: Westward.H. Freeman. ISBN978-0-7167-7108-1.
^ Sagher, Daphna; Turkington, Edith; Acharya, Sonia; Strauss, Bernard (July 1994). "Product of UV-induced Frameshift Mutations in Vitro by DNA Polymerases Deficient in 3′ → 5′ Exonuclease Action". Journal of Molecular Biology. 240 (3): 226–242. doi:ten.1006/jmbi.1994.1437. PMID 8028006.
^ Johnson, Neil P.; Walter A. Baase; Peter H. von Hippel (March 2004). "Depression-energy circular dichroism of 2-aminopurine dinucleotide as a probe of local conformation of Dna and RNA". Proc Natl Acad Sci U S A. 101 (ten): 3426–31. Bibcode:2004PNAS..101.3426J. doi:x.1073/pnas.0400591101. PMC373478. PMID 14993592.
^ Baase, Walter A.; Davis Jose; Benjamin C. Ponedel; Peter H. von Hippel; Neil P. Johnson (2009). "Deoxyribonucleic acid models of trinucleotide frameshift deletions: the formation of loops and bulges at the primer–template junction". Nucleic Acids Research. 37 (5): 1682–nine. doi:10.1093/nar/gkn1042. PMC2655659. PMID 19155277.
^ ^a ^b Hu, J; Ng, PC (9 February 2012). "Predicting the effects of frameshifting indels". Genome Biology. 13 (2): R9. doi:10.1186/gb-2012-13-ii-r9. PMC3334572. PMID 22322200.
^ Tucker, Tracy; Marra, Marco; Friedman, January M. (2009). "Massively Parallel Sequencing: The Next Big Thing in Genetic Medicine". The American Journal of Human Genetics. 85 (two): 142–154. doi:ten.1016/j.ajhg.2009.06.022. PMC2725244. PMID 19679224.
^ Walsh, T.; Casadei, Southward.; Lee, M. M.; Pennil, C. C.; Nord, A. Southward.; Thornton, A. M.; Roeb, W.; Agnew, M. J.; Devious, S. M.; Wickramanayake, A.; Norquist, B.; Pennington, K. P.; Garcia, R. L.; King, One thousand.-C.; Swisher, E. M. (2011). "From the Cover: Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing". Proc Natl Acad Sci U S A. 108 (44): 18032–7. Bibcode:2011PNAS..10818032W. doi:x.1073/pnas.1115052108. PMC3207658. PMID 22006311.
^ Walsh, T.; Lee, M. K.; Casadei, S.; Thornton, A. M.; Stray, South. Yard.; Pennil, C.; Nord, A. S.; Mandell, J. B.; Swisher, E. Thousand.; King, G.-C. (2010). "Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing". Proc Natl Acad Sci U Southward A. 107 (28): 12629–33. Bibcode:2010PNAS..10712629W. doi:10.1073/pnas.1007983107. PMC2906584. PMID 20616022.
^ US Patent 5,958,684 (September 28, 1999) "Diagnosis of Neurodegenerative Disease" by Leeuwen et al
^ ^a ^b Harfe, BD; Jinks-Robertson, Southward (July 1999). "Removal of frameshift intermediates past mismatch repair proteins in Saccharomyces cerevisiae". Molecular and Cellular Biology. 19 (seven): 4766–73. doi:10.1128/MCB.19.vii.4766. PMC84275. PMID 10373526.
^ Davies, J East; Rubinsztein, D C (2006). "Polyalanine and polyserine frameshift products in Huntington's disease". Journal of Medical Genetics. 43 (11): 893–896. doi:ten.1136/jmg.2006.044222. PMC2563184. PMID 16801344.
^ Schmoldt, A; Benthe, HF; Haberland, Thou (one September 1975). "Digitoxin metabolism by rat liver microsomes". Biochemical Pharmacology. 24 (17): 1639–41. doi:x.1016/0006-2952(75)90094-five. PMID 10.
^ Xu, XiaoLin; Zhu, KaiChang; Liu, Feng; Wang, Yue; Shen, JianGuo; Jin, Jizhong; Wang, Zhong; Chen, Lin; Li, Jiadong; Xu, Min (May 2013). "Identification of somatic mutations in human prostate cancer past RNA-Seq". Gene. 519 (2): 343–7. doi:10.1016/j.gene.2013.01.046. PMID 23434521.
^ "Cancer Genomics". National Cancer Found at the National Constitute of Health. Archived from the original on xviii March 2013. Retrieved 24 March 2013.
^ Ogura Y, Bonen DK, Inohara North, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nuñez M, Cho JH (May 31, 2001). "A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease" (PDF). Nature. 411 (6837): 603–6. Bibcode:2001Natur.411..603O. doi:x.1038/35079114. hdl:2027.42/62856. PMID 11385577. S2CID 205017657.
^ Farrell PM, Rosenstein BJ, White TB, Accurso FJ, Castellani C, Cutting GR, Durie PR, Legrys VA, Massie J, Parad RB, Stone MJ, Campbell PW (2008). "Guidelines for Diagnosis of Cystic Fibrosis in Newborns through Older Adults: Cystic Fibrosis Foundation Consensus Report". The Journal of Pediatrics. 153 (2): S4–S14. doi:10.1016/j.jpeds.2008.05.005. PMC2810958. PMID 18639722.
^ Iannuzzi, MC; Stern, RC; Collins, FS; Hon, CT; Hidaka, N; Stiff, T; Becker, L; Drumm, ML; White, MB; Gerrard, B (February 1991). "Ii frameshift mutations in the cystic fibrosis gene". American Journal of Man Genetics. 48 (2): 227–31. PMC1683026. PMID 1990834.
^ "Learning About Tay-Sachs Affliction". National Human Genome Research Institute. Retrieved 24 March 2013.
^ Myerowitz, R (1997). "Tay-Sachs illness-causing mutations and neutral polymorphisms in the Hex A gene". Homo Mutation. 9 (iii): 195–208. doi:10.1002/(SICI)1098-1004(1997)9:3<195::Assist-HUMU1>3.0.CO;ii-7. PMID 9090523.
^ Truong, Hoa T; Dudding, Tracy; Blanchard, Christopher L.; Elsea, Sarah H (2010). "Frameshift mutation hotspot identified in Smith-Magenis syndrome: case report and review of literature". BMC Medical Genetics. xi (1): 142. doi:10.1186/1471-2350-11-142. PMC2964533. PMID 20932317.
^ Chung WK, Kitner C, Maron BJ (June 2011). "Novel frameshift mutation in Troponin C ( TNNC1) associated with hypertrophic cardiomyopathy and sudden expiry". Cardiol Young. 21 (3): 345–eight. doi:10.1017/S1047951110001927. PMID 21262074. S2CID 46682245.
^ Hu, Hailiang; Gatti, Richard A (2008). "New approaches to treatment of main immunodeficiencies: fixing mutations with chemicals". Electric current Stance in Allergy and Clinical Immunology. 8 (6): 540–6. doi:x.1097/ACI.0b013e328314b63b. PMC2686128. PMID 18978469.
^ European Patent [i] (December 10, 2003) "Use of coding microsatellite region frameshift mutation-derived peptides for treating cancer" past Bork et al

External links [edit]

Frameshift+Mutation at the US National Library of Medicine Medical Discipline Headings (MeSH)
NCBI dbSNP database — "a central repository for both unmarried base nucleotide substitutions and short deletion and insertion polymorphisms"
Wise2 - aligns a protein against a Deoxyribonucleic acid sequence allowing frameshifts and introns
FastY - compare a DNA sequence to a poly peptide sequence database, allowing gaps and frameshifts
Path - tool that compares two frameshift proteins (back-translation principle)
HGMD - Human Genome Mutation Database

holtnorly1974.blogspot.com

Source: https://en.wikipedia.org/wiki/Frameshift_mutation