DRGAS: DNA Repair Genetic Association Studies

DRGAS is a database of genetic association studies for DNA repair systems. It includes the information for genetic markers, haplotypes, linkage disequilibrium, nsSNP's, mechanisms, repair pathways and related disorders. Numerous diseases comprising of various forms of cancers, aging, xeroderma pigmentosum, cockayne syndrome, werner syndrome, HNPCC and many more have been reported due to genetic variations in repair genes.

DRGAS is a comprehensive and unique database which is very easy to use and implement. It provides efficient access to the repair data with main classification systems. This database can be browsed through various search options:
  • Search by Mechanism
  • Search for Non Synonymous SNPs
  • Search for Haplotypes
  • Search for Linkage Disequilibrium
  • Search for Genetic Marker(s)
  • Search By Disease
  • Search for Phosphorylation Sites
It also provides the facility for Advance Options where one could easily access the entire information regarding a particular entity.

Search by Mechanism and nsSNP's
Mechanism wise search provides you the facility to explore mechanism specific genes with the given set of options. For an example, lets view the details for only those genes that are involoved in Base Excision Repair and then click on Get by Mechanism option. In the case we need to retrieve all the non- synonymous SNP's just for a single gene, Gene ID for the same can be entered in the textbox provided and then Get nsSNPs button can be clicked.

The following result will be displayed for the above mentioned queries.

Search for Haplotypes and Linkage Disequilibrium
One can easily browse through various genetic parameters like Haplotypes and Linkage Disequilibrium from DRGAS based on the unique Gene ID's (from GenBank) for all the DNA repair genes. These options gives you the information on essential haplotype blocks and the non-random association of alleles. Consider the case, where we retrieve the haplotypes for Gene ID as "8930" and click on Get Haplotype button and LD plot for Gene ID as "675" and then click on Get LD option.

The output for the user specified search shows that the Gene ID belongs to MBD4 gene and the haplotype block is representing 7 Markers for the given gene.

In the same way, Gene ID for LD analysis as "675" corresponds to BRCA2 gene. The output shows the relationship between the two loci's on the basis of the correlation between them where only those loci values has been taken whose r2 value is greater than 0.6 . The relationship has been shown in the order of decreasing r2 value, the degree of correlation between the alleles is highest at the top and lowest at the bottom.

Search for Genetic Marker(s) and Disease
Mutations and other genetic abberations in DNA repair genes and its related pathways are responsible for causing a number of diseases like various forms of Cancers, Progeria, Xeroderma pigmentosum,etc. This section is particularly important for disease related information caused by specific repair genes and the genetic markers that are responsible for the diseases. For genetic markers related to a particular gene, Gene ID for that gene can be entered (e.g. 5887) and then Get Marker button can be selected and for DNA repair related information regarding a specific disease can be browsed from the list of a number of diseases provided in the menu (e.g. Xeroderma Pigmentosum) and then Get By Disease option can be selected.

The given Gene ID for genetic marker option belongs to RAD23B and the output shows the entire genetic features for the given gene.

The output of the disease-based search provides the essential details regarding a particular entry which includes Gene name, mechanism in which it is involved, OMIM Id"s, related disorders and associated pathways. Here, all the genes have been retrieved which are involved in Xeroderma Pigmentosum.

Search for Phosphorylation Sites
The Phosphorylation Search box helps the user to retrieve all the important phosphorylated residues in the DNA repair protein sequences. These predictions are based on whether the Serine, Threonine or Tyrosine residues are phosphorylated or not. Let us suppose that MLH1 protein has to be searched for phosphorylation sites,so we enter the gene name in the search box and then click on Get Phos Sites button.

Here,the position gives the location of the residue in the protein sequence, 9 character sequence gives the 9 residue sequence where the phosphorylated residue is represented at the center.The Prediction score above 0.5 gives high probability for phosphorylation site. The residues being phosphorylated are "S", "T" and "Y".

The advanced options provides the facility to search for filtered marker information and the search based on nsSNP.

The nsSNP based search for rs114671957 SNP ID shows that the gene name is NEIL3 and there is a nsSNP at the position 251 where Arginine (R) has been replaced by Histidine (H) and this repalcement has been predicted as damaging from the SIFT algorithm.