Gaucher Disease: Task 07 - Research SNPs
HGMD
HGMD professional was last updated in March 2013. The free public HGMD version provides data from the release of HGMD proffessional in 2008. The database contains the first example of disease causing or disease associated mutations as well as disease-associated/functional polymorphisms. The informations are taken from literature or reported functional studies. Only non-silent mutations in the coding region are considered. Each mutation is stored once in the database. Additional to the infomation shown in the second table below, the information about a mutation includes its associated disease phenotype, chromosomal location, mutation type, gene symbol and the reference of its first literature report. HGMD professional also provides a mutation viewer. The database has access to more than 250 Journals, that are searched by a combination of computerised and manual procedures to find new detected mutations in published articles about germline mutations causing human genetic diseases.
The Glucocerebrosidase has the gene symbol GBA. A research on The Human Gene Mutation Database for GBA leads to the following results:
GBA in HGMD | |||
---|---|---|---|
Mutation Type | Number of Mutations | Effect of Mutation | |
Missense/nonsense | 256 | substitutions of a single base-pair in coding regions, that cause a amino acid or stop/start codon change | |
Splicing | 16 | mutations that influence the mRNA splicing | |
Regulatory | 0 | different Regulation caused by substitution | |
Small deletions | 26 | micro-deletions (< 21 bp) | |
Small insertions | 13 | micro-insertions (<21 bp) | |
Small indels | 4 | micro-indels (<21 bp) | |
Gross deletions | 3 | deletion (>20 bp) | |
Gross insertions/duplications | 1 | insertion (>20 bp) | |
Complex rearrangements | 16 | rearangement of DNA fragments within the sequence | |
Repeat variations | 0 | different number of repeats |
GBA is not affected by a regulatory mutations and repeated variations. The mutations on GBA do not only result to Gaucher's disease or influence its phenotype, but may also have an effect on the phenotype of the diseases Parkinson and Alzheimer.
HGMD public (2008 update) provides 335 mutations for GBA. On HGMD Professional 2013.1, 380 mutations can be found.
The following table of Missense/nonsense mutations on GBA shows an abridgement of 10 mutations out of all 256 known mutation of the public version of HGMD. The high naumber of mutations show the high liability of GBA on Gaucher causing mutations. Some position specific amino acids have a higher liability to this disease, as more than one mutation on that position can cause a Missense/nonsense mutations, that leads to Gaucher's disease.
Missense/nonsense mutations on GBA | |||
---|---|---|---|
Accession Number | Codon change | Amino acid change | Codon Number |
CM081634 | cGGC-AGC | Gly-Ser | 49 |
CM057078 | AGC-ATC | Ser-Ile | 51 |
CM044630 | gGTG-ATG | Val-Met | 54 |
CM960691 | gGTG-CTG | Val-Leu | 54 |
HM971738 | TGT-TCT | Cys-Ser | 55 |
CM081630 | AGT-AAT | Ser-Asn | 81 |
CM950560 | ACA-ATA | Thr-Ile | 82 |
CM960692 | GGG-GAG | Gly-Glu | 85 |
CM016030 | gCGA-TGA | Arg-Term | 86 |
CM950561 | aCGG-TGG | Arg-Trp | 87 |
dbSNP
The available data in dbSNP (version 138) were released on April 25, 2013. It provides mutation information for the three organisms, Homo Sapiens, Mus Musculus and Bos Taurus. The Database contains single base nucleotide subsitutions as well as short deletion and insertion polymorphisms. On GBA 59 silent mutations were found in dbSNP.
>gnl|dbSNP|rs141710041 rs=141710041|pos=51|len=101|taxid=9606|mol="genomic"|class=snp|alleles="A/G"|build=134|allele origin=G(somatic)/A(germline)|suspect=?|clinsig=other GTCTCCAGGA AGCCCACAGC AGGATCCTTG ATGGTAAGAG GCACATCCTT R GAGGAGCTAG GGAGCAGGGA GGAGAAGCTG AGAGTGTGAT CCTGCCAAGG
In dbSNP, look for silent (point) mutations. In most cases, significantly more than 100 mutations are known. The residue numbers in the databases may not correspond to each other.
SNPedia
5 SNPs were found
SNPdbe
- The following information (if available) is given on each SAAS (single amino acid substitution):
- Experimentally derived functional and structural impact
- Predicted functional effect
- Associated disease
- Average heterozygosity
- Experimental evidence of the nsSNP
- Evolutionary conservation of wildtype and mutant amino acid
- Link-outs to external databases
- Last update: 2012-02-20 (updated to recent Swiss-Prot release (2012-01)).
- The information comes from various databases (SwissProt, PMD, dbSNP, 1000 Genomes)
- Currently (2013-06-23) 159142 protein sequences from 2985 organisms are covered in SNPdbe and 1691464 SAASs are referenced, consisting of natural variants, SAASs from mutagenesis experiments and sequencing conflicts
- Human variants:
- Overall: 967879 (100%)
- Observed functional effect: 23121 (2%)
- Disease associations: 26842 (3%)
- Observed functional effect and disease: 1629 (0%)
Search for gene GBA in human delivered 638 entries.
effect no effect experimental evidence