Zardón NMÁ, Sautié CM, Camayd VI, González QY, Hernández CJL

Language: Spanish
References: 20
Page: 19-28
PDF size: 497.52 Kb.

ABSTRACT

Microsatellites are short tandem repeats that represent the 3 % of the human genome. At present, more than 40 neurological, neurodegenerative, muscular and other diseases associated with the mutational instability of this kind of sequences are known. Gene Ontology may be a very useful tool for studying the functional role of these repetitive sequences and to get an insight into the molecular etiology of these diseases. In this study, the frequency distributions of mononucleotide repeats in coding and non-coding sequences for nearly all genes from the human genome were examined. All the cellular components, molecular functions and biological processes associated with the genes that have the longest repeats were investigated. As a general rule, the statistically significant gene ontology categories investigated corresponded to the nucleic acids, basically those related to the transcription, the cell cycle regulation, the muscular processes, the receptors linked to signals transduction and synapses, as well as those involved in the development of the Central Nervous System. Few significant two and three gene ontology combinations were found and they were predominantly related to nucleic acids. This work will be helpful to establish the normality distributions patterns of repeats associated with the main gene ontology terms, a valuable information for determining and understanding the size threshold of short tandem repeats associated with the risk to contract certain diseases.

REFERENCES

1. Venter, J.C., and coll. The sequence of the human genome. Science. 2001; 291(5507):1304-51.

2. Subirana, J.A. and Messeguer X. Structural families of genomic microsatellites. Gene. 2008; 408(1-2):124-32.

3. Li, Y. C., Korol, A. B. Fahima T., Beiles A., and Nevo E. Microsatellites Within Genes: Structure, Funtion, and Evolution. A review. Mol Ecol. 2004;11:2453-65.

4. Fondon, J.W., Hammock E.A.D., Hannan A. J. and King D. G. Simple sequence repeats: genetic modulators of brain function and behavior. Trends Neurosci. 2008; 31(7):328-34.

5. Kruglyak, S., Durrett T., Schug D. and Aquadro C.F. Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations. Proc. Natl. Acad. Sci. USA 1998; (95):10774-78.

6. Aquilina, G. and Bignami M. Mismatch repair in correction of replication errors and processing of DNA damage. Journal of Cell Physiology. 2001;187:145-54.

7. Hussein, M.R. and Wood G.S. Building bridges in cancer: mismatch repair and microsatellite instability. American Journal of Dermatopathology. 2002; 24:76-81.

8. Pearson, C.E., Nichol Edamura K., and Cleary J.D., Repeat instability: mechanisms of dynamic mutations. Nat Rev Genet. 2005; 6(10):729-42.

9. Madsen, B.E., Villesen P., and Wiuf C., Short bloques repeats in human exons: a target for disease mutations. BMC Genomics. 2008; 9: p. 410.

10. Subramanian, S., Madgula V. M., George R., Mishra R. K., Pandit M., Kumar C. S., Singh S and coll. Triplet repeats in human genome: distribution and their association with genes and other genomic regions. Bioinformatics. 2003; 19(5):549-52.

11. Subramanian, S., Mishra R.K., and Singh L. Genomewide analysis of microsatellite repeats in humans: their abundance and density in specific genomic regions. Genome Biol. 2003; 4(2):R13.

12. Alba, M.M. and Guigo R. Comparative analysis of amino acid repeats in rodents and humans. Genome Res. 2004;14(4):549-54.

13. Rhee, S.Y., Wood V., Dolinski K., and Draghici S. Use and misuse of the gene ontology annotations. Nat Rev Genet. 2008;9(7): 509-15.

14. Drãghici S., Khatri P., Martins R., Ostermeier GC. and Krawetz SA. Global functional profiling of gene expression. Genomics. 2003, 81:98-104.

15. Rose, O., and Falush D.: A threshold size for microsatellite expansion. Mol. Biol. Evol. 1998;15:613-615.

16. Lai, J. and Fengzhu S. The Relationship Between Microsatellite Slippage Mutation Rate and the Number of Repeat Units. Mol. Biol. Evol. 2003;20(12):2123-31.

17. Calabrese, P. and Durrett R. Dinucleotides repeats in the Drosophila and Human genome have complex, length dependent mutation processes. Mol. Biol. Evol. 2003; 20:715-725.

18. Coenye, T. and Vandamme P. Characterization of Mononucleotide Repeats in Sequenced Prokaryotic. Genomes. 2005;85:105-107.

19. Bell, G. I. and Jurka J. The Length Distribution of Perfect Dimer Repetitive DNA Is Consistent with Its Evolution by an Unbiased Single-Step Mutation Process. J. Mol. Evol. 1997;44:414-21.

20. Parniewski P. and Staczec P. Molecular mechanisms of TNR instability. Adv. Exp. Med. Biol. 2002; 516:1-25.