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===Mutations=== ====CM994594==== Mutation: '''Tyr''' to '''Cys''' at position 231; we got it from dbSNP. Tyrosine is an highly hydrophobic amino acid due to a benzene ring in its side chain. It occupies considerably more space than the thiol group that cysteine contains. What is more, they are quite hydrophilic and do form hydrogen bonds, both of which is not true of the benzene side chain of tyrosine. This mutation is very common among Ashkenazi jews and causes Canavan's Disease. ====CM940124==== Mutation: '''Ala''' to '''Glu''' at position 305; we got it from dbSNP. Alanine has a single carbon atom in its side chain, making it hydrophobic and very small. Glutamic acid is an entirely different animal, with a total of three carbon atoms in its side chain, the last of which being part of a carbon acid group. This makes it highly hydrophilic and also leads to a negative charge in the carboxyl group at physiological pH values. This mutation is very common among Ashkenazi jews and causes Canavan's Disease. ====RS104894553==== Mutation: '''Arg''' to '''His''' at position 71; we got it from HGMD. Arginine is hydrophilic, quite large, with a long side chain and three nitrogen atoms at the end, the chemistry of which gives it a positive charge at physiological pHs. Substituting it by Histidine takes away the charge and substitutes the outmost carbon atom and all of the nitrogen-containing groups with an imidazole group. This leads to a slight decrease in hydrophobicity and not much else. This mutation is the most common disease-causing mutation among non-jews. ====RS104894551==== Mutation: '''Glu''' to '''Gly''' at position 24; we got it from HGMD. Glutamic acid contains a carboxyl group and carries a negative charge at physiological pHs. Glycine doesn't have anything in the way of a proper side chain, with a hydrogen atom taking its place instead. While glutamic acid is quite hydrophilic, glycine has the chemical properties of the amino acid backbone, which is fairly aliphatic. ====RS104894548==== Mutation: '''Cys''' to '''Arg''' at position 152; we got it from HGMD. Cysteine contains a thiol group, which is hydrophilic and forms hydrogen bridges; Arginine is negatively charged at physiological pHs and hydrophilic and occupies much more space than cysteine. ====RS80099330==== Mutation: '''Met''' to '''Thr''' at position 82; we got it from HGMD. Methionine is a hydrophobic amino acid; Threonine, by contrast, contains an hydroxyl group in the middle of its side chain, which makes it hydrophilic and polar. ====CM063847==== Mutation: '''Thr''' to '''Ile''' at position 166; we got it from dbSNP. The hydrophilic and polar threonine structurally differs not very much from Isoleucine; for the hydroxyl group, a C atom is substituted, and the side chain elongated by another C. ====CM990193==== Mutation: '''Pro''' to '''His''' at position 183; we got it from dbSNP. Proline is hydrophobic and contains a hetero-pentacyclus with one thiol group. Histidin contains such a cyclus, too, but with another nitrogen atom. It carries a positive charge and is hydrophilic. ====CM990195==== Mutation: '''Met''' to '''Arg''' at position 195; we got it from dbSNP. Methionine is hydrophobic; Arginine is positively charged and hydrophilic and more spacious than methionine. ====CM055097==== Mutation: '''Lys''' to '''Glu''' at position 213; we got it from dbSNP. Lysine contains a positively charged nitrogen atom part of an ammonium group; Glutamic acid carries a negative charge on a carboxyl group. Both are hydrophilic and of comparable size. ===PSSM=== <span style="background-color: orange">Mutated</span> / <span style="background-color: violet">Wildtype</span> <code> A R N D C Q E G H I L K M F P S T W Y V A R N D C Q E G H I L K M F P S T W Y V 24 E -4 -3 -3 -1 -7 0 <span style="background-color: violet">8</span> <span style="background-color: orange">-5</span> -3 -6 -6 -2 -5 -6 -4 -3 -4 -6 -5 -6 0 0 0 0 0 1 <span style="background-color: violet">99</span> <span style="background-color: orange">0</span> 0 0 0 0 0 0 0 0 0 0 0 0 2.24 1.67 71 R -4 <span style="background-color: violet">8</span> -3 -2 -6 -2 -3 -5 <span style="background-color: orange">-1</span> -5 -4 -1 1 -5 -5 -3 -4 -5 -4 -5 0 <span style="background-color: violet">88</span> 0 3 0 0 0 0 <span style="background-color: orange">1</span> 0 0 0 5 0 0 0 0 0 0 0 1.96 1.46 82 M 1 -2 1 2 -1 0 -1 1 0 -1 -2 -1 <span style="background-color: violet">2</span> -3 1 -1 <span style="background-color: orange">2</span> -3 -2 -1 10 2 6 10 1 4 4 12 3 4 4 3 <span style="background-color: violet">5</span> 1 6 5 <span style="background-color: orange">14</span> 0 2 5 0.15 1.53 152 C -2 <span style="background-color: orange">-3</span> -1 1 <span style="background-color: violet">3</span> -2 -2 -3 -2 3 -1 -4 2 -2 -2 -3 -2 -5 -1 5 2 <span style="background-color: orange">2</span> 3 8 <span style="background-color: violet">6</span> 2 2 2 1 16 3 1 4 1 3 2 2 0 2 39 0.64 2.02 166 T 2 -2 -1 -1 -2 -2 -1 -1 -1 <span style="background-color: orange">-3</span> -2 -4 -2 3 -2 2 <span style="background-color: violet">3</span> 1 3 -1 15 2 2 3 1 1 5 5 1 <span style="background-color: orange">1</span> 4 1 1 12 2 15 <span style="background-color: violet">16</span> 2 10 3 0.34 2.09 183 P 0 -1 0 -1 1 0 -1 1 <span style="background-color: orange">0</span> -4 -1 -1 0 -1 <span style="background-color: violet">4</span> 0 -1 4 0 -2 9 3 4 4 3 4 3 12 <span style="background-color: orange">3</span> 0 6 4 3 3 <span style="background-color: violet">17</span> 6 3 6 3 3 0.26 1.80 195 M 1 <span style="background-color: orange">-1</span> -4 -1 2 -1 -1 1 1 1 0 -4 <span style="background-color: violet">3</span> 1 -5 -1 2 -5 0 1 12 <span style="background-color: orange">3</span> 0 3 5 3 3 9 4 9 7 0 <span style="background-color: violet">9</span> 5 0 4 11 0 4 8 0.21 1.85 213 K -1 1 0 2 1 0 <span style="background-color: orange">0</span> -1 1 -1 -1 <span style="background-color: violet">0</span> 1 0 1 -1 0 -5 0 -1 6 7 4 10 3 5 <span style="background-color: orange">5</span> 4 3 4 8 <span style="background-color: violet">7</span> 3 4 8 5 6 0 3 5 0.07 2.08 231 Y 0 0 -4 -4 <span style="background-color: orange">-2</span> -2 -2 -3 -4 -1 0 2 1 2 -4 -1 -2 6 <span style="background-color: violet">4</span> -1 10 6 0 1 <span style="background-color: orange">1</span> 1 3 2 0 3 8 14 4 8 1 4 2 13 <span style="background-color: violet">15</span> 5 0.52 1.95 305 A <span style="background-color: violet">3</span> -4 -5 -5 2 -4 <span style="background-color: orange">-4</span> -4 -5 1 2 -4 -2 0 -4 -2 -3 -5 -3 5 <span style="background-color: violet">24</span> 0 0 0 4 0 <span style="background-color: orange">0</span> 0 0 7 17 0 0 3 0 3 0 0 0 41 0.71 1.09 </code> ===Secondary Structure=== <code> ASPA: MTSCHIAEEHIQKVAIFGGTHGN<span style="background-color:lightgreen">E</span>LTGVFLVKHWLENGAEIQRTGLEVKPFITNPRAVKKCTRYID<br> MUT:&nbsp; MTSCHIAEEHIQKVAIFGGTHGN<span style="background-color:orange">G</span>LTGVFLVKHWLENGAEIQRTGLEVKPFITNPRAVKKCTRYID<br> SS: &nbsp; ------------EEEEEEEE------HHHHHHHHHH---------EEEEEEEE-HHHHHH-----H<br> <br> ASPA: CDLN<span style="background-color:lightgreen">R</span>IFDLENLGKK<span style="background-color:lightgreen">M</span>SEDLPYEVRRAQEINHLFGPKDSEDSYDIIFDLHNTTSNMGCTLILEDSR<br> MUT:&nbsp; CDLN<span style="background-color:orange">H</span>IFDLENLGKK<span style="background-color:orange">T</span>SEDLPYEVRRAQEINHLFGPKDSEDSYDIIFDLHNTTSNMGCTLILEDSR<br> SS: &nbsp; ---------------------HHHHHHHHHHHHHH-------EEEEEE-----------EEEE---<br> <br> ASPA: NNFLIQMFHYIKTSLAPLP<span style="background-color:lightgreen">C</span>YVYLIEHPSLKYA<span style="background-color:lightgreen">T</span>TRSIAKYPVGIEVGPQ<span style="background-color:lightgreen">P</span>QGVLRADILDQ<span style="background-color:lightgreen">M</span>RKM<br> MUT:&nbsp; NNFLIQMFHYIKTSLAPLP<span style="background-color:orange">R</span>YVYLIEHPSLKYA<span style="background-color:orange">I</span>TRSIAKYPVGIEVGPQ<span style="background-color:orange">H</span>QGVLRADILDQ<span style="background-color:orange">R</span>RKM<br> SS: &nbsp; -HHHHHHHHHHHH------EEEEEE---------HHEE----EEEEE---------HHHHHHHHHH<br> <br> ASPA: IKHALDFIHHFNEG<span style="background-color:lightgreen">K</span>EFPPCAIEVYKIIEKVD<span style="background-color:lightgreen">Y</span>PRDENGEIAAIIHPNLQDQDWKPLHPGDPMFLT<br> MUT:&nbsp; IKHALDFIHHFNEG<span style="background-color:orange">E</span>EFPPCAIEVYKIIEKVD<span style="background-color:orange">C</span>PRDENGEIAAIIHPNLQDQDWKPLHPGDPMFLT<br> SS: &nbsp; HHHHHHHHHHH----------EEEEEEEEEE----------EEEE----------------HHE--<br> <br> ASPA: LDGKTIPLGGDCTVYPVFVNE<span style="background-color:lightgreen">A</span>AYYEKKEAFAKTTKLTLNAKSIRCCLH<br> MUT:&nbsp; LDGKTIPLGGDCTVYPVFVNE<span style="background-color:orange">E</span>AYYEKKEAFAKTTKLTLNAKSIRCCLH<br> SS: &nbsp; ----EEEE----EEEEEEE-----HHH-HHHHHHHHEEE-----EEEE-</code> ===Multiple Sequence Alignment=== We calculated our MSA using T-Coffee [[File:homologe.png|200px|thumb|left|alt text]] ===Table of Results=== {| class="wikitable" border="1" style="text-align:center; border-spacing:0;" ! Mutation || Pos. || Blosum Score || Worst? || PAM250 Score || Worst? || PAM1 Score || Worst? || PSSP Mutated || Wildtype || MSA Mutated || Wildtype || Polyphen Prediction || Score || Sift Prediction || Score || Median Conservation || SNAP Prediction || Reliability || Exp. Accuracy |- | Tyr->Cys || 231 || -2 || no || -0.5 || no || 3 || no || -2 || 15 || 0.0% || 73.7% || damaging || 1.0 || affect || 0.00 || 3.02 || Non-neutral || 5 || 87% |- | Ala->Glu || 305 || -1 || no || 0 || no || 17 || no || -4 || 3 || 0.0% || 68.8% || damaging || 1.0 || affect || 0.02 || 3.14 || Non-neutral || 3 || 78% |- | Arg->His || 71 || 0 || no || 0.6 || no || 8 || no || -1 || 8 || 0.0% || 100.0% || damaging || 1.0 || affect || 0.01 || 3.02 || Non-neutral || 6 || 93% |- | Glu->Gly || 24 || -2 || no || -0.8 || no || 7 || no || -5 || 8 || 0.0% || 100.0% || damaging || 1.0 || affect || 0.00 || 3.02 || Non-neutral || 7 || 96% |- | Cys->Arg || 152 || -3 || yes || -2.2 || yes || 1 || no || -3 || 3 || 0.0% || 100.0% || damaging || 0.999 || affect || 0.01 || 3.07 || Non-neutral || 6 || 93% |- | Met->Thr || 82 || -1 || no || -0.6 || no || 6 || no || 14 || 2 || 0.0% || 57.9% || benign || 0.0 || tolerated || 0.16 || 3.02 || Non-neutral || 0 || 58% |- | Thr->Ile || 166 || -1 || no || -0.6 || no || 7 || no || 1 || 16 || 0.0% || 73.7% || damaging || 1.0 || affect || 0.04 || 3.07 || Non-neutral || 2 || 70% |- | Pro->His || 183 || -2 || no || -1.1 || no || 3 || no || 0 || 4 || 5.3% || 94.7% || damaging || 1.0 || affect || 0.00 || 3.07 || Non-neutral || 6 || 93% |- | Met->Arg || 195 || -1 || no || -1.7 || no || 4 || no || -1 || 3 || 0.0% || 94.7% || damaging || 0.991 || affect || 0.03 || 3.04 || Non-neutral || 5 || 87% |- | Lys->Glu || 213 || 1 || no || 1.2 || no || 4 || no || 0 || 0 || 0.0% || 73.7% || benign || 0.014 || tolerated || 0.83 || 3.02 || Neutral || 3 || 78% |}

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