Task 8: Sequence-based mutation analysis

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Lab journal task 8

Mutation selection

<figtable id="mutations">

Table 1: List of the 10 selected mutations from HGMD and dbSNP.

mutations
nucleotide change	amino acid change
	Val53Met
	His63Asp
	Arg67His
	Met97Ile
	Asn130Ser
	Glu168Gln
	Leu183Pro
	Thr217Ile
	Cys282Tyr
	Arg330Met

</figtable>

Mutation analysis results

<figtable id="summary">

Table 2: Summary of the results of analysis of all mutations.

reference	mutation	pyhsicochemical properties		strucural properties		conservation			prediction programms				consensus
		from	to	pymol visualisation	secondary structure	substitution matrix	PSSM	MSA	SIFT	Polyphen2	MutationTaster	SNAP
	Val53Met	brached chain, nonpolar, neutral charge	sulfur containing, nonpolar, neutral charge	Val53Met mutation with valine in yellow and methionine in red.
	His63Asp	aromatic ring, basic polar, mainly neutral charge	acidic polar, negative charge	File:His62asp.png His63Asp mutation with histidine in yellow and aspartic acid in red.
	Arg67His
	Met97Ile
	Asn130Ser
	Glu168Gln
	Leu183Pro
	Thr217Ile
	Cys282Tyr
	Arg330Met			Could not be visualized because this resdiue is not contained in the the pdb structure.

</figtable>

All results from the mutation analysis are summarised in <xr id="summary"/>. Physicochemical properties are specified as characteristics of the aa, side chain polarity and charge.

Val53Met
The main effect of the change from valine to methonine is mainly due to the structure, because both aa are nonpolar and neutral. Methionine is linear and valine has a branched structure. As can be seen in the picture, this could lead to clashes with the alpha helix above the methionine.
His63Asp
h This mutation is very likely disease causing, because the basic aa histidine is replaced by the acidic aspartic acid. Besides, histidine is mainly neutral whereas the aspartic acid is negatively charged.