Nucleotide substitution

Examples of a polymorphism include single nucleotide substitutions, insertions and deletions of nucleotides, and repetitive sequences. While most polymorphisms are harmless and part of normal human genetic variations, studies have established links between certain gene polymorphisms and metabolic alterations or human diseases. 

Fig. 3. Phylogenetic relationship of strain BMEL-2 and related taxa, based on D1/D2 region sequence of the large-subunit rDNA. Bar, 0.01 nucleotide substitution per position.

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... 

Eighty distinct mutations in type I AT deficiency, ranging from single nucleotide substitutions, to deletion or insertion of a small number of nucleotides of 22 base pairs or less, to major deletions of either a part of or the entire AT gene, have been recognized (83). 

Polymorphism A common (i.e., at least 1% prevalence of the minor allele in the population) sequence variation observed in an individual at a polymorphic site. Polymorphisms include nucleotide substitutions, insertions, deletions and microsatellites. They may be functional or silent, i.e., they do not result in detectable differences in gene expression or protein function. 

Hughes, A.L. and Nei, M. (1988) Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 335, 167-170. 

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 ... 

The severe form of alpha-1 antitrypsin deficiency is the result of a single nucleotide substitution that produces a single amino acid substitution. This is best described as a... 

An in-frame mutation (choice B) is the insertion or deletion of a multiple of three nucleotides, so this single-nucleotide substitution cannot be an in-frame mutation. 

A nonsense mutation (choice D) is a single nucleotide substitution that produces a stop codon and thus truncation of the polypeptide. Therefore, it typically alters more than a single amino acid. 

In eukaryotes, the existence of compositional biases is unclear and most attempts to detect the replication origins from strand compositional asymmetry have been inconclusive. Several studies have failed to show compositional biases related to replication, and analysis of nucleotide substitutions in the region of the -globin replication origin in primates do not support the existence of mutational bias... 

Z. Zhang, and M. Gerstein, Patterns of nucleotide substitution, insertion and deletion in the human genome inferred from pseudogenes. Nucleic Acids Res. 31, 5338-5348 (2003). 

Utilising a reversion assay in Salmonella enterica, Prieto et al reported an increased frequency of point mutations following bile-salt exposure. Mutations were predominantly nucleotide substitutions (GC to AT transitions) and -1 frameshift mutations.The frameshifts were dependent on SOS induction and linked to the activity of DinB polymerase (Pol IV). The authors proposed that the GC to AT transitions stimulated by bile, could have arisen from oxidative processes giving rise to oxidised cytosine residues. Consistent with this hypothesis, the authors demonstrated that strains of S. enterica-lacking enzymes required for base-excision repair (endonuclease III and exonuclease IV) and the removal of oxidised bases, demonstrated increased bile-acid sensitivity compared with competent strains. In another study using E. coli, resistance to the DNA-damaging effects of bile was associated with Dam-directed mismatch repair, a pathway also involved with the repair of oxidative DNA lesions. ... 

FcyRllla is expressed on macrophages, natural killer cells, and some dendritic cells as a transmembrane receptor. The major polymorphism of Fc RIIIa gene is a single nucleotide substitution at position 559 resulting in the presence of either valine (VI58) or phenylalanine (F158) at position 158 in the extracellular domain (41,42). 

Green L, Waugh S, Binkley JP, Hostomska Z, Hostomsky Z, Tuerk C. Comprehensive chemical modification interference and nucleotide substitution analysis of an RNA pseudoknot inhibitor to HIV-1 reverse transcriptase. J Mol Biol 1995 247 60-68. 

Van de Peer, Y., Chapelle, S. and De Wachter, R. (1 996) A quantitative map of nucleotide substitution rates in bacterial rRNA. Nucleic Acids Research 24, 3381-3391. 

K7. Kovalenko, S. A., Tanaka, M., Yoneda, M., Iakovlev, A. F., and Ozawa, T., Accumulation of somatic nucleotide substitutions in mitochondrial DNA associated with the 3243 A-to-G tRNALe" UURl mutation in encephalomyopathy and mitochondrial myopathy. Biochem. Biophys. Res. Commun. 222, 201-207 (1996). 

In addition to single-nucleotide substitutions or small insertions or deletions detected by DNA sequencing, rtPCR or SNP arrays, different sources of... 

In summary, from the simplest nucleotide substitution to the complex whole-genome analysis, Genomics has developed tools which discover and measure to the highest precision any possible alteration of genomes, transcrip-tomes, or epigenomes, making available an invaluable tool to explain and eventually find a way to treat cancer. 

Yang F, Hanson NQ, Schwichtenberg K, Tsai MY. Variable number tandem repeat in exon/intron border of the cystathionine beta-synthase gene a single nucleotide substitution in the second repeat prevents multiple alternate splicing. Am J Med Genet 2000 95 385-390. 

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