Fabry:Mapping point mutations/Journal

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Fabry Disease » Mapping point mutations » Journal


We search for our gene GLA, followed the button to missense/nonsense mutations, and saved to HTML to a local file, e.g. hgmd_fabry_mutations.html. Afterwards, the file was reformatted to a wiki table with

$ bash hgmd2wikitable.sh hgmd_fabry_mutations.html > hgmd.wikitable

and the SNPs were extracted to a generic parseable format. To convert the three letter representation of the amino acids, the perl script three2one.pl was applied.

$ bash hgmd_extract_mutations.sh hgmd_fabry_mutations.html > hgmd_snps_3.txt
$ perl three2one.pl hgmd_snps_3.txt > hgmd_snps.txt


The dbSNP was searched for silent mutations using the following search string

"synonymous-codon"[Function_Class] AND GLA[GENE] AND "human"[ORGN] AND "snp"[SNP_CLASS]

and the results page was saved as locally as "synonymous-codon"[Function_Class] AND GLA[GENE] AND "human"[ORGN] AND "snp"[SNP_CLASS] - SNP Results.html.

Eventually, the SNPs were extracted to a generic parseable format. To convert the three letter representation of the amino acids, the perl script three2one.pl was applied.

$ bash parse_dbSNP.sh '"synonymous-codon"[Function_Class] AND GLA[GENE] AND "human"[ORGN] AND "snp"[SNP_CLASS] - SNP Results.html' > dbSNP_snps_3.txt
$ perl three2one.pl dbSNP_snps_3.txt > dbSNP_snps.txt


In this database we searched for the gene GLA and downloaded the Table View table of the Allelic Variants (Allelic_variants.txt), which can be found in the Table of Contents. This table was parsed with the perl scripts readOMIM.pl and Omim2table.pl, which created all the output we needed for creation of the tables and statistics.

$ perl readOMIM.pl
$ perl Omim2table.pl > omim.wiki


Since there is no special site for the gene GLA, we performed a query with the search term "Gene=GLA". These dbSNP identifiers were downloaded and mapped onto a list of all informations on all identifiers (201) found, when searching for ""snp"[SNP_CLASS] AND GLA[GENE] AND "human"[ORGN]" in the dbSNP (Flat File display). This was done with the perl script parse_dbSNP.pl, which needed the input files snp_result.txt and rsnumber.txt. We realised that the amino acid position in this representation ignores the initial Methionine in the sequence, so we had to add 1 to the read aa positions.
A wiki table was created with SNPedia2table.pl.

$ perl parse_dbSNP.pl
$ perl SNPedia2table.pl > SNPedia.wiki


The textfile containing all informations gathered in SNPdbe (snps.txt) was downloaded after searching for the gene identifier "NP_000160" in the organism "human" (see). The textfile was parsed with the perl scripts readSNPdbe.pl andSNPdbe2table.pl and vizualised with the R script Hotspots_SNPdbe.R. For now, a SNP was considered disease causing if there was a disease listed, if it was a "N/A" it was assigned "non-disease". Later we added those SNPs that were also found in HGMD to the disease causing SNPs (see SNPdbe_manuallyCur.Rtable).

$ perl readSNPdbe.pl
$ perl SNPdbe2table.pl > SNPdbe.wiki
$ R CMD BATCH Hotspots_SNPdbe.R


First of all, we created the plots showing the distribution of SNPs along the sequence of the gene GLA with the R Script snp_distr.R. For this we prepared the data with map.pl. The non-redundant data was then used to build a histogram with Histogramm.R and to map the different groups of SNPs onto the structure 1R46 (Pymol script created with pymol_mark_positions.sh).

$ perl map.pl
$ R CMD BATCH snp_distr.R
$ R CMD BATCH Histogramm.R
$ pymol <(bash pymol_mark_positions.sh)

Afterwards we tried to vizualise disease and non-disease causing point mutations in one plot with Hotspots_all.R. We needed R tables of all databases for this, so some preparation had to be done with readHGMDforR.pl (input hgmd_snps.txt) and readdbSNPforR.pl (input dbSNP_snps.txt).

$ perl readHGMDforR.pl
$ perl readdbSNPforR.pl
$ R CMD BATCH Hotspots_all.R