Abstract
We present a comparative analysis of PARK2 genetic variants based on genotype data from HapMap. We focused our study on the association between missense mutations and all other variations within the same gene to uncover patterns of hidden genetic variation. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the main neurodegenerative diseases and represent a growing health concern worldwide, with the increase in the elderly population. Mutations in several genes have been associated with either AD or PD, and the number of novel genetic variants characterized is expanding rapidly with the introduction of next generation sequencing technologies. Most of these variants, however, are of unknown consequences as their effect might be mediated through association with additional mutations. Our results show that significant correlation between genetic variants exists and their co-occurrence might contribute to previously unidentified risk increase.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Corti, O., Lesage, S., Brice, A.: What genetics tells us about the causes and mechanisms of Parkinson’s disease. Physiol. Rev. 91(4), 1161–1218 (2011)
Nuytemans, K., et al.: Genetic etiology of Parkinson disease associated with mutations in the SNCA, PARK2, PINK1, PARK7, and LRRK2 genes: a mutation update. Hum. Mutat. 31(7), 763–780 (2010)
Schellenberg, G.D., Montine, T.J.: The genetics and neuropathology of Alzheimer’s disease. Acta Neuropathol. 124(3), 305–323 (2012)
Trempe, J.F., et al.: Structure of parkin reveals mechanisms for ubiquitin ligase activation. Science 340(6139), 1451–1455 (2013)
Scholz, S.W., et al.: Genomics and bioinformatics of Parkinson’s disease. Cold Spring Harb. Perspect. Med. 2(7), a009449 (2012)
Altshuler, D.M., et al.: Integrating common and rare genetic variation in diverse human populations. Nature 467(7311), 52–58 (2010)
Flicek, P., et al.: Ensembl 2013. Nucleic Acids Res. 41(Database issue), D48–D55 (2013)
Boedigheimer, M.: Fisher’s Exact Test. MATLAB Central File Exchange (2008)
Barrett, J.C., et al.: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21(2), 263–265 (2005)
Hartl, D.L., Clark, A.G.: Principles of Population Genetics, 4th edn. S. Associates, Sunderland (2007)
Kim, S.Y., et al.: Phase analysis identifies compound heterozygous deletions of the PARK2 gene in patients with early-onset Parkinson disease. Clin. Genet. 82(1), 77–82 (2012)
Riley, B.E., et al.: Structure and function of Parkin E3 ubiquitin ligase reveals aspects of RING and HECT ligases. Nat. Commun. 4, 1982 (2013)
Hindorff, L.A., et al.: Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc. Natl. Acad. Sci. USA 106(23), 9362–9367 (2009)
Baralle, D., Baralle, M.: Splicing in action: assessing disease causing sequence changes. J. Med. Genet. 42(10), 737–748 (2005)
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer International Publishing Switzerland
About this paper
Cite this paper
Castro, L., Oliveira, J.L., Silva, R.M. (2014). Mutation Analysis in PARK2 Gene Uncovers Patterns of Associated Genetic Variants. In: Saez-Rodriguez, J., Rocha, M., Fdez-Riverola, F., De Paz Santana, J. (eds) 8th International Conference on Practical Applications of Computational Biology & Bioinformatics (PACBB 2014). Advances in Intelligent Systems and Computing, vol 294. Springer, Cham. https://doi.org/10.1007/978-3-319-07581-5_18
Download citation
DOI: https://doi.org/10.1007/978-3-319-07581-5_18
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-07580-8
Online ISBN: 978-3-319-07581-5
eBook Packages: EngineeringEngineering (R0)