Mapping SNPs HEXA

Methods

First of all, we had to parse the HGMD database and the DB-SNP database.

HGMD

We logged us in and searched for Tay-Sachs diseases and chose one entry of HEXA. In our case there were two entries with identical content. We only looked at the missense/nonsense mutations, which are 68 annotated in HGMD. We just copied the webpage in a textfile and than wrote a short parser, which parse the codon change, amino acid change and codon number.

DBSNP

It was more complicated to parse the DBSNP output, than the output of HGMD. First of all, we search for HEXA in this database and chose only the SNPs which occur in human. We used the grapical output and again copied and pasted the page in a textfile. An entry in DBSNP has following structure: First of all there is the name of the SNP. Next the sequence and the graphical representation of the sequence. In the next line, there are the allel origin, the clinical relevance and last the annotations of the mutation. TBA...

Comparison of mutations in HGMD and SNP-DB

• Mutations annotated in both databases:

mutations which are not silent and cause a phenotype

Codonposition	Mutationposition	Amino Acids	Codons
26	3	Trp -> TER	TGGc -> TGA
39	2	Leu -> Arg	CTT -> CGT
127	1	Leu -> Phe	aCTC -> TTC
	2	Leu -> Arg	CTC -> CGC
137	1	Arg -> TER	cCGA -> TGA
170	1	Arg -> Trp	cCGG -> TGG
	2	Arg -> Gln	CGG -> CAG
178	2	Arg -> His	CGC -> CAC
	2	Arg -> Leu	CGC -> CTC
	1	Arg -> Cys	tCGC -> TGC
180	3	Tyr -> TER	TACc -> TAG
	1	Tyr -> His	tTAC -> CAC
197	2	Lys -> Thr	AAA -> ACA
200	1	Val -> Met	cGTG -> ATG
204	2	His -> Arg	CAT -> CGT
210	2	Ser -> Phe	TCC -> TTC
211	2	Phe -> Ser	TTC -> TCC
247	1	Arg -> Trp	aCGG -> TGG
250	1	Gly -> Ser	gGGT -> AGT
	2	Gly -> Asp	GGT -> GAT
	2	Gly -> Val	GGT -> GTT
258	1	Asp -> His	tGAC -> CAC
269	1	Gly -> Ser	aGGT -> AGT
	2	Gly -> Asp	GGT -> GAT
301	2	Met -> Arg	ATG -> AGG
329	2	Trp -> TER	TGG -> TAG
393	1	Arg -> TER	gCGA -> TGA
420	3	Trp -> Cys	TGGt -> TGC
	3	Trp -> Cys	TGGt -> TGT
451	1	Leu -> Val	tCTG -> GTG
454	2	Gly -> Asp	GGT -> GAT
	1	Gly -> Ser	tGGT -> AGT
474	3	Trp -> Cys	TGGc -> TGC
482	1	Glu -> Lys	cGAA -> AAA
485	1	Trp -> Arg	gTGG -> CGG
499	1	Arg -> Cys	aCGT -> TGT
	2	Arg -> His	CGT -> CAT
504	1	Arg -> Cys	cCGC -> TGC
	2	Arg -> His	CGC -> CAC

Graphical representation:

 MTSSRLWFSLLLAAAFAGRATALWPWPQNFQTSDQRYVLYPNNFQFQYDVSSAAQPGCSVLD
 MTSSRLWFSLLLAAAFAGRATALWP!PQNFQTSDQRYVRYPNNFQFQYDVSSAAQPGCSVLD
 
 
 EAFQRYRDLLFGSGSWPRPYLTGKRHTLEKNVLVVSVVTPGCNQLPTLESVENYTLTINDD
 EAFQRYRDLLFGSGSWPRPYLTGKRHTLEKNVLVVSVVTPGCNQLPTLESVENYTLTINDD
 
 
 QCLLLSETVWGALRGLETFSQLVWKSAEGTFFINKTEIEDFPRFPHRGLLLDTSRHYLPLS
 QCLFLSETVWGAL!GLETFSQLVWKSAEGTFFINKTEIEDFPRFPHWGLLLDTSHH!LPLS
 
 
 SILDTLDVMAYNKLNVFHWHLVDDPSFPYESFTFPELMRKGSYNPVTHIYTAQDVKEVIEY
 SILDTLDVMAYNTLNMFHWRLVDDPFSPYESFTFPELMRKGSYNPVTHIYTAQDVKEVIEY
 
 
 ARLRGIRVLAEFDTPGHTLSWGPGIPGLLTPCYSGSEPSGTFGPVNPSLNNTYEFMSTFFL
 AWLRSIRVLAEFHTPGHTLSWGPSIPGLLTPCYSGSEPSGTFGPVNPSLNNTYEFRSTFFL
 
 
 EVSSVFPDFYLHLGGDEVDFTCWKSNPEIQDFMRKKGFGEDFKQLESFYIQTLLDIVSSYG
 EVSSVFPDFYLHLGGDEVDFTC!KSNPEIQDFMRKKGFGEDFKQLESFYIQTLLDIVSSYG
 
 
 KGYVVWQEVFDNKVKIQPDTIIQVWREDIPVNYMKELELVTKAGFRALLSAPWYLNRISYG
 KGYVVWQEVFDNKVKIQPDTIIQVW!EDIPVNYMKELELVTKAGFRALLSAPCYLNRISYG
 
 
 PDWKDFYIVEPLAFEGTPEQKALVIGGEACMWGEYVDNTNLVPRLWPRAGAVAERLWSNKL
 PDWKDFYIVEPLAFEGTPEQKAVVIDGEACMWGEYVDNTNLVPRLCPRAGAVAKRLRSNKL
 
 
 TSDLTFAYERLSHFRCELLRRGVQAQPLNVGFCEQEFEQT
 TSDLTFAYECLSHFCCELLRRGVQAQPLNVGFCEQEFEQT


 Non-silent mutation       Silent mutation       Wrong AA in mutation annotation

~

The non-silent mutations are colored in red. A "!" in the sequence means that there is a stop codon.
If there are more than one mutation at one position, we always used the first mutation in the graphical representation.

Mutations annotated only in HGMD: not found

Mutations annotated only in SNP-DB:

mutations annotated only in SNP-DB and not silent (pos in codon ist annotiert und sicher):

Codonposition	Mutationposition	Amino Acids	Codons
293	2	Ser -> Ile	AGT -> ATT
399	1	Asn -> Asp	AAC -> GAC
436	1	Ile -> Val	ATA -> GTA
456	2	Tyr -> Ser	TAT -> TCT
506	3	Glu -> Asp	GAA -> GAC
		Glu -> Asp	GAA -> GAT

Graphical representation:

 MTSSRLWFSLLLAAAFAGRATALWPWPQNFQTSDQRYVLYPNNFQFQYDVSSAAQPGCSVLD
 MTSSRLWFSLLLAAAFAGRATALWPWPQNFQTSDQRYVLYPNNFQFQYDVSSAAQPGCSVLD
 
 
 EAFQRYRDLLFGSGSWPRPYLTGKRHTLEKNVLVVSVVTPGCNQLPTLESVENYTLTINDD
 EAFQRYRDLLFGSGSWPRPYLTGKRHTLEKNVLVVSVVTPGCNQLPTLESVENYTLTINDD
 
 
 QCLLLSETVWGALRGLETFSQLVWKSAEGTFFINKTEIEDFPRFPHRGLLLDTSRHYLPLS
 QCLLLSETVWGALRGLETFSQLVWKSAEGTFFINKTEIEDFPRFPHRGLLLDTSRHYLPLS
 
 
 SILDTLDVMAYNKLNVFHWHLVDDPSFPYESFTFPELMRKGSYNPVTHIYTAQDVKEVIEY
 SILDTLDVMAYNKLNVFHWHLVDDPSFPYESFTFPELMRKGSYNPVTHIYTAQDVKEVIEY
 
 
 ARLRGIRVLAEFDTPGHTLSWGPGIPGLLTPCYSGSEPSGTFGPVNPSLNNTYEFMSTFFL
 ARLRGIRVLAEFDTPGHTLSWGPGIPGLLTPCYSGSEPSGTFGPVNPILNNTYEFMSTFFL
 
 
 EVSSVFPDFYLHLGGDEVDFTCWKSNPEIQDFMRKKGFGEDFKQLESFYIQTLLDIVSSYG
 EVSSVFPDFYLHLGGDEVDFTCWKSNPEIQDFMRKKGFGEDFKQLESFYIQTLLDIVSSYG
 
 
 KGYVVWQEVFDNKVKIQPDTIIQVWREDIPVNYMKELELVTKAGFRALLSAPWYLNRISYG
 KGYVVWQEVFDNKVKIQPDTIIQVWREDIPVDYMKELELVTKAGFRALLSAPWYLNRISYG
 
 
 PDWKDFYIVEPLAFEGTPEQKALVIGGEACMWGEYVDNTNLVPRLWPRAGAVAERLWSNKL
 PDWKDFYVVEPLAFEGTPEQKALVIGGSACMWGEYVDNTNLVPRLWPRAGAVAERLWSNKL
 
 
 TSDLTFAYERLSHFRCELLRRGVQAQPLNVGFCEQEFEQT
 TSDLTFAYERLSHFRCDLLRRGVQAQPLNVGFCEQEFEQT


 Non-silent mutation       Silent mutation       Wrong AA in mutation annotation

mutations annotated only in SNP-DB and silent: (pos in codon ist annotiert und sicher)

Position	Amino Acids	Codons
506	Glu -> Glu	GAA -> GAG

Graphical representation:

 MTSSRLWFSLLLAAAFAGRATALWPWPQNFQTSDQRYVLYPNNFQFQYDVSSAAQPGCSVLD
 MTSSRLWFSLLLAAAFAGRATALWPWPQNFQTSDQRYVLYPNNFQFQYDVSSAAQPGCSVLD
 
 
 EAFQRYRDLLFGSGSWPRPYLTGKRHTLEKNVLVVSVVTPGCNQLPTLESVENYTLTINDD
 EAFQRYRDLLFGSGSWPRPYLTGKRHTLEKNVLVVSVVTPGCNQLPTLESVENYTLTINDD
 
 
 QCLLLSETVWGALRGLETFSQLVWKSAEGTFFINKTEIEDFPRFPHRGLLLDTSRHYLPLS
 QCLLLSETVWGALRGLETFSQLVWKSAEGTFFINKTEIEDFPRFPHRGLLLDTSRHYLPLS
 
 
 SILDTLDVMAYNKLNVFHWHLVDDPSFPYESFTFPELMRKGSYNPVTHIYTAQDVKEVIEY
 SILDTLDVMAYNKLNVFHWHLVDDPSFPYESFTFPELMRKGSYNPVTHIYTAQDVKEVIEY
 
 
 ARLRGIRVLAEFDTPGHTLSWGPGIPGLLTPCYSGSEPSGTFGPVNPSLNNTYEFMSTFFL
 ARLRGIRVLAEFDTPGHTLSWGPGIPGLLTPCYSGSEPSGTFGPVNPSLNNTYEFMSTFFL
 
 
 EVSSVFPDFYLHLGGDEVDFTCWKSNPEIQDFMRKKGFGEDFKQLESFYIQTLLDIVSSYG
 EVSSVFPDFYLHLGGDEVDFTCWKSNPEIQDFMRKKGFGEDFKQLESFYIQTLLDIVSSYG
 
 
 KGYVVWQEVFDNKVKIQPDTIIQVWREDIPVNYMKELELVTKAGFRALLSAPWYLNRISYG
 KGYVVWQEVFDNKVKIQPDTIIQVWREDIPVNYMKELELVTKAGFRALLSAPWYLNRISYG
 
 
 PDWKDFYIVEPLAFEGTPEQKALVIGGEACMWGEYVDNTNLVPRLWPRAGAVAERLWSNKL
 PDWKDFYIVEPLAFEGTPEQKALVIGGEACMWGEYVDNTNLVPRLWPRAGAVAERLWSNKL
 
 
 TSDLTFAYERLSHFRCELLRRGVQAQPLNVGFCEQEFEQT
 TSDLTFAYERLSHFRCELLRRGVQAQPLNVGFCEQEFEQT


 Non-silent mutation       Silent mutation        Wrong AA in mutation annotation

silent mutation (unklar an welcher stelle im codon wird nirgends annotiert):

This mutations are badly annotated in the SNP-DB. Therefore we rotated the found codons, because the original codon has to code for the amino acid which occur in the protein sequence. Therefore we used the codon with the mutation at position one, position two and position three. Next we also reverse it and made the complemetary sequence of both. The detailed result can be seen [here]

Here is the result, which combinations are possible:

Codonposition	Mutationposition	Amino Acids	Codons
3	1	Phe -> Leu	TTC -> CTC
	2	Val -> Ala	GTT -> GCT
	3	Ser -> Ser	AGT -> AGC
29	1	Phe -> Leu	TTC -> CTC
	2	Val -> Ala	GTT -> GCT
	3	Cys -> Cys	TGT -> TGC
109	1	Phe -> Leu	TTT -> CTT
	2	Leu -> Pro	CTT -> CCT
	3	Thr -> Thr	ACT -> ACC
179	1	Val -> Leu	GTA -> CTA
	2	Ser -> Thr	AGT -> ACT
	3	Asp -> Asp	GAG -> GAC
203	1	STOP -> Arg	TGA -> CGA
	2	Leu -> Pro	CTG -> CCG
	3	Thr -> Thr	ACT -> ACC
208	1	Leu -> Leu	TTG -> CTG
	2	Ile -> Thr	ATT -> ACT
	3	Tyr -> Tyr	TAT -> TAC
248	1	Asp -> Lys	GAA -> AAA
	2	Arg -> Glu	CGA -> CAA
	3	Pro -> Pro	CCG -> CCA
324	1	TER -> Arg	TGA -> AGA
		TER -> Arg	TGA -> CGA
	2	Leu -> TER	TTG -> TAG
		Leu -> Ser	TTG -> TCG
	3	Val -> Val	GTT -> GTA
		Val -> Val	GTT -> GTC
446	1	Gly -> Arg	GGG -> AGG
	2	Arg -> Glu	CGG -> CAG
	3	Ser -> Ser	TCG -> TCA
476	1	Val -> Ile	GTT -> ATT
	2	Ser -> Asn	AGT -> AAT
	3	Lys -> Lys	AAG -> AAA
540	1	STOP -> Glu	TAG -> CAG
	2	Ile -> Thr	ATA -> ACA
	3	His -> His	CAT -> CAC

Graphical representation:

 MTSSRLWFSLLLAAAFAGRATALWPWPQNFQTSDQRYVLYPNNFQFQYDVSSAAQPGCSVLD
 MTSSRLWFSLLLAAAFAGRATALWPWPQXFQTSDQRYVLYPNNFQFQYDVSSAAQPGCSVLD
 
 
 EAFQRYRDLLFGSGSWPRPYLTGKRHTLEKNVLVVSVVTPGCNQLPTLESVENYTLTINDD
 EAFQRYRDLLFGSGSWPRPYLTGKRHTLEKNVLVVSVVTPGCNQLPTLESVENYTLTINDD
 
 
 QCLLLSETVWGALRGLETFSQLVWKSAEGTFFINKTEIEDFPRFPHRGLLLDTSRHYLPLS
 QCLLLSETVWGALRGLETFSQLVWKSAEGTFFINKTEIEDFPRFPHRGLLLDTSRXYLPLS
 
 
 SILDTLDVMAYNKLNVFHWHLVDDPSFPYESFTFPELMRKGSYNPVTHIYTAQDVKEVIEY
 SILDTLDVMAYNKLNVFHXHLVDXPSFPYESFTFPELMRKGSYNPVTHIYTAQDVKEVIEY
 
 
 ARLRGIRVLAEFDTPGHTLSWGPGIPGLLTPCYSGSEPSGTFGPVNPSLNNTYEFMSTFFL
 ARXRGIRVLAEFDTPGHTLSWGPGIPGLLTPCYSGSEPSGTFGPVNPSLNNTYEFMSTFFL
 
 
 EVSSVFPDFYLHLGGDEVDFTCWKSNPEIQDFMRKKGFGEDFKQLESFYIQTLLDIVSSYG
 EVSSVFPDFYLHLGGDEVDFTCWKSNPEIQDFMRKKGFGEDFKQLESFYIQTLLDIVSSYG
 
 
 KGYVVWQEVFDNKVKIQPDTIIQVWREDIPVNYMKELELVTKAGFRALLSAPWYLNRISYG
 KGYVVWQEVFDNKVKIQPDTIIQVWREDIPVNYMKELELVTKAGFRALLSAPWYLNRISYG
 
 
 PDWKDFYIVEPLAFEGTPEQKALVIGGEACMWGEYVDNTNLVPRLWPRAGAVAERLWSNKL
 PDWKDFYIVEPLAFEGTXEQKALVIGGEACMWGEYVDNTNLVPRLWPXAGAVAERLWSNKL
 
 
 TSDLTFAYERLSHFRCELLRRGVQAQPLNVGFCEQEFEQT
 TSDLTFAYERLSHFRCELLRRGVQAQPLNVGFCEQEFEQT


 Non-silent mutation       Silent mutation        Wrong AA in mutation annotation