Gaucher Disease: Task 07 - Research SNPs

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Revision as of 17:02, 24 June 2013 by Gerkej (talk | contribs) (HGMD)

HGMD

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.


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

blub

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

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 159142 protein sequences from 2985 organisms are covered in SNPdbe (2013-06-23).
  • 1691464 SAASs are referenced, consisting of:
    • natural variants
    • SAASs from mutagenesis experiments
    • sequencing conflicts
  • Human variants:
    • Overall: 967879 (100%)
    • Observed functional effect: 23121 (2%)
    • Disease associations: 26842 (3%)
    • Observed functional effect and disease: 1629 (0%)


In SNPdbe, look for disease causing mutations and those that have no effect (often not verified). Please disregard the two colums "Predicted functional effect" for this week. You can search for example your protein, gene or disease. Look at results for human. Is experimental evidence available? Use the conservation score as a first (simple) estimate of effect (disease causing) or no effect.

OMIM

Mutation map

Extract information for your protein/disease from the databases. Are there mutation hot-spots? Map approximately 100 point mutations onto your protein sequence (disease and non-disease causing).