Sequence-based mutation analysis Gaucher Disease
The aim of this task was to carry out a thorough analysis of ten mutations and to classify them as disease-causing and non-disease causing. The mutations have been selected by another group from our [Researching SNPs Gaucher Disease|set of collected mutations] such that their impact had been unknown for us prior to this task. Technical details are reported in our protocol.
Mutations
<figtable id="tab:mutations">
| Nr | Position | From | To |
|---|---|---|---|
| 1 | 99 | H | R |
| 2 | 211 | V | I |
| 3 | 150 | E | K |
| 4 | 236 | L | P |
| 5 | 248 | W | R |
| 6 | 509 | L | P |
| 7 | 351 | W | C |
| 8 | 423 | A | D |
| 9 | 482 | D | N |
| 10 | 83 | R | S |
Randomly selected mutations from HGMD and dbSNP which were used for the sequence-based mutation analysis. </figtable>
Physicochemical properties
<figtable id="tab:props">
| Nr | Wildtype | Mutant | Severe change | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| AA | Charge | Polarity | Size | Aromatic | AA | Charge | Polarity | Size | Aromatic | ||
| 1 | H | negative | polar | large | no | R | negative | polar | large | no | no |
| 2 | V | neutral | unpolar | medium | no | I | neutral | unpolar | medium | no | no |
| 3 | E | positive | polar | large | no | K | negative | polar | large | no | yes |
| 4 | L | neutral | unpolar | medium | no | P | neutral | unpolar | medium | no | no |
| 5 | W | neutral | unpolar | large | yes | R | negative | polar | large | no | yes |
| 6 | L | neutral | unpolar | medium | no | P | neutral | unpolar | medium | no | no |
| 7 | W | neutral | unpolar | large | yes | C | neutral | polar | small | no | yes |
| 8 | A | neutral | unpolar | small | no | D | positive | polar | medium | no | yes |
| 9 | D | positive | polar | medium | no | N | neutral | polar | medium | no | no |
| 10 | R | negative | polar | large | no | S | neutral | polar | small | no | no |
Physicochemical properiets of the wildtype and mutatant amino acid which were used to classify the mutation as severe or non-severe. </figtable>
Structural analysis
<figtable id="tab:structure">
| Nr | Mutation | Accessibility | 2nd structure | Domain region | Mutation |
|---|---|---|---|---|---|
| 1 | H99R | exposed | C | no | 
|
| 2 | V211I | exposed | C | no | 
|
| 3 | E150K | exposed | C | no | 
|
| 4 | L236P | exposed | C | no | 
|
| 5 | W248R | buried | H | yes | 
|
| 6 | L509P | exposed | S | yes | 
|
| 7 | W351C | exposed | S | yes | 
|
| 8 | A423D | buried | C | yes | 
|
| 9 | D482N | exposed | C | yes | 
|
| 10 | R83S | exposed | C | yes | 
|
Location of mutations in 2nt0_A. Blue: wildtype; Red: mutant. </figtable>
<figure id="fig:structure_all">
</figure>
