Difference between revisions of "Task 7 (MSUD)"

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m (Mutations of BCKDHA)
m (Mutation map)
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== Mutation map ==
 
== Mutation map ==
  +
  +
Following table contains the SNPs that we have chosen from different databases:
  +
{| class='wikitable' border='1'
  +
! Accession.Number.Codon.number.Pathogenic.Mutation.Type
  +
|-
  +
| 29 N/A G29E missense
  +
|-
  +
| rs11549936 38 N/A P38H missense
  +
|-
  +
| rs150177278 41 N/A Q41R missense
  +
|-
  +
| 59 N/A A59V missense
  +
|-
  +
| 62 N/A I62M missense
  +
|-
  +
| CM093772 69 Maple syrup urine disease Q69* nonsense
  +
|-
  +
| 71 N/A N71S missense
  +
|-
  +
| 82 N/A M82I missense
  +
|-
  +
| rs148571328 95 N/A H95H synonymous-codon
  +
|-
  +
| CM005526 109 Maple syrup urine disease M109T missense
  +
|-
  +
| rs150700696 111 N/A L111L synonymous-codon
  +
|-
  +
| CM021496 125 Maple syrup urine disease Q125E missense
  +
|-
  +
| 127 N/A R127W missense
  +
|-
  +
| rs146804716 140 N/A H140H synonymous-codon
  +
|-
  +
| rs34442879 150 N/A T150M missense
  +
|-
  +
| CM021497 151 Maple syrup urine disease T151M missense
  +
|-
  +
| CM082498 152 Maple syrup urine disease D152N missense
  +
|-
  +
| CM930067 159 Maple syrup urine disease R159W missense
  +
|-
  +
| 159 N/A R159A missense
  +
|-
  +
| 159 maple syrup urine disease type ia (SwissVar) R159W missense
  +
|-
  +
| CM984173 166 Maple syrup urine disease Y166N missense
  +
|-
  +
| CM984174 167 Maple syrup urine disease R167Q missense
  +
|-
  +
| CM930068 190 Maple syrup urine disease Q190K missense
  +
|-
  +
| 190 maple syrup urine disease type ia (SwissVar) Q190K missense
  +
|-
  +
| rs190610188 199 N/A R199C missense
  +
|-
  +
| 6 204 MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA G204S missense
  +
|-
  +
| 209 N/A L209A missense
  +
|-
  +
| CM097509 211 Maple syrup urine disease T211M missense
  +
|-
  +
| CM984175 213 Maple syrup urine disease I213T missense
  +
|-
  +
| rs114716391 215 N/A A215A synonymous-codon
  +
|-
  +
| CM062450 216 Maple syrup urine disease A216V missense
  +
|-
  +
| 8 219 MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA C219W missense
  +
|-
  +
| 5 220 MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA R220W missense
  +
|-
  +
| CM062451 220 Maple syrup urine disease A220V missense
  +
|-
  +
| 222 N/A A222T missense
  +
|-
  +
| 244 N/A G244R missense
  +
|-
  +
| 3 245 MAPLE SYRUP URINE DISEASE, INTERMEDIATE, TYPE IA G245R missense
  +
|-
  +
| rs137852874 248 True G248S missense
  +
|-
  +
| CM984176 249 Maple syrup urine disease G249S missense
  +
|-
  +
| rs199599175 252 N/A A252T missense
  +
|-
  +
| CM930069 253 Maple syrup urine disease A253T missense
  +
|-
  +
| 253 maple syrup urine disease type ia (SwissVar) A253T missense
  +
|-
  +
| CM005527 254 Maple syrup urine disease A254D missense
  +
|-
  +
| CM021498 258 Maple syrup urine disease C258Y missense
  +
|-
  +
| rs137852876 263 True C263W missense
  +
|-
  +
| CM045934 264 Maple syrup urine disease C264W missense
  +
|-
  +
| 264 N/A C264W missense
  +
|-
  +
| rs137852873 264 True R264W missense
  +
|-
  +
| 7 265 MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA T265R missense
  +
|-
  +
| CM984177 265 Maple syrup urine disease R265W missense
  +
|-
  +
| 265 N/A R265W missense
  +
|-
  +
| CM984178 267 Maple syrup urine disease N267S missense
  +
|-
  +
| rs61737367 279 N/A R279R synonymous-codon
  +
|-
  +
| CM062452 283 Maple syrup urine disease G283D missense
  +
|-
  +
| CM984179 285 Maple syrup urine disease A285P missense
  +
|-
  +
| CM970163 287 Maple syrup urine disease R287* nonsense
  +
|-
  +
| rs137852871 289 True G289R missense
  +
|-
  +
| CM950135 290 Maple syrup urine disease G290R missense
  +
|-
  +
| 290 maple syrup urine disease type ia (SwissVar) G290R missense
  +
|-
  +
| 296 N/A R296C missense
  +
|-
  +
| CM062446 297 Maple syrup urine disease R297C missense
  +
|-
  +
| CM076017 297 Maple syrup urine disease R297H missense
  +
|-
  +
| CM062453 300 Maple syrup urine disease G300S missense
  +
|-
  +
| CM062449 302 Maple syrup urine disease D302A missense
  +
|-
  +
| rs139390622 306 N/A N306N synonymous-codon
  +
|-
  +
| 309 N/A T309R missense
  +
|-
  +
| rs137852875 309 True T309R missense
  +
|-
  +
| CM984180 310 Maple syrup urine disease T310R missense
  +
|-
  +
| CM034725 314 Maple syrup urine disease R314* missense
  +
|-
  +
| rs201109190 314 N/A R314Q missense
  +
|-
  +
| rs284652 323 N/A F323F synonymous-codon
  +
|-
  +
| CM930070 326 Maple syrup urine disease I326T missense
  +
|-
  +
| 326 maple syrup urine disease type ia (SwissVar) I326T missense
  +
|-
  +
| CM062447 327 Maple syrup urine disease E327K missense
  +
|-
  +
| CM076018 328 Maple syrup urine disease A328T missense
  +
|-
  +
| rs146300600 343 N/A A343V missense
  +
|-
  +
| 345 N/A R345C missense
  +
|-
  +
| CM062448 346 Maple syrup urine disease R346H missense
  +
|-
  +
| rs144276456 346 N/A S346S synonymous-codon
  +
|-
  +
| 356 N/A Q356R missense
  +
|-
  +
| 361 N/A I361V missense
  +
|-
  +
| CM984181 363 Maple syrup urine disease R363W missense
  +
|-
  +
| 4 364 MAPLE SYRUP URINE DISEASE, INTERMEDIATE, TYPE IA. MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA, INCLUDED F364C missense
  +
|-
  +
| 1 393 MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA Y393N missense
  +
|-
  +
| 398 N/A E398K missense
  +
|-
  +
| rs145595627 401 N/A P401P synonymous-codon
  +
|-
  +
| 403 N/A N403S missense
  +
|-
  +
| rs137852872 407 True F407C missense
  +
|-
  +
| 408 N/A F408C missense
  +
|-
  +
| CM950136 409 Maple syrup urine disease F409C missense
  +
|-
  +
| 409 maple syrup urine disease type ia (SwissVar) F409C missense
  +
|-
  +
| CM032853 412 Maple syrup urine disease V412M missense
  +
|-
  +
| CM082499 413 Maple syrup urine disease Y413H missense
  +
|-
  +
| CM940169 413 Maple syrup urine disease Y413C missense
  +
|-
  +
| 413 maple syrup urine disease type ia (SwissVar) Y413C missense
  +
|-
  +
| rs141991700 422 N/A Q422K missense
  +
|-
  +
| 428 N/A R428H missense
  +
|-
  +
| rs137852870 436 True Y436N missense
  +
|-
  +
| CM890022 438 Maple syrup urine disease Y438N missense
  +
|-
  +
| 438 maple syrup urine disease type ia (SwissVar) Y438N missense
  +
|}
   
 
== Discussion ==
 
== Discussion ==

Revision as of 21:53, 23 June 2013

HGMD

Database facts

Q: What information is given?

A: Only disease causing mutations are included. HGMD lists the following mutation types:

  • missense/nonsense
  • splicing
  • regulatory
  • small deletions
  • small insertions
  • small indels
  • gross deletions
  • gross insertions/duplications
  • complex rearrangements
  • repeat variations

For each mutation entry the following information is given in the public version:

  • accession number
  • codon change
  • amino acid change
  • codon number
  • phenotype
  • reference
  • comments

Q: How recent is the release?

A: Release 2013.1 is the current professional version. Entries are made publicly accessible three years after they are included. Mutations that are taken from publicly available locus-specific mutation databases are immediately added to the public version.

Q: Where does the information come from?

A: The information is extracted from articles that describe genetic diseases. So only published mutations are included.

Mutations of BCKDHA

The following mutations are listed for BCKDHA (20 June 2013):

mutation type number of mutations
missense/nonsense 40
splicing 2
small deletions 4
small insertions 1
small indels 1
gross deletions 2
complex rearrangements 1


All reported mutations are associated with MSUD. Among the 40 mutations of category "missense/nonsense", there are only missense mutations listet and no nonsense mutations.

Definition of the mutation types:

  • missense: single base substitution that leads to amino acid change
  • nonsense: single base substitution that leads to a stop codon
  • splicing: mutation that affects a splicing side
  • small deletion: deletion of few base pairs
  • small insertion: insertion of few base pairs
  • small indel: insertion / deletion of few base pairs
  • gross deletion: deletion of many base pairs
  • complex rearrangement: insertion / deletion of many base pairs

dbSNP

Histogram of different types of SNPs reported in dbSNP.

Database facts

Q: What information is given?

A: Short variations in nucleotide sequence from many different organisms. It contains following information:

  • mutations of different categories:
    • single nucleotide variations
    • indels
    • short tandem repeats
    • microsatellites
  • additional information for rare variations
    • disease relationship
    • genotype information
    • allele origin
    • somatic or germline events

Q: How recent is the release?

A: Current version of dbSNP is build 137. dbSNP web query, ftp data and Entrez Indexing were released on Jun 26, 2012. New release of BLAST database is not yet done. The newest release of BLAST database was released on Nov 14, 2011 from build 135.

Q: Where does the information come from?

A: dbSNP is created by the cooperation of the National Human Genome Research Institute and the National Center for Biotechnology Information. It is integrated with the NCBI Genomic data. There are two sorts of content in dbSNP: submitted and computed data. During a build cycle, submitted SNPs (identified by ss#) which map to the same genomic position, are clustered to a non-redundant set of reference SNPs (refSNPs), that get a unique rs# identifier.

Mutations of BCKDHA

Totally 292 SNPs in coding region of BCKDHA were found in dbSNP. 4 mutations are nonsense (stop-gained) which introduce stop condon in the coding region. 152 mutations are missense among which 28 mutations can cause disease. 136 mutations are synonymous codons.

SNPdbe

Database facts

Q: What information is given?

A: Experimentally annotated effects of non-synonymous SNPs (nsSNP). Computationally annotated structural and functional effects of nsSNP. Association between nsSNP and diseases.

Q: How recent is the release?

A: The most recent update took place on Mar 05, 2012.

Q: Where does the information come from?

A: Experimentally annotated nsSNP from dbSNP; Variants from UniProt and PMD; Genomic data from 1000 Genome collection; predicted impacts on protein structure and function are computed with SNAP and SIFT.

Mutations of BCKDHA

102 SNPs were reported in SNPdbe for BCKDHA. Among them 8 SNPs were reported to have association to MSUD.

OMIM

Database facts

Q: What information is given?

A: In the allelic variants section of a gene entry, mutations (e. g. substitions or deletions) are given and the phenotype that they are causing. Only selected mutations are listed (see OMIM FAQ), most of which are disease associated.

Q: How recent is the release?

A: OMIM is updated daily. The entry for BCKDHA was last updated 05/23/2012.

Q: Where does the information come from?

A: The information comes from published articles. For each mutation the reference article is given in the text of the allelic variants section.

Mutations of BCKDHA

For BCKDHA, there are 7 missense mutations listed and 2 deletions, where one is a 1-bp (base pair) deletion and the other 8-bp (last update of entry: 05/23/2012). All these mutations are associated with MSUD type IA (classic or intermediate form).

SNPedia

Database facts

Q: What information is given?

A: The wiki style project 'SNPedia' is open to the internet community. It contains information about effects of SNPs. Annotations from wide range of internet resources such as the dbSNP project, Ensembl or even google search are included into SNPedia. It tries to gather all SNP related information to one web site.

Q: How recent is the release?

A: Due to contribution of its user community, new updates could occur at any time point. But still it depends on the release of other SNP related resources.

Q: Where does the information come from?

A: Many different public available databases, resources about SNPs, publications about genomic studies.

Mutations of BCKDHA

Due the fact that SNPedia is not a database-like data source. Statistics over reported SNPs for BCKDHA is hard to obtain.

Mutation map

Following table contains the SNPs that we have chosen from different databases:

Accession.Number.Codon.number.Pathogenic.Mutation.Type
29 N/A G29E missense
rs11549936 38 N/A P38H missense
rs150177278 41 N/A Q41R missense
59 N/A A59V missense
62 N/A I62M missense
CM093772 69 Maple syrup urine disease Q69* nonsense
71 N/A N71S missense
82 N/A M82I missense
rs148571328 95 N/A H95H synonymous-codon
CM005526 109 Maple syrup urine disease M109T missense
rs150700696 111 N/A L111L synonymous-codon
CM021496 125 Maple syrup urine disease Q125E missense
127 N/A R127W missense
rs146804716 140 N/A H140H synonymous-codon
rs34442879 150 N/A T150M missense
CM021497 151 Maple syrup urine disease T151M missense
CM082498 152 Maple syrup urine disease D152N missense
CM930067 159 Maple syrup urine disease R159W missense
159 N/A R159A missense
159 maple syrup urine disease type ia (SwissVar) R159W missense
CM984173 166 Maple syrup urine disease Y166N missense
CM984174 167 Maple syrup urine disease R167Q missense
CM930068 190 Maple syrup urine disease Q190K missense
190 maple syrup urine disease type ia (SwissVar) Q190K missense
rs190610188 199 N/A R199C missense
6 204 MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA G204S missense
209 N/A L209A missense
CM097509 211 Maple syrup urine disease T211M missense
CM984175 213 Maple syrup urine disease I213T missense
rs114716391 215 N/A A215A synonymous-codon
CM062450 216 Maple syrup urine disease A216V missense
8 219 MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA C219W missense
5 220 MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA R220W missense
CM062451 220 Maple syrup urine disease A220V missense
222 N/A A222T missense
244 N/A G244R missense
3 245 MAPLE SYRUP URINE DISEASE, INTERMEDIATE, TYPE IA G245R missense
rs137852874 248 True G248S missense
CM984176 249 Maple syrup urine disease G249S missense
rs199599175 252 N/A A252T missense
CM930069 253 Maple syrup urine disease A253T missense
253 maple syrup urine disease type ia (SwissVar) A253T missense
CM005527 254 Maple syrup urine disease A254D missense
CM021498 258 Maple syrup urine disease C258Y missense
rs137852876 263 True C263W missense
CM045934 264 Maple syrup urine disease C264W missense
264 N/A C264W missense
rs137852873 264 True R264W missense
7 265 MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA T265R missense
CM984177 265 Maple syrup urine disease R265W missense
265 N/A R265W missense
CM984178 267 Maple syrup urine disease N267S missense
rs61737367 279 N/A R279R synonymous-codon
CM062452 283 Maple syrup urine disease G283D missense
CM984179 285 Maple syrup urine disease A285P missense
CM970163 287 Maple syrup urine disease R287* nonsense
rs137852871 289 True G289R missense
CM950135 290 Maple syrup urine disease G290R missense
290 maple syrup urine disease type ia (SwissVar) G290R missense
296 N/A R296C missense
CM062446 297 Maple syrup urine disease R297C missense
CM076017 297 Maple syrup urine disease R297H missense
CM062453 300 Maple syrup urine disease G300S missense
CM062449 302 Maple syrup urine disease D302A missense
rs139390622 306 N/A N306N synonymous-codon
309 N/A T309R missense
rs137852875 309 True T309R missense
CM984180 310 Maple syrup urine disease T310R missense
CM034725 314 Maple syrup urine disease R314* missense
rs201109190 314 N/A R314Q missense
rs284652 323 N/A F323F synonymous-codon
CM930070 326 Maple syrup urine disease I326T missense
326 maple syrup urine disease type ia (SwissVar) I326T missense
CM062447 327 Maple syrup urine disease E327K missense
CM076018 328 Maple syrup urine disease A328T missense
rs146300600 343 N/A A343V missense
345 N/A R345C missense
CM062448 346 Maple syrup urine disease R346H missense
rs144276456 346 N/A S346S synonymous-codon
356 N/A Q356R missense
361 N/A I361V missense
CM984181 363 Maple syrup urine disease R363W missense
4 364 MAPLE SYRUP URINE DISEASE, INTERMEDIATE, TYPE IA. MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA, INCLUDED F364C missense
1 393 MAPLE SYRUP URINE DISEASE, CLASSIC, TYPE IA Y393N missense
398 N/A E398K missense
rs145595627 401 N/A P401P synonymous-codon
403 N/A N403S missense
rs137852872 407 True F407C missense
408 N/A F408C missense
CM950136 409 Maple syrup urine disease F409C missense
409 maple syrup urine disease type ia (SwissVar) F409C missense
CM032853 412 Maple syrup urine disease V412M missense
CM082499 413 Maple syrup urine disease Y413H missense
CM940169 413 Maple syrup urine disease Y413C missense
413 maple syrup urine disease type ia (SwissVar) Y413C missense
rs141991700 422 N/A Q422K missense
428 N/A R428H missense
rs137852870 436 True Y436N missense
CM890022 438 Maple syrup urine disease Y438N missense
438 maple syrup urine disease type ia (SwissVar) Y438N missense

Discussion

References

  • Online Mendelian Inheritance in Man, OMIM®. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD), 2013. OMIM
  • Stenson et al (2003). The Human Gene Mutation Database (HGMD®): 2003 Update. Hum Mutat(2003) 21:577-581. HGMD
  • Kitts A, Sherry S. The Single Nucleotide Polymorphism Database (dbSNP) of Nucleotide Sequence Variation. 2002 Oct 9 [Updated 2011 Feb 2]. In: McEntyre J, Ostell J, editors. The NCBI Handbook [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2002-. Chapter 5. Available from: http://www.ncbi.nlm.nih.gov/books/NBK21088/
  • dbSNP
  • Schaefer C, Meier A, Rost B, Bromberg Y (2012). SNPdbe: Constructing an nsSNP functional impacts database. Bioinformatics; 28(4):601-602. SNPdbe
  • Cariaso M, Lennon G. SNPedia: a wiki supporting personal genome annotation, interpretation and analysis. Nucleic Acids Research 2011; doi: 10.1093/nar/gkr798. SNPedia