Substitution mutation

Polymers designed with this technique have a number of important aspects in common with proteins. First of all, the transition from a liquid-like globule into a frozen state occurs as a first order phase transition. Further, the frozen state itself has an essential stability margin, which is determined by the design parameters. As in real proteins, neither a large variation of temperature or other environmental conditions, nor a mutational substitution of several monomers leads to any change in basic state conformation. In this respect the ability of sequence design to capture certain essential characteristics of proteins seems quite plausible. 

Reese, G., Ayuso, R., Leong-Kee, S.M., Plante, M., Lehrer, S.B. 2002. Epitope mapping and mutational substitution analysis of the major shrimp allergen Pen a 1 (tropomyosin). Journal of Allergy and Clinical Immunology 109(1) S307-S307. 

The deletion of a single base from a DNA molecule can be a fatal mutation. Substitution of one base for another is often not as serious a mutation. Why ... 

The author s group has demonstrated that mutations (substitutions of the protein variant) distant from the active site (such as with some of the loops, see Section 7.16.4.1) could have a dramatic influence not only changing the rate, but even changing the rate-limiting step. Therefore, further developments of this method were needed to address these issues on more complex systems such as with the multienzyme complexes. The ThDP-bound intermediates have been synthesized and their chemistry established by the author and others. ... 

An insertion mutation involves the insertion of a base into the normal sequence. A deletion mutation involves the deletion of a base from the normal sequence. Insertion and deletion mutations, referred to as frame shift mutations, are rarer than substitution mutations but can cause much larger effects. A frame shift mutation changes all codons that follows an insertion or deletion in an exon or intron. There is no effect of a mutation (substitution or frame shift) in an intron. The mutation is constrained within the intron and has no effect on the codons in the exons because the introns are excised (Fig 21.10). But a frameshift mutation in an exon yields nonfunctional protein because all codons after the mutation are altered. The polypeptide sequence generally bears no resemblance to that coded in the original DNA. 

Mitochondrial DNA mutation rates in the control region were measured directly by comparing mitochondrial DNA from siblings and from parents and their offspring. Mitochondrial DNA was found to mutate about 20 times faster than previously thought, at an approximate rate of one mutation (substitution) every 33 generations. 

There are three broad categories of mutations substitutions, insertions, and deletions. 

Mutations can be described based on the change in the gene and/or the change in the protein. Standard methods of reporting mutations have been developed [15]. A description of a mutation at the gene level identifies which nucleotide(s) has (have) been changed and type of mutation. Substitutions are denoted by the... 

The random mutation substitutes each gene with a new random one. 

Figure 5 Typical record of an SSCP analysis. Detection of point mutation (substitution of thymine to cytosine) causing phenylketonuria in a heterozygote. Four completely dissociated DNA strands with different sequences (two couples of complementary strands with and without the point mutation) are resolved as four conformers in a native separation environment. The large peak represents a portion of undissociated double-stranded DNA.

SSCP is a popular technique for the screening of mutations or polymorphisms in short segments of DNA. Mutations are detected by monitoring of mobility shifts of individual DNA strands caused by their conformation changes. The main advantage of the SSCP technique is the ability to detect mutations (substitutions, small deletions, and insertions) at a variety of positions in DNA fragments with good... 

Table 1. Average surface accessibilities (x) and the differences of the surface accessibility areas of CIDNP-sensitive residues derived from molecular dynamics calculations between the wild-type of EcorL (x) and the three single-site mutants [7]. All area values are given in A. Dot density 1 test sphere radius 1.5 A. denotes the site of mutation substituting the respective tyrosine residue with CIDNP-inert alanine.

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