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== First impression == ==Protocol== Further information can be found in the [[CD_task5_protocol|protocol]]. == First impression == ===HGMD=== 74 (79 in 2012 professional) total for cDNA sequence NM_000049.2 and amino acid sequence NP_000040.1, out of which * 47 missense/nonsense * 5 splicing * 12 small deletions * 2 small insertions * 1 indel * 7 gross deletions [http://www.hgmd.cf.ac.uk/ac/gene.php?gene=ASPA link to search] === SNPdbe === * 55 total * 29 labelled as involved in Canavan Disease * 12 with experimental evidence * predicted effect for each variant (SIFT, Snap) [http://www.rostlab.org/services/snpdbe/dosearch.php?id=name&val=aspa&organism2=human&organism1= link to search] === dbSNP === * same identifiers for sequence as HGMD * "synonymous-codon"[Function_Class] AND ASPA[GENE] AND "human"[ORGN] AND "snp"[SNP_CLASS] yields only 9 results * 505 results for SNPs in general in human ** 458 for NP_000040.1 (coding: 23) ** 493 for NP_001121557.1 (coding: 23) [http://www.ncbi.nlm.nih.gov/projects/SNP/snp_ref.cgi?showRare=on&chooseRs=coding&locusId=443&mrna=NM_001128085.1&ctg=NT_010718.16&prot=NP_001121557.1&orien=forward&refresh=refresh= link to search] ===SNPedia === links to other pages === OMIM === *12 allelic variants listed for Aspartoacylase => all linked to Canavan Disease [http://omim.org/allelicVariant/608034 link to ASPA variants] == Coding SNPs == <table align="right"> <tr> <td> <figure id="venny">[[File:overlap_venny.png|thumb|200px|<b><xr nolink id="venny"/></b><br> Overlap of contained SNPs between the databases.]]</figure></td> </tr> </table> From the above mentioned SNP databases we extracted all coding SNPs for Aspartoacylase. The venn diagram in <xr id="venny"/> shows the overlap of the contained SNPs in the three biggest database sources. We used the sequence position of the listed SNPs as an identifier to create a unique list of known SNPs. <xr id="coding_snp_table"/> shows the resulting list of unique SNPs. For each polymorphism, the source is given (i.e., from which DB the SNP was extracted), as well as annotated validation, if available. The resulting table contains 78 SNPs in total, out of which 48 are reported to cause the Canavan Disease. <figtable id="coding_snp_table"> <table cellspacing=0 align="center" cellpadding=5> <caption align="center"><b><xr nolink id="coding_snp_table"/></b> In this table all SNPs for Aspartoacylase are listed that could be found in HGMD, dbSNPs, SNPdbe and OMIM. Mutations in red are reported to cause the Canavan Disease.</caption> <tr> <td style="border-bottom:solid;border-right:solid;"><b>Residue Position</b></td> <td style="border-bottom:solid;border-right:solid;"><b>Identifier</b></td> <td style="border-bottom:solid;border-right:solid;"><b>Reference DB</b></td> <td style="border-bottom:solid;border-right:solid;"><b>Validation evidence</b></td> <td style="border-bottom:solid;border-right:solid;"><b>SNP Type</b></td> <td style="border-bottom:solid;border-right:solid;"><b>Mutation</b></td> </tr> <tr bgcolor="#C1FFC1"> <td style="border-right:solid" align="left">4</td> <td style="border-right:solid" align="left">rs142041344 </td> <td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td> <td style="border-right:solid" align="left">1000Genomes </td> <td style="border-right:solid" align="left">missense</td> <td style="border-right:solid" align="left">C4R</td> </tr> <tr bgcolor="#BFEFFF"> <td style="border-right:solid" align="left" >14</td> <td style="border-right:solid" align="left">CM063852</td> <td style="border-right:solid" align="left">HGMD</td> <td style="border-right:solid" align="left">Zeng (2006) Mol Genet Metab 89</td> <td style="border-right:solid" align="left">missense</td> <td style="color:red;border-right:solid;border-color:black" align="left">V14G</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >16</td><td style="border-right:solid" align="left"><br> CM960084</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left">Kaul (1996) Am J Hum Genet 59</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">I16T</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >18</td><td style="border-right:solid" align="left">CM067343</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Zeng (2006) Adv Exp Med Biol 576</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">G18R</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >21</td><td style="border-right:solid" align="left">CM001608</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left">SHGMD857217istermans (2000) Eur J Hum Genet 8</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">H21P</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >24</td><td style="border-right:solid" align="left">rs104894551 <br> CM023602</td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe<br> OMIM<br> HGMD</td><td style="border-right:solid" align="left"> Multiple independent submissions to the refSNP cluster<br> Zeng (2002) J Inherit Metab Dis 25</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">E24G</td> </tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >26</td><td style="border-right:solid" align="left">rs145616193 </td><td style="border-right:solid" align="left">dbSNP</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">synonymous</td><td style="border-right:solid" align="left">T26T</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >27</td><td style="border-right:solid" align="left">CM960085</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left"> Kaul (1996) Am J Hum Genet 59</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">G27R</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >33</td><td style="border-right:solid" align="left">rs138158568 </td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">H33R</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >53</td><td style="border-right:solid" align="left">rs17850703 </td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">T53A</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >57</td><td style="border-right:solid" align="left">CM001609</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left">Sistermans (2000) Eur J Hum Genet 8</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">A57T</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >68</td><td style="border-right:solid" align="left"> CM023603</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left">Zeng (2002) J Inherit Metab Dis 25</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">D68A</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >71</td><td style="border-right:solid" align="left">rs104894553 <br> CM060201</td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe<br> HGMD</td><td style="border-right:solid" align="left">multiple independent submissions to the refSNP cluster<br>Janson (2006) Ann Neurol 59</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">R71H</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >71_2</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">R71K</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >82</td><td style="border-right:solid" align="left">rs80099330 </td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left">Multiple independent submissions to the refSNP cluster<br>Validated by frequency or genotype data<br>1000 Genome project</td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">M82T</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >93</td><td style="border-right:solid" align="left">rs144639820 </td><td style="border-right:solid" align="left">dbSNP</td><td style="border-right:solid" align="left">Validated by frequency or genotype data</td><td style="border-right:solid" align="left">synonymous</td><td style="border-right:solid" align="left">A93A</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >109</td><td style="border-right:solid" align="left">CM990192</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Elpeleg (1999) J Inherit Metab Dis 22</td><td style="border-right:solid" align="left">nonsense</td><td style="color:red;border-right:solid;border-color:black" align="left">Y109Ter</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >111</td><td style="border-right:solid" align="left">rs181347986 </td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left"> 1000 Genome project</td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">I111V</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >114</td><td style="border-right:solid" align="left">CM023014</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left">Olsen (2002) J Med Genet 39</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">D114Y</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >114_2</td><td style="border-right:solid" align="left">CM960086</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Kaul (1996) Am J Hum Genet 59</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">D114E</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >121</td><td style="border-right:solid" align="left">rs148451498 </td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">N121D</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >121_2</td><td style="border-right:solid" align="left">CM063846</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Zeng (2006) Mol Genet Metab 89</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">N121I</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >123</td><td style="border-right:solid" align="left">CM960087</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left"> Kaul (1996) Am J Hum Genet 59</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">G123E</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >143</td><td style="border-right:solid" align="left">rs199565861</td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left"> 1000 Genome project</td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">I143V</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >143_2</td><td style="border-right:solid" align="left">CM063849</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Zeng (2006) Mol Genet Metab 89</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">I143F</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >143_3</td><td style="border-right:solid" align="left">CM980125</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Kobayashi (1998) Hum Mutat S1, S308</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">I143T</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >152</td><td style="border-right:solid" align="left">rs104894548 <br> CM950102</td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe<br> OMIM<br> HGMD</td><td style="border-right:solid" align="left"> Multiple independent submissions to the refSNP cluster<br>Kaul (1995) Hum Mutat 5</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">C152R</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >152_2</td><td style="border-right:solid" align="left">CM023604</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Zeng (2002) J Inherit Metab Dis 25</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">C152W</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >152_3</td><td style="border-right:solid" align="left">CM960088</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Kaul (1996) Am J Hum Genet 59, 95</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">C152Y</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >153</td><td style="border-right:solid" align="left">rs141755746 </td><td style="border-right:solid" align="left">dbSNP</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">synonymous</td><td style="border-right:solid" align="left">Y153Y</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >154</td><td style="border-right:solid" align="left">rs147193431 <br> rs2228435</td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">V154I</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >157</td><td style="border-right:solid" align="left">rs140357187 </td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">I157T</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >164</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">Y164F</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >166</td><td style="border-right:solid" align="left">CM063847</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Zeng (2006) Mol Genet Metab 89</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">T166I</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >168</td><td style="border-right:solid" align="left"> CM001610</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left">Sistermans (2000) Eur J Hum Genet 8</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">R168H</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >168_2</td><td style="border-right:solid" align="left">CM960089</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Kaul (1996) Am J Hum Genet 59</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">R168C</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >170</td><td style="border-right:solid" align="left">rs144321760 </td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left">Validated by frequency or genotype data<br> by freq</td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">I170T</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >178</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">E178A</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >181_2</td><td style="border-right:solid" align="left">CM063850</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Zeng (2006) Mol Genet Metab 89</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">P181L</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >181</td><td style="border-right:solid" align="left">CM001611</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left">Sistermans (2000) Eur J Hum Genet 8</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">P181T</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >183</td><td style="border-right:solid" align="left">CM990193</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left"> Elpeleg (1999) J Inherit Metab Dis 22</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">P183H</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >184</td><td style="border-right:solid" align="left">CM023605</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Zeng (2002) J Inherit Metab Dis 25</td><td style="border-right:solid" align="left">nonsense</td><td style="color:red;border-right:solid;border-color:black" align="left">Q184Ter</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >186</td><td style="border-right:solid" align="left">CM990194</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left">Elpeleg (1999) J Inherit Metab Dis 22</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">V186F</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >195</td><td style="border-right:solid" align="left">CM990195</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left">Elpeleg (1999) J Inherit Metab Dis 22</td><td style="border-right:solid" align="left">missense</td> <td style="color:red;border-right:solid;border-color:black" align="left">M195R</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >202</td><td style="border-right:solid" align="left">rs147763700 </td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">A202S</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >213</td><td style="border-right:solid" align="left">CM055097</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Tacke (2005) Neuropediatrics 36</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">K213E</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >214</td><td style="border-right:solid" align="left">CM023606</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Zeng (2002) J Inherit Metab Dis 25</td><td style="border-right:solid" align="left">nonsense</td><td style="color:red;border-right:solid;border-color:black" align="left">E214Ter</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >218</td><td style="border-right:solid" align="left">rs104894549<br>CM950103 </td><td style="border-right:solid" align="left">dbSNP<br>HGMD</td><td style="border-right:solid" align="left"> Multiple independent submissions to the refSNP cluster<br>Shaag (1995) Am J Hum Genet 57</td><td style="border-right:solid" align="left">nonsense</td><td style="color:red;border-right:solid;border-color:black" align="left">C218Ter</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >220</td><td style="border-right:solid" align="left">rs139053885 </td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">I220T</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >226_2</td><td style="border-right:solid" align="left">CM086530</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Di Pietro (2008) Clin Biochem 41</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">I226T</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >226</td><td style="border-right:solid" align="left">rs201887670</td><td style="border-right:solid" align="left">dbSNP</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">I226K</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >231</td><td style="border-right:solid" align="left">rs104894550 <br> CM994594</td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe<br> OMIM<br> HGMD</td><td style="border-right:solid" align="left"> Multiple independent submissions to the refSNP cluster<br>Rady (1999) Am J Med Genet 87</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">Y231C</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >231_2</td><td style="border-right:solid" align="left">CM940123</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Kaul (1994) Am J Hum Genet 55</td><td style="border-right:solid" align="left">nonsense</td><td style="color:red;border-right:solid;border-color:black" align="left">Y231Ter</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >235</td><td style="border-right:solid" align="left">rs149842031 </td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left">Multiple independent submissions to the refSNP cluster <br> Validated by frequency or genotype data <br>1000 Genome project</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">E235K</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >236</td><td style="border-right:solid" align="left">rs149189911 </td><td style="border-right:solid" align="left">dbSNP</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">synonymous</td><td style="border-right:solid" align="left">N236N</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >239</td><td style="border-right:solid" align="left">rs145085349 </td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">I239T</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >244</td><td style="border-right:solid" align="left">CM023607</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left">Zeng (2002) J Inherit Metab Dis 25</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">H244R</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >244_2</td><td style="border-right:solid" align="left">CM063848</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Zeng (2006) Mol Genet Metab 89</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">H244L</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >249</td><td style="border-right:solid" align="left">rs104894552 <br> CM023015</td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe<br> HGMD</td><td style="border-right:solid" align="left"> Multiple independent submissions to the refSNP cluster<br>Olsen (2002) J Med Genet 39</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">D249V</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >270</td><td style="border-right:solid" align="left">rs200126822</td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left">1000 Genome project </td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">I270T</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >272</td><td style="border-right:solid" align="left">CM063851</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Zeng (2006) Mol Genet Metab 89</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">L272P</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >274</td><td style="border-right:solid" align="left">CM950104</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left">Shaag (1995) Am J Hum Genet 57</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">G274R</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >277</td><td style="border-right:solid" align="left">rs78677072 </td><td style="border-right:solid" align="left">dbSNP</td><td style="border-right:solid" align="left"> Multiple independent submissions to the refSNP cluster <br>1000 Genome project</td><td style="border-right:solid" align="left">synonymous</td><td style="border-right:solid" align="left">T277T</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >278</td><td style="border-right:solid" align="left">rs140581464 </td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left"> Multiple independent submissions to the refSNP cluster <br> Validated by frequency or genotype data <br>1000Genome project</td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">V278M</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >279</td><td style="border-right:solid" align="left">rs145717248 </td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">Y279H</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >280</td><td style="border-right:solid" align="left">rs148081446 </td><td style="border-right:solid" align="left">dbSNP</td><td style="border-right:solid" align="left"> Multiple independent submissions to the refSNP cluster <br> Validated by frequency or genotype data <br>1000 Genome project</td><td style="border-right:solid" align="left">synonymous</td><td style="border-right:solid" align="left">P280P</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >280_2</td><td style="border-right:solid" align="left">CM990197</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Elpeleg (1999) J Inherit Metab Dis 22</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">P280S</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >280_3</td><td style="border-right:solid" align="left">VAR_039088</td><td style="border-right:solid" align="left">SNPdbe</td><td style="border-right:solid" align="left">Elpeleg (1999) J Inherit Metab Dis 22</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">P280L</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >281</td><td style="border-right:solid" align="left">rs141858640 </td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">V281M</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >285</td><td style="border-right:solid" align="left">rs28940279 <br> CM930046</td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe<br> OMIM<br> HGMD</td><td style="border-right:solid" align="left"> Multiple independent submissions to the refSNP cluster <br> Validated by frequency or genotype data<br> Kaul (1993) Nat Genet 5</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">E285A</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >285_2</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">E285D</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >286</td><td style="border-right:solid" align="left">rs138062143 </td><td style="border-right:solid" align="left">dbSNP</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">synonymous</td><td style="border-right:solid" align="left">A286A</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >287</td><td style="border-right:solid" align="left">CM990198</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left">Elpeleg (1999) J Inherit Metab Dis 22</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">A287T</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >288</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">Y288F</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >288_2</td><td style="border-right:solid" align="left">CM034717</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Surendran (2003) Mol Genet Metab 80</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">Y288C</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >295</td><td style="border-right:solid" align="left">CM950105</td><td style="border-right:solid" align="left">SNPdbe<br> HGMD</td><td style="border-right:solid" align="left">Shaag (1995) Am J Hum Genet 57</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">F295S</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >305</td><td style="border-right:solid" align="left">rs28940574 <br> CM940124</td><td style="border-right:solid" align="left">dbSNP<br> SNPdbe<br> OMIM<br> HGMD</td><td style="border-right:solid" align="left"> Multiple independent submissions to the refSNP cluster<br>Kaul (1994) Am J Hum Genet 55</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">A305E</td></tr> <tr bgcolor="#C1FFC1"><td style="border-right:solid" align="left" >310</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">SNPdbe</td><td style="border-right:solid" align="left"></td><td style="border-right:solid" align="left">missense</td><td style="border-right:solid" align="left">C310G</td></tr> <tr bgcolor="#BFEFFF"><td style="border-right:solid" align="left" >314</td><td style="border-right:solid" align="left">CM023608</td><td style="border-right:solid" align="left">HGMD</td><td style="border-right:solid" align="left">Zeng (2002) J Inherit Metab Dis 25</td><td style="border-right:solid" align="left">missense</td><td style="color:red;border-right:solid;border-color:black" align="left">Ter314W</td></tr> </table> </figtable> == SNP Visualization == The coding SNPs are written below the reference sequence. An 'X' denotes a nonsense mutation coding a stop codon MTSCHIAEEHIQKVAIFGGTHGNELTGVFLVKHWLENGAEIQRTGLEVKP 50 R G T R P G TR R FITNPRAVKKCTRYIDCDLNRIFDLENLGKKMSEDLPYEVRRAQEINHLF 100 A T A H T A K GPKDSEDSYDIIFDLHNTTSNMGCTLILEDSRNNFLIQMFHYIKTSLAPL 150 X V Y D E V E I F T PCYVYLIEHPSLKYATTRSIAKYPVGIEVGPQPQGVLRADILDQMRKMIK 200 RYI T F I H T A T HX F R W C L Y HALDFIHHFNEGKEFPPCAIEVYKIIEKVDYPRDENGEIAAIIHPNLQDQ 250 S EX X T K C KN T R V T X L DWKPLHPGDPMFLTLDGKTIPLGGDCTVYPVFVNEAAYYEKKEAFAKTTK 300 T P R TMHPM AATF S S D C LTLNAKSIRCCLH- 314 E G W == Hotspots == ===Visual inspection=== For the visual inspection, we looked at two kinds of reported SNPs: first, those reported by the HGMD, so they are reported to cause the Canavan Disease. Second, SNPs from dbSNP and xx that are not reported to cause the Canavan Disease (however, they are also not reported to NOT cause it). For the HGMD data, SNPs were pretty much scattered all over the structure. It was surprising for us that even many SNPs on the surface of the protein, not even close to the dimer interaction site, were also reported to cause the Canavan Disease. See <xr id="hgmd_all" /> and <xr id ="hgmd_surface"/>. <figtable id="HGMD"> <table align="center"> <tr> <td> <figure id="hgmd_all">[[File:HGMD_SNPs.png|thumb|250px|<b><xr nolink id="hgmd_all"/></b><br> Mutations of Aspartoacylase which cause the Canavan Disease residues are coloured in red. Many of these mutations are close to the binding site (around the zinc ion), as can be expected.]]</figure> </td> <td> <figure id="hgmd_surface">[[File:HGMD_SNPs_surface.png|thumb|300px|<b><xr nolink id="hgmd_surface"/></b><br> Mutations of Aspartoacylase in red - surface view. Many of these mutations that cause the Canavan Disease can be found both on the surface, far away from the binding site or the dimer interaction site, which we found surprising.]]</figure></td> </tr> </table> </figtable> For SNPs NOT reported to cause the Canavan Disease, SNPs again were scattered all over the structure. We had expected to visually be able to see some concentration of mutations in certain - apparently functionally unimportant or structurally flexible - regions, but could not validate this expectation with the given data, at least not visually. See <xr id="others_all" /> and <xr id ="others_surface"/>. <figtable id="others"> <table align="center"> <tr> <td> <figure id="others_all">[[File:SNPs_no_Canavan_report.png|thumb|250px|<b><xr nolink id="others_all"/></b><br> Mutations of Aspartoacylase residues are coloured in blue. Visually, we cannot detect a pattern or hotspots.]]</figure> </td> <td> <figure id="others_surface">[[File:SNPs_no_Canavan_report_surface.png|thumb|300px|<b><xr nolink id="others_surface"/></b><br> Mutations of Aspartoacylase in blue - surface view. Mutations that are not reported to cause the Canavan Disease can be found both on the surface, as seen in this picture, as well as on the inside of the protein (as seen on the left).]]</figure></td> </tr> </table> </figtable> ===Frequency Distribution=== Since visual inspection did not bring further enlightenment, we had a look at the frequency distribution of the disease causing and non-disease causing SNPs. These can be found in <xr id = "can"/> and <xr id="no_can"/>. Neither for the disease causing, nor for the non-disease causing SNPs, we were able to identify distinct hotspot-regions. The only exception might be the last block of mutations in <xr id = "no_can"/> close to the end of the sequence. It is curious, though, that this sequence part should be evolutionary flexible, since it includes residue 288, which is part of the binding site (but keep in mind that maybe this mutation has just not been annotated to cause the Canavan Disease. It might do it, still). <table align="center"> <tr> <td> <figure id="can">[[File:Canavan.png|thumb|800px|<b><xr nolink id="can"/></b><br> Frequency distribution of disease-causing mutations along the sequence. Mutations are fairly evenly distributed.]]</figure> </td> </tr> </table> <table align="center"> <tr> <td> <figure id="no_can">[[File:No_Canavan.png|thumb|800px|<b><xr nolink id="no_can"/></b><br> Frequency distribution of mutations not reported to cause Canavan Disease. Again, the distribution is fairly even, except for a slight accumulation towards the end of the sequence in regions 277-288.]]</figure></td> </tr> </table>

Return to Task 5 - Mapping SNPs Canavan.