DNA polymorphisms as tools for spinal cord injury research.

STUDY DESIGN

Data mining of single nucleotide polymorphisms (SNPs) in gene pathways related to spinal cord injury (SCI).

OBJECTIVES

To identify gene polymorphisms putatively implicated with neuronal damage evolution pathways, potentially useful to SCI study.

SETTING

Departments of Psychiatry and Orthopedics, Faculdade de Medicina, Universidade de São Paulo, Brazil.

METHODS

Genes involved with processes related to SCI, such as apoptosis, inflammatory response, axonogenesis, peripheral nervous system development and axon ensheathment, were determined by evaluating the 'Biological Process' annotation of Gene Ontology (GO). Each gene of these pathways was mapped using MapViewer, and gene coordinates were used to identify their polymorphisms in the SNP database. As a proof of concept, the frequency of subset of SNPs, located in four genes (ALOX12, APOE, BDNF and NINJ1) was evaluated in the DNA of a group of 28 SCI patients and 38 individuals with no SC lesions.

RESULTS

We could identify a total of 95,276 SNPs in a set of 588 genes associated with the selected GO terms, including 3912 nucleotide alterations located in coding regions of genes. The five non-synonymous SNPs genotyped in our small group of patients, showed a significant frequency, reinforcing their potential use for the investigation of SCI evolution.

CONCLUSION

Despite the importance of SNPs in many aspects of gene expression and protein activity, these gene alterations have not been explored in SCI research. Here we describe a set of potentially useful SNPs, some of which could underlie the genetic mechanisms involved in the post trauma spinal cord damage.