Task 5: Mapping point mutations

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Revision as of 20:09, 16 June 2011 by Pfeiffenberger (talk | contribs) (SNPdb)

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".

Alignment with the reference sequence used in SNPdb

Mapping

Discussion