Difference between revisions of "Sequence-based mutation analysis Gaucher Disease"

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[[File:structure_all.png|thumb|400px|left|<caption>2nt0_A along with the selected wildtype residues from <xr id="tab:mutations"/> in blue.</caption>]]
  
[[File:structure_all.png|thumb|400px|left|<caption>2nt0_A along with the selected wildtype residues from <xr id="tab:mutations"/> in blue.</caption>]]
 
</figure>
  
</figure>
  +
  +
<br clear="all"/>
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== Substitution scores ==
  +
  +
=== BLOSUM62 scores ===
  +
The scores were taken from the [[BLOSUM62 matrix|BLOSUM62 matrix]].
  +
  +
<figtable id="tab:subst_blosum">
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{| style="border-collapse: separate; border-style: solid; border-spacing: 0; border-width: 2px 0 2px 0; text-align:center" width="450px"
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|- style="background-color: lightgrey"
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! Nr !! Mutation !! Score mutation !! Score min !! Score max
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|-
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| colspan=5 style="border-collapse: separate; border-style: solid; border-spacing: 0; border-width: 1px 0 0 0"|
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|-
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| 1 || H99R || 0 || -3 || 8
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|-
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| 2 || V211I || 3 || -3 || 4
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|-
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| 3 || E150K || 1 || -4 || 5
  +
|-
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| 4 || L236P || -3 || -4 || 4
  +
|-
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| 5 || W248R || -3 || -4 || 11
  +
|-
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| 6 || L509P || -3 || -4 || 4
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|-
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| 7 || W351C || -2 || -4 || 11
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|-
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| 8 || A423D || -2 || -3 || 4
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|-
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| 9 || D482N || 1 || -4 || 6
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|-
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| 10 || R83S || -1 || -3 || 5
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|}
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<caption>BLOSUM62 scores of the selected mutations</caption>
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</figtable>
  +
  +
=== PSSM of all hits===
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[[PSSM|PSSM]].
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  +
<figtable id="tab:subst_pssm_all">
  +
{| style="border-collapse: separate; border-style: solid; border-spacing: 0; border-width: 2px 0 2px 0; text-align:center" width="500px"
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|- style="background-color: lightgrey"
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! Nr !! Mutation !! Score mutation !! Score min !! Score max !! Conservation
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|-
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| colspan=6 style="border-collapse: separate; border-style: solid; border-spacing: 0; border-width: 1px 0 0 0"|
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|-
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| 1 || H99R || 0 || -4 || 2
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|-
  +
| 2 || V211I || 4 || -4 || 4
  +
|-
  +
| 3 || E150K || 0 || -4 || 5
  +
|-
  +
| 4 || L236P || 0 || -3 || 1
  +
|-
  +
| 5 || W248R || -2 || -3 || 4
  +
|-
  +
| 6 || L509P || -6 || -6 || 4
  +
|-
  +
| 7 || W351C || -3 || -6 || 9
  +
|-
  +
| 8 || A423D || -3 || -3 || 3
  +
|-
  +
| 9 || D482N || 4 || -4 || 4
  +
|-
  +
| 10 || R83S || 0 || -3 || 2
  +
|}
  +
<caption>Position specific substitution scores derived from all significant hits after 5 rounds PSI-BLAST.</caption>
  +
</figtable>

Revision as of 07:41, 15 June 2012

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 Structure nr1.png
2 V211I exposed C no Structure nr2.png
3 E150K exposed C no Structure nr3.png
4 L236P exposed C no Structure nr4.png
5 W248R buried H yes Structure nr5.png
6 L509P exposed S yes Structure nr6.png
7 W351C exposed S yes Structure nr7.png
8 A423D buried C yes Structure nr8.png
9 D482N exposed C yes Structure nr9.png
10 R83S exposed C yes Structure nr10.png

Location of mutations in 2nt0_A. Blue: wildtype; Red: mutant. </figtable>

<figure id="fig:structure_all">

2nt0_A along with the selected wildtype residues from <xr id="tab:mutations"/> in blue.

</figure>


Substitution scores

BLOSUM62 scores

The scores were taken from the BLOSUM62 matrix.

<figtable id="tab:subst_blosum">

Nr Mutation Score mutation Score min Score max
1 H99R 0 -3 8
2 V211I 3 -3 4
3 E150K 1 -4 5
4 L236P -3 -4 4
5 W248R -3 -4 11
6 L509P -3 -4 4
7 W351C -2 -4 11
8 A423D -2 -3 4
9 D482N 1 -4 6
10 R83S -1 -3 5

BLOSUM62 scores of the selected mutations </figtable>

PSSM of all hits

PSSM.

<figtable id="tab:subst_pssm_all">

Nr Mutation Score mutation Score min Score max Conservation
1 H99R 0 -4 2
2 V211I 4 -4 4
3 E150K 0 -4 5
4 L236P 0 -3 1
5 W248R -2 -3 4
6 L509P -6 -6 4
7 W351C -3 -6 9
8 A423D -3 -3 3
9 D482N 4 -4 4
10 R83S 0 -3 2

Position specific substitution scores derived from all significant hits after 5 rounds PSI-BLAST. </figtable>

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