Lab journal Task 7
Contents
HGMD
The HFE accession number in HGMD is NM_000410.3 (transcript variant 1 http://www.ncbi.nlm.nih.gov/nuccore/NM_000410.3). the nucleotide sequence was downloaded in fasta format and then translated to the protein sequence with http://molbiol.ru/eng/scripts/01_13.html using the first reading frame.
dbSNP
There are several different isoforms for the HFE protein. We decided to look at isoform 1 precursor (http://www.ncbi.nlm.nih.gov/protein/NP_000401.1) because there is the most data for this isoform and also because this isoform is used in HGMD. The corresponding mRNA sequence for this protein is the transcript variant 1 (http://www.ncbi.nlm.nih.gov/nuccore/NM_000410.3).
The dbSNP webserver was search for "SNP" and the following query was used: "synonymous-codon"[Function_Class] AND HFE[GENE] AND "human"[ORGN] AND "snp"[SNP_CLASS]. We used the graphic summary display of the results. Under the sequence line of each hit are several links, amongs others a link to the "Gene view". All different types of SNPs in the HFE gene can be listed in the geneView. This table was used to used to extract all mutations for the protein NP_000401 and especially the synonymous ones. and to extract the numbers of the different SNPs in the HFE gene.
SNPdbe
SNPdbe was searched for the protein "NP_000401". The results were downloaded as textfile and analysed with R.
OMIM
Omim was searched for "HFE". The first result links to the page of " * 613609. HFE GENE; HFE". It contains a section "Allelic variants" containing several publicated mutations that can also be viewed as a table (http://omim.org/allelicVariant/613609). We only included results for the protein sequence of "NP_000401" that was also used for SNPdbe.
Mutation map
The reference sequence for the HFE protein in all four databases is the same, because we only collected mutations from one mRNA transcript. Therefore, we did not have to map the codon numbers of different databases. The two domains were selected using the SCOP annotation: MHC antigen-recognition domain (4-181) and Immunglobulin domain (182-275). Since the reference sequence contains 22 residues before the start of the pdb structure sequence (1A6Z,A), 22 was added to positions of the domains to get the corresponding indices for the reference sequence.
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<figtable id="hgmd">
| accession | codon position | aa change | disease association | mutation type |
|---|---|---|---|---|
| rs149342416, CM032270 | 6 | Arg -> Ser | hemochromatosis | missense |
| rs114758821 | 7 | Pro -> Pro | N/A | synonymous |
| rs368895240 | 10 | Leu -> Leu | N/A | synonymous |
| rs201657128 | 14 | Leu -> Val | N/A | missense |
| rs143662783 | 17 | Thr -> Ile | N/A | missense |
| rs148161858 | 23 | Arg -> His | N/A | missense |
| rs2242956 | 35 | Met -> Thr | N/A | missense |
| rs377254261 | 37 | Ala -> Val | N/A | missense |
| CM091838 | 46 | Leu -> Trp | hemochromatosis | missense |
| rs28934889, CM994469 | 53 | Val -> Met | hemochromatosis | missense |
| rs147297176 | 58 | Phe -> Phe | N/A | synonymous |
| rs28934890, rs111033557, CM994470 | 59 | Val -> Met | hemochromatosis | missense |
| rs1799945, CM960827 | 63 | His -> Asp | In hereditary haemochromatosis (HH) (PMD) | missense |
| rs147426902, HM971246, | 63 | His -> His | N/A | synonymous |
| rs1800730, CM990718 | 65 | Ser -> Cys | hemochromatosis | missense |
| CM033969 | 66 | Arg -> Cys | hemochromatosis | missense |
| rs139523708 | 67 | Arg -> His | N/A | missense |
| CM020721 | 71 | Arg -> Term | hemochromatosis | nonsense |
| rs62625342 | 76 | Ser -> Ser | N/A | synonymous |
| rs28934597, CM990719 | 93 | Gly -> Arg | hemochromatosis (SwissVar). In hemochromatosis (PMD) | missense |
| rs376650371 | 97 | Met -> Ile | N/A | missense |
| rs28934596, CM990720 | 105 | Ile -> Thr | hemochromatosis (SwissVar). In hemochromatosis (PMD) | missense |
| rs199988202 | 106 | Met -> Thr | N/A | missense |
| rs28934595, CM990721 | 127 | Gln -> His | hemochromatosis (SwissVar). In variegate porphyria (VP) (PMD) | missense |
| rs200706856, CM091839 | 129 | Asp -> Asn | hemochromatosis | missense |
| rs201885016 | 130 | Asn -> Ser | N/A | missense |
| rs369790080 | 132 | Thr -> Thr | N/A | synonymous |
| CM091840 | 138 | Tyr -> Term | hemochromatosis | nonsense |
| rs372789940 | 141 | Asp -> Asn | N/A | missense |
| rs199879669 | 157 | Ala -> Pro | N/A | missense |
| rs149662565 | 160 | Pro -> Thr | N/A | missense |
| rs145475682 | 162 | Ala -> Ser | N/A | missense |
| rs148480830 | 162 | Ala -> Ala | N/A | synonymous |
| rs144170531 | 166 | Lys -> Glu | N/A | missense |
| rs146519482, CM004810 | 168 | Glu - > Gln | hemochromatosis | missense |
| CM004106 | 168 | Glu -> Term | hemochromatosis | nonsense |
| CM004107 | 169 | Trp -> Term | hemochromatosis | nonsense |
| CM015326 | 176 | Ala -> Val | hemochromatosis | missense |
| rs199916850, CM081301 | 183 | Leu -> Pro | hemochromatosis | missense |
| rs140957442 | 192 | Gln -> Term | N/A | nonsense |
| rs4986950 | 217 | Thr -> Ile | N/A | missense |
| rs144797937 | 224 | Arg -> Trp | N/A | missense |
| rs62625346, CM034097 | 224 | Arg -> Gln | hemochromatosis | missense |
| CM101181 | 233 | Gln -> Term | hemochromatosis | nonsense |
| rs140515012 | 245 | Pro -> Ala | N/A | missense |
| rs150402693 | 251 | Phe -> Leu | N/A | missense |
| rs138176635 | 252 | E -> G | N/A | missense |
| rs182920795 | 253 | Pro -> Pro | N/A | synonymous |
| rs202068193 | 256 | Val -> Ile | N/A | missense |
| rs143846467 | 259 | Asn -> Ser | N/A | missense |
| CM024530 | 272 | Val -> Leu | hemochromatosis | missense |
| rs140080192, CM994771 | 277 | Glu -> Lys | hemochromatosis | missense |
| rs369354634 | 281 | Thr -> Thr | N/A | synonymous |
| rs1800562, CM960828 | 282 | Cys -> Tyr | hemochromatosis | missense |
| CM004391 | 282 | Cys -> Ser | hemochromatosis | missense |
| rs111033563, CM032271 | 283 | Gln-Pro | hemochromatosis (SwissVar) | missense |
| rs201310322 | 292 | Pro -> Pro | N/A | synonymous |
| rs143175221, HM030028 | 295 | Val -> Ala | hemochromatosis (SwissVar) | missense |
| rs114038675 | 298 | Glu -> Glu | N/A | synonymous |
| rs372856303 | 301 | Pro -> Pro | N/A | synonymous |
| rs147519426 | 315 | Val -> Gly | N/A | missense |
| rs148632352 | 315 | Val -> Val | N/A | synonymous |
| rs371192232 | 317 | Val -> Val | N/A | synonymous |
| rs141229562 | 318 | Val -> Ile | N/A | missense |
| rs150716212 | 322 | Ile -> Thr | N/A | missense |
| rs138993448 | 327 | Ile -> Thr | N/A | missense |
| rs111033558, CM990722 | 330 | Arg -> Met | hemochromatosis (SwissVar). In hereditary haemochromatosis (HH) (PMD) | missense |
| rs368122334 | 340 | Gly -> Ala | N/A | missense |
| rs35201683 | 342 | Tyr -> Tyr | N/A | synonymous |
| rs370285936 | 343 | Val -> Asp | N/A | missense |
| rs146508927 | 347 | Arg -> His | N/A | missense |
</figtable>
