Fabry:Mapping point mutations

Fabry Disease » Mapping point mutations

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The following analyses were performed on the basis of the α-Galactosidase A sequence. Please consult the journal for the commands used to generate the results.

HGMD

Mutation types:

• Missense/nonsense
• Splicing
• Regulatory
• Small deletions
• Small insertions
• Small indels
• Gross deletions
• Gross insertions
• Complex
• Repeats

Missense/nonsense mutations

dbSNP

At the time we checked dbSNP, it listed eight silent single point mutations.

OMIM

<figure id="fig:OMIM_SNPs">

Distribution and number of SNPs along the sequence of GLA

</figure>

The OMIM database lists 62 (actually 63, since one entry contains 2 SNPs) allelic variants for the gene GLA. Of these, 6 are exon deletions, 10 are base pair deletions, 4 are located in non-coding regions, 1 was an exon duplication and 2 Insertions (see OMIM data-Allelic variants). The remaining 40 variants are specified as SNPs and are listed in OMIM data-SNPs.
Of course, all of the mentioned mutations are disease causing. In <xr id="fig:OMIM_SNPs"/> we show the distribution of SNPs along the sequence of the α-galactosidase A coding gene. There seems to be no real "hotspot" of SNPs, but a long strip of sequence without any point mutation (position 66-112). In the signal peptide only one mutation is listed, and in at the active site amino acids (170 and 231), as well as the binding site (203-207) there are none.

SNPedia

<figure id="fig:SNPedia_SNPs">

Distribution and number of SNPs found in SNPedia along the sequence of GLA

</figure>

In SNPedia exists a site for the disease, that is caused by mutations in the gene we are examining, Fabry Disease, but not for the gene itself (GLA). Thus we performed a query with the search term "Gene=GLA", which resulted in 40 hits (see SNPedia_data). 32 are missense mutations and the remaining 8 are stop-gained.
Again, only one hit was in the signal peptide part of the sequence and none of the important residues is mutated (see <xr id="fig:SNPedia_SNPs"/>). The gap of no variation between position 66 and 112 can be observed as well and besides from that a rather even distribution without big peaks.
Without deeper look, it can be said, that the results from OMIM and SNPedia are very similar, by simply comparing <xr id="fig:SNPedia_SNPs"/> and <xr id="fig:OMIM_SNPs"/>

SNPdbe

<figure id="fig:SNPdbe_SNPs">

Distribution and number of SNPs found in SNPdbe along the sequence of GLA. Disease causing mutations are red, non-disease causing green

</figure>

A search in the SNPdbe database revealed 57 mutations (source), which are listed in SNPdbe data Different from most other databases, SNPdbe lists desease causing and non-disease causing mutations.