Researching SNPs Gaucher Disease
HGMD
The Human Genome Mutation Database (HGMD)<ref name="hgmd">Stenson et al. 2009. The Human Gene Mutation Database (HGMD): 2008 Update. Genome Med</ref> is a collection of observed mutations in the human genome which are associated with various diseases. The mutations are taken from publications, both manually and automatically [1]. There is a public version with 88745 entries (9th June, 2012) and a professional version with 123565 entries. Since 2009, the public version has been extended only by few new entries such that it does no longer contain all currently known mutations [2]. The HGMD stores following types of mutations:
- Missense
- Mutations which result in another amino acid
- Nonsense
- Mutations which result in a stop codon
- Splicing
- Mutations which alter splice sites
- Regulatory
- Mutation which alter gene regulation
- Small/gross deletions
- Deletions which remove residues
- Small/gross insertions
- Insertion which give rise to new residues
- Small indels
- Insertion or deletion
- Duplications
- Duplication of gene fragments
- Complex rearrangements
- Gene fragments change their position
- Cepeat variations
- Varying number of sequence copies
<xr id="tab:hgmd_number"/> lists the number of mutations available in HGMD for the gene GBA which is causing Gaucher disease. A comprehensive list of all missense/nonsense mutations can be obtained by following the respective hyperlink.
<figtable id="tab:hgmd_number">
| Type | Count |
|---|---|
| Missense/nonsense | 250 |
| Splicing | 15 |
| Regulatory | 0 |
| Small deletions | 26 |
| Small insertions | 13 |
| Small indels | 2 |
| Gross deletions | 3 |
| Gross insertions/duplications | 1 |
| Complex rearrangements | 15 |
| Public total | 325 |
Number of mutations in HGMD for GBA. </figtable>
<xr id="tab:hgmd_missense"/> shows the wildtype version of P04062 with missense/nonsense mutations highlighted in red. Since the amino acid positions in HGMD already referred to P04062, no additional translation was required for creating <xr id="tab:hgmd_missense"/>.
<figtable id="tab:hgmd_missense">
1 11 21 31 41 51 61 71
Wildtype MEFSSPSREE CPKPLSRVSI MAGSLTGLLL LQAVSWASGA RPCIPKSFGY SSVVCVCNAT YCDSFDPPTF PALGTFSRYE
Missense MEFSSPSREE CPRPLSRVSI MAGSLTGLLL LQAVS!ASGA RPCIPKSFSY ISVLSVCNAT YCNSFDPPTF PALSTVSRYK
81 91 101 111 121 131 141 151
Wildtype STRSGRRMEL SMGPIQANHT GTGLLLTLQP EQKFQKVKGF GGAMTDAAAL NILALSPPAQ NLLLKSYFSE EGIGYNIIRV
Missense NIRSE!QMEL SMGPIQANHT GTGLPLTLQP E!!FQKANGF GGATTDAATL NILALSPPAQ NLLRKLCVSK EEIGYDISQA
161 171 181 191 201 211 221 231
Wildtype PMASCDFSIR TYTYADTPDD FQLHNFSLPE EDTKLKIPLI HRALQLAQRP VSLLASPWTS PTWLKTNGAV NGKGSLKGQP
Missense LVASCVFSIL TYP!EDTPHD FQLHNFSLPE ADTKLQILLS PQALQLA!CP V!PLDSS!PS LTRFKTKVEG NGKWPPEGQP
241 251 261 271 281 291 301 311
Wildtype GDIYHQTWAR YFVKFLDAYA EHKLQFWAVT AENEPSAGLL SGYPFQCLGF TPEHQRDFIA RDLGPTLANS THHNVRLLML
Missense EDICHQTRVR HCVKYLDACA EHKLQFWAVR A!NETPAVLL SVHHFQCQGL TPEQQ!DLTA HDLDATLANG THHNVRLPML
321 331 341 351 361 371 381 391
Wildtype DDQRLLLPHW AKVVLTDPEA AKYVHGIAVH WYLDFLAPAK ATLGETHRLF PNTMLFASEA CVGSKFWEQS VRLGSWDRGM
Missense DDQHLLPLHW AKVVLTDPEA AI!LHGIVVR RHLHFLDSAK AIPWKTHCLS PNTMPFASET YVGSKFGK!S LWLDF!D!GI
401 411 421 431 441 451 461 471
Wildtype QYSHSIITNL LYHVVGWTDW NLALNPEGGP NWVRNFVDSP IIVDITKDTF YKQPMFYHLG HFSKFIPEGS QRVGLVASQK
Missense QCRHGIIMKV LYHLVS!TA! KRDPNL!ERL IRLCTSFYSL FIVDITKHTI HQRRVVCHLD HFSEVIPEGS QGVGLVASQK
481 491 501 511 521 531
Wildtype NDLDAVALMH PDGSAVVVVL NRSSKDVPLT IKDPAVGFLE TISPGYSIHT YLWRRQ
Missense NDRDPVALMR PDGSPVVVMP KPSSKDVPLT IKYPAVSFPE TISPGYPTHI YLWRCR
GBA protein sequence P04062. Red: missense/nonsense mutations annotated in HGMD.
</figtable>
dbSNP
1 11 21 31 41 51 61 71
Wildtype MEFSSPSREE CPKPLSRVSI MAGSLTGLLL LQAVSWASGA RPCIPKSFGY SSVVCVCNAT YCDSFDPPTF PALGTFSRYE
Missense MEFSSPSREE CPRPSGGVSV MAGSLTGLLL LQAVSWASGA CPCIPESFGY SSVVCVCNAT YYESFDPRTF PALGTLSCYK
Synonymous MEFSSPSREE CPKPLSRVSI MAGSLTGLLL LQAVSWASGA RPCIPKSFGY SSVVCVCNAT YCDSFDPPTF PALGTFSRYE
81 91 101 111 121 131 141 151
Wildtype STRSGRRMEL SMGPIQANHT GTGLLLTLQP EQKFQKVKGF GGAMTDAAAL NILALSPPAQ NLLLKSYFSE EGIGYNIIRV
Missense SRSSGQWMEL STGPIQANYT GTGLLLTLQP EQKFQKVKGF GGAMTDAAAL NILALSPPAQ NLLLKSYFSE EGIGYKISWV
Synonymous STRSGRRMEL SMGPIQANHT GTGLLLTLQP EQKFQKVKGF GGAMTDAAAL NILALSPPAQ NLLLKSYFSE EGIGYNIIRV
161 171 181 191 201 211 221 231
Wildtype PMASCDFSIR TYTYADTPDD FQLHNFSLPE EDTKLKIPLI HRALQLAQRP VSLLASPWTS PTWLKTNGAV NGKGSLKGQP
Missense LIASCVFSIL TYIYEDTPHD FQLHNFSLPE EDTKLNILLN PRALQLAQRP ISLLASPWTS LTRLKTKVEE NGKESLKGQP
Synonymous PMASCDFSIR TYTYADTPDD FQLHNFSLPE EDTKLKIPLI HRALQLAQRP VSLLASPWTS PTWLKTNGAV NGKGSLKGQP
241 251 261 271 281 291 301 311
Wildtype GDIYHQTWAR YFVKFLDAYA EHKLQFWAVT AENEPSAGLL SGYPFQCLGF TPEHQRDFIA RDLGPTLANS THHNVRLLML
Missense EDICHQTWAR YLVKFLDAYA EHKLQFWAVR AENEPSAGLL NGYPFQCLGF TPEHQRDFIA HDLDRTLANG THHNVRLLML
Synonymous GDIYHQTWAR YFVKFLDAYA EHKLQFWAVT AENEPSAGLL SGYPFQCLGF TPEHQRDFIA RDLGPTLANS THHNVRLLML
321 331 341 351 361 371 381 391
Wildtype DDQRLLLPHW AKVVLTDPEA AKYVHGIAVH WYLDFLAPAK ATLGETHRLF PNTMLFASEA CVGSKFWEQS VRLGSWDRGM
Missense DDQHLLLPQW AKVVLTDPEA AICVYGIAVH WYLDFLDPAK ATLGETHHLF PNTMLFASEA CVGSKFWEQS VQLGSWDQGI
Synonymous DDQRLLLPHW AKVVLTDPEA AKYVHGIAVH WYLDFLAPAK ATLGETHRLF PNTMLFASEA CVGSKFWEQS VRLGSWDRGM
401 411 421 431 441 451 461 471
Wildtype QYSHSIITNL LYHVVGWTDW NLALNPEGGP NWVRNFVDSP IIVDITKDTF YKQPMFYHLG HFSKFIPEGS QRVGLVASQK
Missense QCSHRIIMNL LYHVVGCTAW NIALNPKGGL IWVRTSVESP TIVDITKETL YKQPILCHLG HFSKFIPEGS QRVGLVASPK
Synonymous QYSHSIITNL LYHVVGWTDW NLALNPEGGP NWVRNFVDSP IIVDITKDTF YKQPMFYHLG HFSKFIPEGS QRVGLVASQK
481 491 501 511 521 531
Wildtype NDLDAVALMH PDGSAVVVVL NRSSKDVPLT IKDPAVGFLE TISPGYSIHT YLWRRQ
Missense NNLDAVALMR PDGSAVVVVL NRSFKDVPPT IKEPAVGFLE TISPGYSIHI YLWCHQ
Synonymous NDLDAVALMH PDGSAVVVVL NRSSKDVPLT IKDPAVGFLE TISPGYSIHT YLWRRQ
