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>