Difference between revisions of "Task 7: Research SNPs"

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(Databases comparison)
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All found synonymous SNPS in coding region of the isoform 1 human and the transcript variant 1 of the HFE gene are listed in <xr id="dbSNP silent"/>.
 
All found synonymous SNPS in coding region of the isoform 1 human and the transcript variant 1 of the HFE gene are listed in <xr id="dbSNP silent"/>.
  +
  +
  +
<figtable id="dbSNP all">
  +
{| class="colBasic2"
  +
!dbSNP rs cluster ID || Function || mRNA pos. || codon pos || nucleotide change || aa pos || aa change
  +
|-
  +
rs149342416 || missense || 178 || 3 || G -> C || 6 || Arg -> Ser
  +
|-
  +
rs114758821 || synonymous || 181 || 3 || G -> A || 7 || Pro -> Pro
  +
|-
  +
rs368895240 || synonymous || 190 || 3 || C -> T || 10 || Leu -> Leu
  +
|-
  +
rs201657128 || missense || 200 || 1 || C -> G || 14 || Leu -> Val
  +
|-
  +
rs143662783 || missense || 210 || 2 || C -> T || 17 || Thr -> Ile
  +
|-
  +
rs148161858 || missense || 228 || 2 || G -> A || 23 || Arg -> His
  +
|-
  +
rs2242956 || missense || 264 || 2 || T -> C || 35 || Met -> Thr
  +
|-
  +
rs377254261 || missense || 270 || 2 || C -> T || 37 || Ala -> Val
  +
|-
  +
rs147297176 || synonymous || 334 || 3 || C -> T || 58 || Phe -> Phe
  +
|-
  +
rs147426902 || synonymous || 349 || 3 || T -> C || 63 || His -> His
  +
|-
  +
rs139523708 || missense || 360 || 2 || G -> A || 67 || Arg -> His
  +
|-
  +
rs62625342 || synonymous || 388 || 3 || C -> T || 76 || Ser -> Ser
  +
|-
  +
rs376650371 || missense || 451 || 3 || G -> A || 97 || Met -> Ile
  +
|-
  +
rs199988202 || missense || 477 || 2 || T -> C || 106 || Met -> Thr
  +
|-
  +
rs200706856 || missense || 545 || 1 || G -> A || 129 || Asp -> Asn
  +
|-
  +
rs201885016 || missense || 549 || 2 || A -> G || 130 || Asn -> Ser
  +
|-
  +
rs369790080 || synonymous || 556 || 3 || C -> T || 132 || Thr -> Thr
  +
|-
  +
rs372789940 || missense || 581 || 1 || G -> A || 141 || Asp -> Asn
  +
|-
  +
rs199879669 || missense || 629 || 1 || G -> C || 157 || Ala -> Pro
  +
|-
  +
rs145475682 || missense || 644 || 1 || G -> T || 162 || Ala -> Ser
  +
|-
  +
rs148480830 || synonymous || 646 || 3 || C -> G || 162 || Ala -> Ala
  +
|-
  +
rs144170531 || missense || 656 || 1 || A -> G || 166 || Lys -> Glu
  +
|-
  +
rs146519482 || missense || 662 || 1 || G -> C || 168 || Glu -> Gln
  +
|-
  +
rs199916850 || missense || 708 || 2 || T -> C || 183 || Leu -> Pro
  +
|-
  +
rs140957442 || nonsense || 734 || 1 || C -> T || 192 || Gln -> [Te
  +
|-
  +
rs4986950 || missense || 810 || 2 || C -> T || 217 || Thr -> Ile
  +
|-
  +
rs144797937 || missense || 830 || 1 || C -> T || 224 || Arg -> Trp
  +
|-
  +
rs62625346 || missense || 831 || 2 || G -> A || 224 || Arg -> Gln
  +
|-
  +
rs140515012 || missense || 893 || 1 || C -> G || 245 || Pro -> Ala
  +
|-
  +
rs150402693 || missense || 913 || 3 || C -> A || 251 || Phe -> Leu
  +
|-
  +
rs182920795 || synonymous || 919 || 3 || T -> A || 253 || Pro -> Pro
  +
|-
  +
rs202068193 || missense || 926 || 1 || G -> A || 256 || Val -> Ile
  +
|-
  +
rs143846467 || missense || 936 || 2 || A -> G || 259 || Asn -> Ser
  +
|-
  +
rs140080192 || missense || 989 || 1 || G -> A || 277 || Glu -> Lys
  +
|-
  +
rs369354634 || synonymous || 1003 || 3 || G -> A || 281 || Thr -> Thr
  +
|-
  +
rs201310322 || synonymous || 1036 || 3 || C -> T || 292 || Pro -> Pro
  +
|-
  +
rs143175221 || missense || 1044 || 2 || T -> C || 295 || Val -> Ala
  +
|-
  +
rs114038675 || synonymous || 1054 || 3 || G -> A || 298 || Glu -> Glu
  +
|-
  +
rs372856303 || synonymous || 1063 || 3 || G -> A || 301 || Pro -> Pro
  +
|-
  +
rs147519426 || missense || 1104 || 2 || T -> G || 315 || Val -> Gly
  +
|-
  +
rs148632352 || synonymous || 1105 || 3 || T -> C || 315 || Val -> Val
  +
|-
  +
rs371192232 || synonymous || 1111 || 3 || C -> T || 317 || Val -> Val
  +
|-
  +
rs141229562 || missense || 1112 || 1 || G -> A || 318 || Val -> Ile
  +
|-
  +
rs150716212 || missense || 1125 || 2 || T -> C || 322 || Ile -> Thr
  +
|-
  +
rs138993448 || missense || 1140 || 2 || T -> C || 327 || Ile -> Thr
  +
|-
  +
rs368122334 || missense || 1179 || 2 || G -> C || 340 || Gly -> Ala
  +
|-
  +
rs35201683 || synonymous || 1186 || 3 || C -> T || 342 || Tyr -> Tyr
  +
|-
  +
rs370285936 || missense || 1188 || 2 || T -> A || 343 || Val -> Asp
  +
|-
  +
rs146508927 || missense || 1200 || 2 || G -> A || 347 || Arg -> His
  +
|-
  +
|+ style="caption-side: bottom; text-align: left" |<font size=2>'''Table 3:''' Synonymous SNPS in the coding regin of the isoform 1 human and the transcript variant 1 of the HFE gene.
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|}
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</figtable>
   
   

Revision as of 17:26, 14 August 2013

Lab journal Task 7

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HGMD (The Human Gene Mutation Database)

The search results for the HFE gene contain the different types of mutations that are specified in <xr id="hgmd"/>:

<figtable id="hgmd">

mutation type definition number
missense, nonsense mutation that leads to a change of amino acid or a stop codon 28
splicing mutation that affects mRNA splicing 3
regulatory substitiution causing abnormal regulation 1
small deletion micro deletion (<= 20 bp) 4
small insertion micro insertions (<= 20 bp) 1
small indel micro indels (<= 20 bp) 0
gross deletion delition > 20 bp 2
gross insertions/duplications insertion > 20bp 0
complex rearrangments rearrangements of stretches of the DNA sequence 1
repeat variations differences in repeat length 0
Table 1: Table of the different mutation types that were found for HFE in the HGMD.

</figtable>

In total, we found 40 mutation in the public version of the database and 49 in the non-public version.

<figtable id="hgmd missense">

accession number codon change aa change codon number
CM032270 AGGc-AGC Arg-Ser 6
CM091838 TTG-TGG Leu-Trp 46
CM994469 cGTG-ATG Val-Met 53
CM994470 cGTG-ATG Val-Met 59
HM971246 CATg-CAC His-His 63
CM960827 tCAT-GAT His-Asp 63
CM990718 gAGT-TGT Ser-Cys 65
CM033969 tCGC-TGC Arg-Cys 66
CM020721 cCGA-TGA Arg-Term 71
CM990719 aGGG-CGG Gly-Arg 93
CM990720 ATT-ACT Ile-Thr 105
CM990721 CAAg-CAC Gln-His 127
CM091839 aGAC-AAC Asp-Asn 129
CM091840 TACg-TAG Tyr-Term 138
CM004810 gGAG-CAG Glu-Gln 168
CM004106 gGAG-TAG Glu-Term 168
CM004107 TGG-TAG Trp-Term 169
CM015326 GCC-GTC Ala-Val 176
CM081301 CTG-CCG Leu-Pro 183
CM034097 CGG-CAG Arg-Gln 224
CM101181 cCAG-TAG Gln-Term 233
CM024530 tGTA-TTA Val-Leu 272
CM994771 aGAG-AAG Glu-Lys 277
CM960828 TGC-TAC
CM004391 TGC-TCC Cys-Ser 282
CM032271 CAG-CCG Gln-Pro 283
HM030028 GTG-GCG Val-Ala 295
CM990722 AGG-ATG Arg-Met 330
Table 2: 28 missense and nonsense mutations for HFE from the HGMD.

</figtable>

The 28 missense and nonsense mutations for HFE are listed in <xr id="hgmd missense"/> together with the amino acid (aa) change and the codon number.

dbSNP

dbSNP was searched to silent (synonymous) mutations of the HFE gene. Silent mutations are mutations in the nucleotide sequence that do not lead to a change in the amino acid sequence of the protein.

<figtable id="dbSNP silent">

cluster ID MAF SNP allel residue codon position aa position
rs114758821 9E-4 G -> A Pro 3 7
rs147297176 5E-4 C -> T Phe 3 58
rs147426902 3.2E-3 T -> C His 3 63
rs62625342 5E-4 C -> T Ser 3 76
rs148480830 - C -> G Ala 3 162
rs182920795 5E-4 T -> A Pro 3 253
rs201310322 - C -> T Pro 3 292
rs114038675 5E-4 G -> A Glu 3 298
rs148632352 - T -> C Val 3 315
rs35201683 6.4E-3 C -> T Tyr 3 342
Table 3: Synonymous SNPS in the coding regin of the isoform 1 human and the transcript variant 1 of the HFE gene.

</figtable>

All found synonymous SNPS in coding region of the isoform 1 human and the transcript variant 1 of the HFE gene are listed in <xr id="dbSNP silent"/>.


<figtable id="dbSNP all">

rs149342416 || missense || 178 || 3 || G -> C || 6 || Arg -> Ser rs114758821 || synonymous || 181 || 3 || G -> A || 7 || Pro -> Pro rs368895240 || synonymous || 190 || 3 || C -> T || 10 || Leu -> Leu rs201657128 || missense || 200 || 1 || C -> G || 14 || Leu -> Val rs143662783 || missense || 210 || 2 || C -> T || 17 || Thr -> Ile rs148161858 || missense || 228 || 2 || G -> A || 23 || Arg -> His rs2242956 || missense || 264 || 2 || T -> C || 35 || Met -> Thr rs377254261 || missense || 270 || 2 || C -> T || 37 || Ala -> Val rs147297176 || synonymous || 334 || 3 || C -> T || 58 || Phe -> Phe rs147426902 || synonymous || 349 || 3 || T -> C || 63 || His -> His rs139523708 || missense || 360 || 2 || G -> A || 67 || Arg -> His rs62625342 || synonymous || 388 || 3 || C -> T || 76 || Ser -> Ser rs376650371 || missense || 451 || 3 || G -> A || 97 || Met -> Ile rs199988202 || missense || 477 || 2 || T -> C || 106 || Met -> Thr rs200706856 || missense || 545 || 1 || G -> A || 129 || Asp -> Asn rs201885016 || missense || 549 || 2 || A -> G || 130 || Asn -> Ser rs369790080 || synonymous || 556 || 3 || C -> T || 132 || Thr -> Thr rs372789940 || missense || 581 || 1 || G -> A || 141 || Asp -> Asn rs199879669 || missense || 629 || 1 || G -> C || 157 || Ala -> Pro rs145475682 || missense || 644 || 1 || G -> T || 162 || Ala -> Ser rs148480830 || synonymous || 646 || 3 || C -> G || 162 || Ala -> Ala rs144170531 || missense || 656 || 1 || A -> G || 166 || Lys -> Glu rs146519482 || missense || 662 || 1 || G -> C || 168 || Glu -> Gln rs199916850 || missense || 708 || 2 || T -> C || 183 || Leu -> Pro rs140957442 || nonsense || 734 || 1 || C -> T || 192 || Gln -> [Te rs4986950 || missense || 810 || 2 || C -> T || 217 || Thr -> Ile rs144797937 || missense || 830 || 1 || C -> T || 224 || Arg -> Trp rs62625346 || missense || 831 || 2 || G -> A || 224 || Arg -> Gln rs140515012 || missense || 893 || 1 || C -> G || 245 || Pro -> Ala rs150402693 || missense || 913 || 3 || C -> A || 251 || Phe -> Leu rs182920795 || synonymous || 919 || 3 || T -> A || 253 || Pro -> Pro rs202068193 || missense || 926 || 1 || G -> A || 256 || Val -> Ile rs143846467 || missense || 936 || 2 || A -> G || 259 || Asn -> Ser rs140080192 || missense || 989 || 1 || G -> A || 277 || Glu -> Lys rs369354634 || synonymous || 1003 || 3 || G -> A || 281 || Thr -> Thr rs201310322 || synonymous || 1036 || 3 || C -> T || 292 || Pro -> Pro rs143175221 || missense || 1044 || 2 || T -> C || 295 || Val -> Ala rs114038675 || synonymous || 1054 || 3 || G -> A || 298 || Glu -> Glu rs372856303 || synonymous || 1063 || 3 || G -> A || 301 || Pro -> Pro rs147519426 || missense || 1104 || 2 || T -> G || 315 || Val -> Gly rs148632352 || synonymous || 1105 || 3 || T -> C || 315 || Val -> Val rs371192232 || synonymous || 1111 || 3 || C -> T || 317 || Val -> Val rs141229562 || missense || 1112 || 1 || G -> A || 318 || Val -> Ile rs150716212 || missense || 1125 || 2 || T -> C || 322 || Ile -> Thr rs138993448 || missense || 1140 || 2 || T -> C || 327 || Ile -> Thr rs368122334 || missense || 1179 || 2 || G -> C || 340 || Gly -> Ala rs35201683 || synonymous || 1186 || 3 || C -> T || 342 || Tyr -> Tyr rs370285936 || missense || 1188 || 2 || T -> A || 343 || Val -> Asp rs146508927 || missense || 1200 || 2 || G -> A || 347 || Arg -> His
dbSNP rs cluster ID Function mRNA pos. codon pos nucleotide change aa pos aa change
Table 3: Synonymous SNPS in the coding regin of the isoform 1 human and the transcript variant 1 of the HFE gene.

</figtable>


SNPdbe

35 mutations that are associated with the human HFE protein were found in SNPdbe.


<figtable id="exp evidence">

exp. evidence count
1000Genome,freq,cluster 6
by cluster 6
by cluster,freq 2
Not validated 13
by freq 8
Table 4: Types of experimental evidence and their occurence among the 35 mutations associated with HFE.

</figtable>

Not all mutations have experimental evidence, over one third is not validated, see <xr id="exp evidence"/>.

<figtable id="snpdbe">

dbSNP Mutation Disease association Experimental evidence
rs1799945 H63D In hereditary haemochromatosis (HH) (PMD) 1000Genome,freq,cluster
rs1800562 C282Y hemochromatosis (SwissVar) 1000Genome,freq,cluster
rs1800730 S65C hemochromatosis (SwissVar). In hereditary hemochromatosis patient who had resulted positive to screening for iron overload (PMD) 1000Genome,freq,cluster
rs2242956 M35T N/A by cluster
rs4986950 T217I N/A by cluster,freq
rs28934595 Q127H hemochromatosis (SwissVar). In variegate porphyria (VP) (PMD) by cluster
rs28934596 I105T hemochromatosis (SwissVar). In hemochromatosis (PMD) by cluster
rs28934597 G93R hemochromatosis (SwissVar). In hemochromatosis (PMD) by cluster
rs28934889 V53M N/A 1000Genome,freq,cluster
rs62625346 R224Q N/A by cluster,freq
rs28934890 V59M N/A Not validated
rs111033558 R330M hemochromatosis (SwissVar). In hereditary haemochromatosis (HH) (PMD) by cluster
rs111033563 Q283P hemochromatosis (SwissVar) by cluster
rs149342416 R6S hemochromatosis (SwissVar) by freq
rs140080192 E277K N/A 1000Genome,freq,cluster
rs143175221 V295A hemochromatosis (SwissVar) by freq
rs148161858 R23H N/A 1000Genome,freq,cluster
N/A M106T N/A Not validated
rs146519482 E168Q N/A Not validated
N/A L183P N/A Not validated
rs138176635 E252G N/A Not validated
rs138993448 I327T N/A Not validated
rs139523708 R67H N/A Not validated
rs140515012 P245A N/A Not validated
rs141229562 V318I N/A Not validated
rs143662783 T17I N/A by freq
rs143846467 N259S N/A Not validated
rs144170531 K166E N/A by freq
rs144797937 R224W N/A by freq
rs145475682 A162S N/A by freq
rs146508927 R347H N/A by freq
rs147519426 V315G N/A by freq
rs149662565 P160T N/A Not validated
rs150402693 F251L N/A Not validated
rs150716212 I322T N/A Not validated
Table 4: Mutations in the HFE protein from SNPdbe.

</figtable>

A list of the 35 mutations and their experimental evidence can be found in <xr id="snpdbe"/>.

OMIM

OMIM (Online Mendelian Inheritance in Man) also contains information about HFE, but only a small amount of all known mutations can be found.

<figtable id="omim">

dbSNP accession Phenotype Mutation
rs1799945 HEMOCHROMATOSIS HIS63ASP
rs1800730 HEMOCHROMATOSIS SER65CYS
rs28934889 HFE POLYMORPHISM VAL53MET
rs111033557 HFE POLYMORPHISM VAL59MET
rs28934595 HEMOCHROMATOSIS GLN127HIS
rs111033558 HEMOCHROMATOSIS ARG330MET
rs28934596 HEMOCHROMATOSIS ILE105THR
rs28934597 HEMOCHROMATOSIS GLY93ARG
rs111033563 HEMOCHROMATOSIS GLN283PRO
Table 5: Mutations from OMIM that are associated with the HFE protein .

</figtable>

A complete list of the mutations can be found in <xr id="omim"/>. Two of the mutations are poylmorphisms of the HFE protein and 8 of them cause the disease hemochromatosis.

Databases comparison

<figtable id="comparison">

database last update version what information where from # entries homo sapiens # HFE mutations
HGMD spring 2013 public 2013.1 (mainly 3 year old data) Collection of published gene lesions in the human genome that cause inherited diseases. Only from publications. Journals are searched manually and by computational means each week. 99869 28 missense/nonsense
dbSNP 26.06.2012 Build 137 Short nucleotide sequence variations in different organisms (common and rare) Submissions from laboratories but also private research companies. 192,678,553 10 synonymous, 41 non-synonymous, 10 disease causing SNPs and 162 SNPs in the UTR
SNPdbe 05.03.2012 - Annotations for single amino acid substitutions (SAASs), e.g. functional effect (experimental, predicted), associated disease, evol. conservation,... Based on entries from SwissProt, dbSNP, 1000 Genomes, PMD 967879 10 disease associated, 25 other
OMIM daily - Compendium of human genes, genetic phenotypes and diseases. 3,035 genes with phenotype-causing mutations known. Information from publications and databases is reviewed and summed up in texts by scientists. 21,934 2 8 disease causing mutations, 2 other
Table 6: .

</figtable>

Mutation map

References

Stenson et al (2009), The Human Gene Mutation Database (HGMD®): 2008 Update. Genome Med 1(1):13
http://www.ncbi.nlm.nih.gov/books/NBK3848/
ftp://ftp.ncbi.nih.gov/pub/factsheets/Factsheet_SNP.pdf
https://www.rostlab.org/services/snpdbe/