Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Oct 14;16(10):24295-301.
doi: 10.3390/ijms161024295.

Mutational Spectrum Analysis of Neurodegenerative Diseases and Its Pathogenic Implication

Liang Shen  1 , Hong-Fang Ji  2
Affiliations

Mutational Spectrum Analysis of Neurodegenerative Diseases and Its Pathogenic Implication

Liang Shen et al. Int J Mol Sci. .

Abstract

One of the most conspicuous features of neurodegenerative diseases (NDs) is the occurrence of dramatic conformation change of individual proteins. We performed a mutational spectrum analysis of disease-causing missense mutations in seven types of NDs at nucleotide and amino acid levels, and compared the results with those of non-NDs. The main findings included: (i) The higher mutation ratio of G:C→T:A transversion to G:C→A:T transition was observed in NDs than in non-NDs, interpreting the excessive guanine-specific oxidative DNA damage in NDs; (ii) glycine and proline had highest mutability in NDs than in non-NDs, which favor the protein conformation change in NDs; (iii) surprisingly low mutation frequency of arginine was observed in NDs. These findings help to understand how mutations may cause NDs.

Keywords: conformation change; distribution pattern; mutation; neurodegenerative diseases; pathogenesis.

PubMed Disclaimer

Figures

Figure 1
Figure 1
(a) The distribution of nucleotide substitution types and their proportions of NDs in comparison with non-NDs; (b) The amino-acid substitution spectrum of disease-causing missense mutations in NDs and non-NDs.
Figure 1
Figure 1
(a) The distribution of nucleotide substitution types and their proportions of NDs in comparison with non-NDs; (b) The amino-acid substitution spectrum of disease-causing missense mutations in NDs and non-NDs.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Krawczak M., Cooper D.N. The human gene mutation database. Trends Genet. 1997;13:121–122. doi: 10.1016/S0168-9525(97)01068-8. - DOI - PubMed
    1. Wang Z., Moult J. SNPs, protein structure, and disease. Hum. Mutat. 2001;17:263–270. doi: 10.1002/humu.22. - DOI - PubMed
    1. Naya H., Romero H., Zavala A., Alvarez B., Musto H. Aerobiosis increases the genomic guanine plus cytosine content (GC%) in prokaryotes. J. Mol. Evol. 2002;55:260–264. doi: 10.1007/s00239-002-2323-3. - DOI - PubMed
    1. Wang J., Xiong S., Xie C., Markesbery W.R., Lovell M.A. Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer’s disease. J. Neurochem. 2005;93:953–962. doi: 10.1111/j.1471-4159.2005.03053.x. - DOI - PubMed
    1. Nunomura A., Perry G., Aliev G., Hirai K., Takeda A., Balraj E.K., Jones P.K., Ghanbari H., Wataya T., Shimohama S., et al. Oxidative damage is the earliest event in Alzheimer disease. J. Neuropathol. Exp. Neurol. 2001;60:759–767. - PubMed

Publication types

MeSH terms