Genetics substitution mutation

It is now believed that a substantial proportion of the single nucleotide substitutions causing human genetic disease are due to misincorporation of bases during DNA replication. Which proofreading activity is critical in determining the accuracy of nuclear DNA replication and thus the base substitution mutation rate in human chromosomes ... 

So far, we have only considered mutations in which the genetic code is kept in strict register. As is commonly known, the genetic code is read in triplets, such that three nucleotides are read together to specify one specific amino acid. With base substitution mutations, only one base is changed, so the amino acid specified by the new triplet nucleotide specifies a new amino acid. However, the rest of the nucleotide... 

Mutations occur by substitution, insertion, or deletion of bases. Substitution mutations are the most common types of mutation. A substitution mutation, involving the substitution of one base by another, changes one codon in mRNA. This may or may not alter the amino acid residue specified by that codon because of the degeneracy of the genetic code. 

Techniques for separation of DNA and RNA provide powerful tools for the analysis of genetic material and transcription products. Modem methods of analysis can answer most of the questions about the sequence, nucleotide substitutions (mutations, polymorphisms, or single nucleotide polymorphisms -SNPs), and stmcture of nucleic acids. Crucial techniques in the analysis of DNA or RNA are the... 

W.M. (2000) An Introduction to Genetic Analysis, W.H. Freeman, New York. Topal, M.D. and Fresco, J.R. (1976) Complementary base-pairing and origin of substitution mutations. Nature, 263 (5575), 285-289. 

Tvrdik T et al Molecular characterization of two deletion events involving Alu-sequences, one novel base substitution and two tentative hotspot mutations in the hypoxanthine phosphori-bosyltransferase gene in five patients with Lesch-Nyhan-syndrome. Hum Genet 1998 103 3H. 

Up to now, 101 different mutations have been identified (Fig. 11) (B29, H18). Most of the variant enzymes are produced by one or two missense mutations in the structural gene. G6PD Vancouver is caused by three nucleotide substitutions (M4). Although nucleotide deletions or nonsense mutations are common molecular abnormalities that may cause a variety of genetic disorders, they are rare in G6PD deficiency cases. Nucleotide deletions have been found in only five variants... 

A base substitution can also result in the formation of a new inappropriate terminator (or non-sense) codon, and are thus known as non-sense mutations. The polypeptide formed from such mutated genes will be shorter than normal and is most likely to be inactive. Owing to the redundancy of the genetic code, about a quarter of all possible base substitutions will not result in an amino acid replacement and will be silent mutations. 

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