Mutations types

Vuorio AF, Ojala JP, Sarna S, Turtola H, Tikkanen MJ, Kontula K. Heterozygous familial hypercholesterolaemia the influence of the mutation type of the low-density-lipoprotein receptor gene and PvuII polymorphism of the normal allele on serum lipid levels and response to lo-vastatin treatment. J Intern Med 1995 237 43-48. 

Mutation type Sample Cancer type LOH Reference... 

Table 2.1. Sequence context of mutation types and their frequencies observed after application of error-prone PCR as described herein and sequencing of cloned genes. Targets T7 RNAP, coding sequence of T7 RNA polymerase, Poll, coding sequence of E. coli DNA polymerase I, Inti on, cDNA of Tetrahymena thermophila intron,...

Becker J, Schwaab R, Moller-Taube A, Schwaab U, Schmidt W, Brackmann HH, Grimm T, Olek K, Oldenburg J. Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A family studies indicate a mutation type-dependent sex ratio of mutation frequencies. Am J Hum Genet 1996 58(4) 657-670. 

Fig. 14. Examples of homogeneous hybridization assay methods (F luminophore, Q quencher, D donor, A acceptor). Thick lines represent DNA strands. Open circles on DNA strands indicate a SNP/mutation site for Molecular Beacon and insertion/deletion sites for dual FRET probe and dual FRET Molecular Beacon when these methods are applied to SNP/mutation typing or deletion/insertion detection. The solid circle on die strand indicates the complementary site.

In addition to cancer, too little apoptosis can also result in diseases such as autoimmune lymphoproliferative syndrome (ALPS). This occurs when there is insufficient apoptosis of auto-aggressive T cells, resulting in multiple autoimmune diseases. An overproliferation of B cells occurs as well, resulting in excess immunoglobulin production, leading to autoimmunity. Some of the common diseases of ALPS include hemolytic anemia, immune-mediated thrombocytopenia, and autoimmune neutropenia. The different types of this condition are caused by different mutations. Type 1A results from a mutation in the death domain of the Fas receptor, Type IB results from a mutation in Fas ligand, and Type 2 results from a mutation in caspase 10, reducing its activity. 

It follows that the technique is useful to identify (1) point mutation (a single different nucleotide) that may be a silent mutation (also known as a synonymous mutation due to degenerate coding), resulting in a codon that codes for the same amino acid or a missense mutation (type of non-synonymous mutation) producing a codon that codes for a different amino acid the resulting protein may be non-functional but certain missense mutations can be quiet since the protein may stiU function polymorphisms, (3) insertions, and deletions. 

Because of the difference in prevalence of inhibitors in hemophilia B and hemophilia A, it has been postulated that there is a correlation between mutation type and inhibitor risk (6). Of the patients with gross deletion, nonsense, or frameshift mutations, 11% developed inhibitors compared with 0% and 0.36% of patients with hemophilia B with mis-sense or other mutations. 

Anaphylaxis in conjunction with inhibitor development has been described. Patients with hemophilia B with complete gene deletions have the greatest risk of anaphylaxis, with a minimum risk of 26%, whereas the risk in patients with null mutations was 2.4% and nearly zero for mis-sense mutations (13). Predisposing factors for the development of anaphylaxis, besides mutation type, are genetic predisposition and environmental experience, such as the type and frequency of factor IX product (13). 

Animal Frequency of ras mutations Type Nucleotide base substitutions C-A A-G A-T A-C G-A... 

Functional consequences of each mutation type vary. Generally, mutations result in either activation of the gene, typically forming an oncogene (e.g., KRAS, RET), or loss of function of a tumor suppressor gene TP53, PTEN, CDKNIA). 

There are a number of techniques available to detect point mutations and small deletions and insertions. In practice, the choice of method depends on mutation type, location (a known hot spot versus randomly distributed mutations), required sensitivity, specimen type, and test volume. 

Singer S, Rubin BP, Lux ML, et al. Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors. / Clin Oncol. 2002 20 3898-3905. 

The amino acid sequence of the beginning of the polypeptide is Met-Ser-Pro-Thr-Ala-Asp-Glu-Gly-Arg-Arg-Trp-Leu-Ile- Met-Phe. The mutation types in the altered mRNA sequences are (a) insertion of one base, (b) deletion of one base, (c) insertion of two bases, (d) deletion of three bases. The consequences of these mutations are altered amino acid sequences of the polypeptides produced from mRNA. In (a), (b), and (c) a frame shift occurs. Therefore the amino acid sequences past the mutation are different. In (d) no frame shift occurs because three bases are deleted. In this case, the only difference between the normal polypeptide and the mutated version is the deletion of a single amino acid. 

Fig. 3A Role of exogenous and endogenous factors in shaping tumor mutation patterns. Mini-hotspots in the p53 coding sequence. Distribution of four mutation types in the coding sequence, GC to AT transitions at CpG (representing 23% of all mutations), GC to TA transversions (15%), GC to CG (8%), and AT to GC (12%). CpG transitions primarily appear as the consequence of an endogenous mutation mechanism and form well-defined mutation hotspots. Because of these major hotspots, the mini-hotspots corresponding to other mutation types are difficult to detect. Only sites that contain more than 1 % of a specific mutation type are shown. Hotspot codons for each mutation type are indicated. Some of the non-CpG hotspots are well-characterized sites of alteration induced by exogenous carcinogens (see Fig. 5).

Protein Organism Mutation Type of Spectra Peak wai (n Ex. length s m) Em. EC QY rel. spec. FL Ref... 

Metal Mutagens Test systems (mutation type) Metal Mutagens Test systems (mutation type)... 

Table 6.9. Types of genetic mutations in hereditary diseases. Mutations are listed by ease of detection from compliant to refractory. Piacticality, the relative ease of detecting a given mutation type will depend on the specific genetic alterations present and the detection methods used [Refs in 355].

Strains/allele Mutation type DNA target Reversion event... 

Each individual is replicated into a new population. Each offspring is mutated according to a distribution of mutation types, from minor to extreme. The severity of mutations is often reduced as the global optimum is... 

Gene Type of mutation Type of mosaic Sex Strain origin Ratio of normal mutant gametes... 

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