Task 5: Mapping point mutations
Contents
Task description
A detailed task description can be found here: Mapping point mutations
SNP databases
HGMD
- HGMD
- Searched for PAH
- 429 Missense/Nonsense mutations known by HGMD Professional
There are several mutation types known for PAH:
- Missense/nonsense
- Splicing
- Regulatory
- Small deletions
- Small insertions
- Small indels
- Gross deletions
- Gross insertions/duplications
- Complex rearrangements
One additional category of mutation is known, but is not recorded for PAH
- Repeat variations
Reference Sequence
The reference sequence is given by the accession number NM_000277.1, whose entry contains the following amino acid sequence:
MSTAVLENPGLGRKLSDFGQETSYIEDNCNQNGAISLIFSLKEEVGALAKVLRLFEEN DVNLTHIESRPSRLKKDEYEFFTHLDKRSLPALTNIIKILRHDI GATVHELSRDKKKDTVPWFPRTIQELDRFANQILSYGAELDADHPGFKDPVYRARRKQ FADIAYNYRHGQPIPRVEYMEEEKKTWGTVFKTLKSLYKTHACYEYNHIFPLLEKYCG FHEDNIPQLEDVSQFLQTCTGFRLRPVAGLLSSRDFLGGLAFRVFHCTQYIRHGSKPM YTPEPDICHELLGHVPLFSDRSFAQFSQEIGLASLGAPDEYIEKLATIYWFTVEFGLC KQGDSIKAYGAGLLSSFGELQYCLSEKPKLLPLELEKTAIQNYTVTEFQPLYYVAESF NDAKEKVRNFAATIPRPFSVRYDPYTQRIEVLDNTQQLKILADSINSEIGILCSALQK IK
SNPs
SNPdb
Methodology
Results
We could find the following silent mutations in dbSNP:
| Identifier | AA-Position | Reference Triplet | Mutated Triplet | Reference Allele | Mutated Allele | Frame | Reference Residue | Mutated Residue |
|---|---|---|---|---|---|---|---|---|
| rs117308669 | 65 | GAA | GAG | A | G | 3 | E | E |
| rs75065106 | 257 | CTG | TTG | C | T | 1 | L | L |
| rs62651567 | 322 | ACA | ACG | A | G | 3 | T | T |
| rs62508648 | 366 | CTG | CTA | G | A | 3 | L | L |
| rs61747292 | 320 | CTC | CTT | C | T | 3 | L | L |
| rs59326968 | 425 | AAT | AAC | T | C | 3 | N | N |
| rs17852374 | 35 | TCA | TCG | A | G | 3 | S | S |
| rs1801152 | 413 | TAC | TAT | C | T | 3 | Y | Y |
| rs1801151 | 399 | AGG | CGG | A | C | 1 | R | R |
| rs1801150 | 398 | GTA | GTT | A | T | 3 | V | V |
| rs1801147 | 202 | TGC | TGT | C | T | 3 | C | C |
| rs1801146 | 136 | AGC | AGT | C | T | 3 | S | S |
| rs1801145 | 9 | GGC | GGG | C | G | 3 | G | G |
| rs1126758 | 231 | CAG | CAG | A | G | 3 | Q | Q |
| rs1042503 | 244 | GTG | GTA | G | A | 3 | V | V |
| rs772897 | 384 | CTG | CTC | G | C | 3 | L | L |
Comparing the annotation of HGMD and SNPdb
Alignment of the reference sequences
We decided to use the sequence of PAH of Uniprot (see UniProt).
MSTAVLENPGLGRKLSDFGQETSYIEDNCNQNGAISLIFSLKEEVGALAKVLRLFEENDV
NLTHIESRPSRLKKDEYEFFTHLDKRSLPALTNIIKILRHDIGATVHELSRDKKKDTVPW
FPRTIQELDRFANQILSYGAELDADHPGFKDPVYRARRKQFADIAYNYRHGQPIPRVEYM
EEEKKTWGTVFKTLKSLYKTHACYEYNHIFPLLEKYCGFHEDNIPQLEDVSQFLQTCTGF
RLRPVAGLLSSRDFLGGLAFRVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFA
QFSQEIGLASLGAPDEYIEKLATIYWFTVEFGLCKQGDSIKAYGAGLLSSFGELQYCLSE
KPKLLPLELEKTAIQNYTVTEFQPLYYVAESFNDAKEKVRNFAATIPRPFSVRYDPYTQR
IEVLDNTQQLKILADSINSEIGILCSALQKIK
Alignment with the reference sequence used in HGMD
The resulting alignment shows a 100% identity without any gaps. Therefore it is a "self-alignment".
