In silico analysis of TTR gene (coding and non-coding regions, and interactive network) and its implications in transthyretin-related amyloidosis.
BACKGROUND
Transthyretin (TTR)-related amyloidosis is a life-threatening disease. Currently, several questions about the pathogenic mechanisms of TTR-related amyloidosis remain unanswered.


METHODS
We have investigated various TTR-related issues using different in silico approaches.


RESULTS
Using an amino acid similarity-based analysis, we have indicated the most relevant TTR secondary structures in determining mutation impact. Our amyloidogenic propensity analysis of TTR missense substitutions has highlighted a similar pattern for wild-type and mutated TTR amino β acid sequences. However, some mutations present differences with respect to the general distribution. We have identified non-coding variants in cis-regulatory elements of the TTR gene, and our analysis on V122I-related haplotypes has indicated differences in non-coding regulatory variants, suggesting differences among V122I carriers. The analysis of methylation status indicated CpG sites that may affect TTR expression. Finally, our interactive network analysis revealed functional partners of TTR that may play a modifier role in the pathogenesis of TTR-related amyloidosis.


CONCLUSIONS
Our data provided new insights into the pathogenesis of TTR-related amyloidosis that, if they were to be confirmed through experimental investigations, could significantly improve our understanding of the disease.
Department of Biology, University of Rome "Tor Vergata" , Rome , Italy and.
Renato
R
Polimanti
Marco
M
Di Girolamo
Dario
D
Manfellotto
Maria
M
Fuciarelli
D000465:Algorithms; D028227:Amyloid Neuropathies, Familial / Q000235:genetics* / Q000473:pathology; D003198:Computer Simulation; D018899:CpG Islands; D019175:DNA Methylation; D030541:Databases, Genetic; D044127:Epigenesis, Genetic; D006239:Haplotypes; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D016366:Open Reading Frames; D011228:Prealbumin / Q000737:chemistry / Q000235:genetics*; D025941:Protein Interaction Mapping; D017433:Protein Structure, Secondary; D040681:Structural Homology, Protein; D020506:Untranslated Regions
D011228:Prealbumin; D020506:Untranslated Regions
Amyloidogenic propensity; V122I mutation; bioinformatics; cis-regulatory elements; interactive network