Task 5: Researching SNPs
In this task we are to research SNPs associated with our protein odba_human, in different databases.
HGMD( free version )
HGMD - Human Gene Mutation Database HGMD represents a collection of published mutations. This means HGMD contains only mutations leading to a disease. In our case publications between 1993-2008 are covered. The sequences and a list of all listed mutations can be found in the protocol-msud-task5 protocol
HGMD - BCKDHA (non-profit) | |
Mutation type | number of entries |
Missense/nonsense | 36 |
small deletions | 3 |
small insertions | 1 |
Gross deletions | 2 |
complex rearrangements | 1 |
dbSNP
Here is a list of the silent mutations we found in dbSNP. The complete list of all mutations from dbSNP (including missense and frameshift mutations) can be found in the protocol-msud-task5 protocol.
Insertion or deletion of nucleotides can cause frameshifts. As the amino acid code is triplet based, inserting or deleting a single nucleotide from within the sequence will not only cause a amino acid to be changed, but will move all following codons out of frame, changing every fololowing amino acid after die insertion or deletion. For a graphical representation please see figure 1. Insertions or deletions are less severe when they appear near the end of an exon, as this limits the number of amino acids changed.
rs Cluster Id | Function | AA Pos | Codon Pos | From Nucleotide | To Nucleotide | From AA | To AA |
---|---|---|---|---|---|---|---|
rs17173144 | synonymous | 5 | 3 | C | T | Ile [I] | Ile [I] |
rs34541442 | synonymous | 12 | 1 | C | A | Arg [R] | Arg [R] |
rs140322984 | synonymous | 21 | 3 | C | T | Ala [A] | Ala [A] |
rs62637712 | synonymous | 38 | 3 | C | G, T | Pro [P] | Pro [P], Pro [P] |
rs80014754 | synonymous | 39 | 3 | C | A | Pro [P] | Pro [P] |
rs138025447 | synonymous | 71 | 3 | C | T | Asn [N] | Asn [N] |
rs143167070 | synonymous | 80 | 3 | C | T | Arg [R] | Arg [R] |
rs148571328 | synonymous | 96 | 3 | C | T | His [H] | His [H] |
rs11549937 | synonymous | 97 | 3 | G | C | Leu [L] | Leu [L] |
rs142967869 | synonymous | 98 | 3 | G | A | Pro [P] | Pro [P] |
rs150700696 | synonymous | 112 | 3 | T | G | Leu [L] | Leu [L] |
rs143608852 | synonymous | 140 | 3 | G | A | Thr [T] | Thr [T] |
rs146804716 | synonymous | 141 | 3 | C | T | His [H] | His [H] |
rs144995574 | synonymous | 206 | 3 | C | T | Ser [S] | Ser [S] |
rs10404506 | synonymous | 213 | 3 | C | T | Ile [I] | Ile [I] |
rs114716391 | synonymous | 216 | 3 | G | T | Ala [A] | Ala [A] |
rs151227241 | synonymous | 221 | 3 | C | T | Tyr [Y] | Tyr [Y] |
rs146932786 | synonymous | 236 | 3 | C | T | Phe [F] | Phe [F] |
rs137960127 | synonymous | 248 | 3 | C | T | Ala [A] | Ala [A] |
rs61737367 | synonymous | 280 | 3 | C | T | Arg [R] | Arg [R] |
rs187669174 | synonymous | 297 | 3 | C | T | Arg [R] | Arg [R] |
rs139390622 | synonymous | 308 | 3 | C | T | Asn [N] | Asn [N] |
rs190858285 | synonymous | 316 | 3 | G | T | Arg [R] | Arg [R] |
rs284652 | synonymous | 324 | 3 | C | T | Phe [F] | Phe [F] |
rs55940366 | synonymous | 325 | 3 | C | T | Leu [L] | Leu [L] |
rs144276456 | synonymous | 347 | 3 | G | A | Ser [S] | Ser [S] |
rs190202447 | synonymous | 383 | 3 | G | A | Arg [R] | Arg [R] |
rs145595627 | synonymous | 403 | 3 | C | T | Pro [P] | Pro [P] |
rs4674 | synonymous | 407 | 3 | A | C, G, T | Leu [L] | Leu [L], Leu [L], Leu [L] |
rs147021347 | synonymous | 417 | 3 | C | T | Pro [P] | Pro [P] |
rs34492894 | synonymous | 420 | 3 | C | T | Leu [L] | Leu [L] |
rs148224513 | synonymous | 443 | 3 | C | T | Phe [F] | Phe [F] |
SNPdbe
As SNPdbe contains predicted and experimental SNPs, we first have to parse the output of the database search. The list of all mutations can be found in the Protocol-msud-task5 protocol Unfortunately we only found not validated SNPs. Among those, 8 leading to MSUP.
SNPedia
In SNPedia wie found the folowing four SNPs for MSUD.
- rs12021720
- rs17856511
- rs28934895, also known as R183P (the most common SNP in Ashkenazi Jews); the risk genotype is CC
- rs28940288
of those the first two are merged into one in dbSNP and do not concern the BCKDHA protein. The same goes for the third entry and the fourth is already contained in dbSNP.
OMIM
OMIM contains 9 entries for BCKDHA( odba_human - 608348 ), all leading to MSUD. As reference sequence Uniprot is given.
Number | Phenotype | Mutation | dbSNP |
.0001 | MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA | BCKDHA, TYR393ASN | - |
.0002 | MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA | BCKDHA, 8-BP DEL, 887-894 | - |
.0003 | MAPLE SYRUP URINE DISEASE,INTERMEDIATE, TYPE IA | BCKDHA, GLY245ARG | - |
.0004 | MAPLE SYRUP URINE DISEASE, INTERMEDIATE, TYPE IA MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA, INCLUDED |
BCKDHA, PHE364CYS | - |
.0005 | MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA | BCKDHA, ARG220TRP | - |
.0006 | MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA | BCKDHA, GLY204SER | - |
.0007 | MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA | BCKDHA, THR265ARG | - |
.0008 | MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA | BCKDHA, CYS219TRP | - |
.0009 | MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA | BCKDHA, 1-BP DEL, 117C | - |
mutationmap
We first (with little sucess) tried to build a graphical per-nucleotide representation of the Sequence the result can be found in figure 2.
After that we decided to go for a structural representation using pymol. Two images of the colored representation can be found below in figures 3 and 4.
To actually take a look at the mapping we recommend directly loading it in pymol, for wich we provide the pymol session file here.
conclusion
will be added on tuesday...