Difference between revisions of "Mapping SNPs BCKDHA"

From Bioinformatikpedia
(→‎SNPs in human)
(→‎SNPs in human)
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!Mutated Residue
  
!Mutated Residue
 
|-
  
|-
−
|rs137852876 || TTC || TTG || C || G || 3 || 263 || C || W
 +
|rs10853751 || TGC || TTC || C || T || 2 || 4 || T || M
 
|-
  
|-
−
|rs137852875 || TCA || TGA || C || G || 2 || 308 || T || R
 +
|rs111855817 || CGT || CAT || G || A || 2 || 28 || G || E
 
|-
  
|-
−
|rs137852874 || TAC || AAC || G || A || 1 || 248 || G || S
 +
|rs34500671 || CAG || CAG || C || G || 3 || 32 || C || W
 
|-
  
|-
−
|rs137852873 || AAC || TAC || C || T || 1 || 264 || R || W
 +
|rs34589432 || CTG || CAG || C || A || 2 || 38 || P || H
 
|-
  
|-
−
|rs137852872 || GAG || GGG || T || G || 2 || 408 || F || C
 +
|rs34442879 || GAG || GTG || C || T || 2 || 150 || T || M
 
|-
  
|-
−
|rs137852871 || ACC || ACC || G || A || 1 || 288 || G || R
 +
|rs34956071 || GGC || TGC || C || T || 1 || 169 || P || S
 
|-
  
|-
−
|rs137852870 || CAG || AAG || T || A || 1 || 437 || Y || N
 +
|rs28940288 || AGG || AGG || G || A || 1 || 243 || G || R
 
|-
  
|-
−
|rs111855817 || CGT || CAT || G || A || 2 || 28 || G || E
 +
|rs137852874 || TAC || AAC || G || A || 1 || 248 || G || S
 
|-
  
|-
−
|rs61736656 || CGC || GGC || A || G || 1 || 359 || I || V
 +
|rs137852876 || TTC || TTG || C || G || 3 || 263 || C || W
 
|-
  
|-
−
|rs34956071 || GGC || TGC || C || T || 1 || 169 || P || S
 +
|rs137852873 || AAC || TAC || C || T || 1 || 264 || R || W
 
|-
  
|-
−
|rs34589432 || CTG || CAG || C || A || 2 || 38 || P || H
 +
|rs137852871 || ACC || ACC || G || A || 1 || 288 || G || R
 
|-
  
|-
−
|rs34500671 || CAG || CAG || C || G || 3 || 32 || C || W
 +
|rs137852875 || TCA || TGA || C || G || 2 || 308 || T || R
 
|-
  
|-
−
|rs34442879 || GAG || GTG || C || T || 2 || 150 || T || M
 +
|rs61736656 || CGC || GGC || A || G || 1 || 359 || I || V
 
|-
  
|-
−
|rs28940288 || AGG || AGG || G || A || 1 || 243 || G || R
 +
|rs137852872 || GAG || GGG || T || G || 2 || 408 || F || C
 
|-
  
|-
−
|rs11549938 || ATC || CTC || A || C || 1 || 81 || M || L
 +
|rs137852870 || CAG || AAG || T || A || 1 || 437 || Y || N
 
|-
  
|-
−
|rs10853751 || TGC || TTC || C || T || 2 || 4 || T || M
 +
|rs11549938 || ATC || CTC || A || C || 1 || 81 || M || L
 
|-
  
|-
 
|}
  
|}
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!Mutated Residue
  
!Mutated Residue
 
|-
  
|-
−
|rs114716391 || TTC || TTT || G || T || 3 || 215 || A || A
 +
|rs17173144 || TGC || TGT || C || T || 3 || 4 || I || I
 
|-
  
|-
−
|rs80014754 || CTG || CTA || C || A || 3 || 38 || P || P
 +
|rs34541442 || TTA || ATA || C || A || 1 || 11 || R || R
 
|-
  
|-
 
|rs75733136 || ATC || ATA || C || A || 3 || 18 || S || S
  
|rs75733136 || ATC || ATA || C || A || 3 || 18 || S || S
−
|-
  
−
|rs62637712 || CTG || CTT || C || T || 3 || 37 || P || P
  
−
|-
  
−
|rs61737367 || AAC || AAT || C || T || 3 || 279 || R || R
  
−
|-
  
−
|rs55940366 || AAG || AAT || C || T || 3 || 324 || L || L
  
−
|-
  
−
|rs34541442 || TTA || ATA || C || A || 1 || 11 || R || R
  
−
|-
  
−
|rs34492894 || CCC || CCT || C || T || 3 || 418 || L || L
  
 
|-
  
|-
 
|rs34169026 || AGC || AGT || C || T || 3 || 31 || A || A
  
|rs34169026 || AGC || AGT || C || T || 3 || 31 || A || A
 
|-
  
|-
−
|rs17173144 || TGC || TGT || C || T || 3 || 4 || I || I
 +
|rs62637712 || CTG || CTT || C || T || 3 || 37 || P || P
  +
|-
  +
|rs80014754 || CTG || CTA || C || A || 3 || 38 || P || P
 
|-
  
|-
 
|rs11549937 || GAC || GAC || G || C || 3 || 96 || L || L
  
|rs11549937 || GAC || GAC || G || C || 3 || 96 || L || L
 
|-
  
|-
 
|rs10404506 || GAA || GAT || C || T || 3 || 212 || I || I
  
|rs10404506 || GAA || GAT || C || T || 3 || 212 || I || I
  +
|-
  +
|rs114716391 || TTC || TTT || G || T || 3 || 215 || A || A
  +
|-
  +
|rs61737367 || AAC || AAT || C || T || 3 || 279 || R || R
 
|-
  
|-
 
|rs284652 || ACA || ACT || C || T || 3 || 323 || F || F
  
|rs284652 || ACA || ACT || C || T || 3 || 323 || F || F
  +
|-
  +
|rs55940366 || AAG || AAT || C || T || 3 || 324 || L || L
 
|-
  
|-
 
|rs4674 || GCC || GCG || A || G || 3 || 406 || L || L
  
|rs4674 || GCC || GCG || A || G || 3 || 406 || L || L
  +
|-
  +
|rs34492894 || CCC || CCT || C || T || 3 || 418 || L || L
 
|-
  
|-
 
|}
  
|}

Revision as of 14:33, 18 June 2011

General

Maple syrup urine disease is an autosomal recessive disorder that affects the amino acid metabolism. The disease is caused by a defect in the branched-chain alpha-keto acid dehydrogenase complex which blocks oxidative decarboxylation. The result is a rising concentration of branched-chain amino acids. MSUD is caused by mutations in the gene coding for the alpha subunit of the branched-chain keto acid dehydrogenase(BCKDHA).


Reference Sequences: Reference_Sequence_BCKDHA

HGMD

Searching for "BCKDHA" a total of 39 mutations are reported, comprised of the following mutation types:

  • missense/nonsense: 33 mutations
  • small deletions: 3 mutations
  • small insertions: 1 mutation
  • gross deletions: 1 mutation
  • complex rearrangements: 1 mutation

For us the missense/nonsense mutations are the most interesting ones, as a single nucleotide change can lead to the phenotype of Maple Syrup Urine Disease.

Codon change Amino Acid change Codon number
gCAG-GAG Gln-Glu 80
ACG-ATG THr-Met 106
cCGG-TGG Arg-Trp 114
gTAT-AAAT Tyr-Asn 121
CGG-CAG Arg-Gln 122
cCAG-AAG Gln-Lys 145
ATC-ACC Ile-Thr 168
GCG-GTG Ala-Val 171
GCG-GTG Ala-Val 175
cGGC-AGC Gly-Ser 204
cGCT-ACT Ala-Thr 208
TGC-TAC Cys-Thr 213
cCGG-TGG Arg-Trp 220
AAT-AGT Asn-Ser 222
GGC-GAC Gly-Asp 238
tGCA-CCA Ala-Pro 240
aCGA-TGA Arg-Term 242
cGGG-AGG Gly-Arg 245
cCGC-TGC Arg-Cys 252
CGC-CAC Arg-His 252
tGGT-AGT Gly-Ser 255
GAT-GCT Asp-Ala 257
ACA-AGA Thr-Arg 265
cCGA-TGA Arg-Term 269
ATC-ACC Ile-Thr 281
cGAG-AAG Glu-Lys 282
gGCC-ACC Ala-Thr 283
CGC-CAC Arg-His 301
cCGG-TGG Arg-Trp 318
TTC-TGC Phe-Cys 364
cGTG-ATG Val-Met 367
TAT-TGT Tyr-Cys 368
cTAC-AAC Tyr-Asn 393


dbSNP

results for the SNPs search with BCKDHA:

-all: 742

-human: 371

SNPs in human

RefSeq ID SNP Reference Sequence Nucleotide Position Nt old Nt new Codon pos SilentSNP Changed AA
rs137852876 CTTGAGTGCCCCATCATCTTCTTCTG[C/G]CGGAACAATGGCTACGCCATCTCCA NM_000709.3 792 C G 263 0 S
rs137852875 TGATGTGTTTGCCGTATACAACGCCA[C/G]AAAGGAGGCCCGACGGCGGGCTGTG NM_000709.3 929 C G 309 0 S
rs137852874 CAGCCAGTGAGGGGGACGCCCATGCC[A/G]GCTTCAACTTCGCTGCCACACTTGA NM_000709.3 745 G A 248 0 R
rs137852873 TTGAGTGCCCCATCATCTTCTTCTGC[C/T]GGAACAATGGCTACGCCATCTCCAC NM_000709.3 793 C T 264 0 Y
rs137852872 GCCCAAACCCAACCCCAACCTACTCT[G/T]CTCAGACGTGTATCAGGAGATGCCC NM_000709.3 1226 T G 408 0 K
rs137852871 GTGTCCCCACAGCAGCACGAGGCCCC[A/G]GGTATGGCATCATGTCAATCCGCGT NM_000709.3 868 G A 289 0 R
rs137852870 GCCACCTGCAGACCTACGGGGAGCAC[A/T]ACCCACTGGATCACTTCGATAAGTG NM_000709.3 1312 T A 437 0 W
rs114716391 CTCACCACCCTCTCATCCCCTGCAGC[G/T]GTGGGGGCGGCGTACGCAGCCAAGC NM_000709.3 648 G T 215 1 K
rs111855817 TGCCCTCCTGCTGCTGCGGCAGCCTG[A/G]GGCTCGGGGACTGGCTAGATCTGTG NM_000709.3 86 G A 28 0 R
rs80014754 CTCTGCTCTCTTCCCCAGCACCCCCC[A/C]AGGCAGCAGCAGCAGTTTTCATCTC NM_000709.3 117 C A 38 0 M
rs62637712 TTTTCTCTCTCTCTTTCTTTCTGTAC[C/T]TCTCTTTCCTTTTTCTTTTTTTTTC NM_000709.3 114 C G 37 0 B
rs61737367 TCCACGCCCACCTCTGAGCAGTATCG[C/T]GGCGATGGCATTGGTATGGGCTCTG NM_000709.3 840 C T 279 0 Y
rs61736656 ATTACTGGGATAAACAGGACCACCCC[A/G]TCTCCCGGCTGCGGCACTATCTGCT NM_000709.3 1081 A G 360 0 R
rs55940366 GCTGTGGCAGAGAACCAGCCCTTCCT[C/T]ATCGAGGCCATGACCTACAGGTGCC NM_000709.3 975 C T 324 0 Y
rs34956071 TAGGTGTGCTGATGTATCGGGACTAC[C/T]CCCTGGAACTATTCATGGCCCAGTG NM_000709.3 508 C T 169 0 Y
rs34589432 CCTCTGCTCTCTTCCCCAGCACCCCC[A/C]CAGGCAGCAGCAGCAGTTTTCATCT NM_000709.3 116 C A 38 0 M
rs34541442 TAGCGATCGCTGCAGCGAGGGTCTGG[A/C]GGCTAAACCGTGGTTTGAGCCAGGC NM_000709.3 34 C A 11 0 M
rs34492894 GTGTATCAGGAGATGCCCGCCCAGCT[C/T]CGCAAGCAGCAGGAGTCTCTGGCCC NM_000709.3 1260 C T 419 0 Y
rs34442879 GGGGAGTGCCGCCGCCCTGGACAACA[C/T]GGACCTGGTGTTTGGCCAGTACCGG NM_000709.3 452 C T 150 0 Y
rs28940288 ACTTCGGCGAGGGGGCAGCCAGTGAG[A/G]GGGACGCCCATGCCGGCTTCAACTT NM_000709.3 730 G A 243 0 R
rs17173144 TTGTTAGCCAAGATGGCGGTAGCGAT[C/T]GCTGCAGCGAGGGTCTGGCGGCTAA NM_000709.3 15 C T 4 0 Y
rs11549938 TCTCTGGAATCCCCATCTACCGCGTC[A/C]TGGACCGGCAAGGCCAGATCATCAA NM_000709.3 244 A C 81 0 M
rs11549937 ATCAACCCCAGCGAGGACCCCCACCT[C/G]CCGAAGGAGAAGGTGCTGAAGCTCT NM_000709.3 291 G C 96 0 S
rs10404506 ATCTCCTCTCCACTGGCCACGCAGAT[C/T]CCTCAGGGTGAGGATGCATGCCCTG NM_000709.3 639 C T 212 0 Y
rs284652 CACCTGTAGGTCATGGCCTCGATGAG[A/G]AAGGGCTGGTTCTCTGCCACAGCCC NM_000709.3 972 C T 323 0 R
rs4674 ATCTCCTGATACACGTCTGAGAAGAG[C/T]AGGTTGGGGTTGGGTTTGGGCTTCC NM_000709.3 1221 A G 406 0 Y


The dbSNP mutation positions in the amino acid sequence are relative the RefSeq entry NP_001158255.1, which is exactly the protein sequence listed in Uniprot.

Missense Mutations annotated in dbSNP

RefSeq ID RefCodon Mutated Codon Reference Allele Mutated Allele Mutation Frame Codon Number Reference Residue Mutated Residue
rs10853751 TGC TTC C T 2 4 T M
rs111855817 CGT CAT G A 2 28 G E
rs34500671 CAG CAG C G 3 32 C W
rs34589432 CTG CAG C A 2 38 P H
rs34442879 GAG GTG C T 2 150 T M
rs34956071 GGC TGC C T 1 169 P S
rs28940288 AGG AGG G A 1 243 G R
rs137852874 TAC AAC G A 1 248 G S
rs137852876 TTC TTG C G 3 263 C W
rs137852873 AAC TAC C T 1 264 R W
rs137852871 ACC ACC G A 1 288 G R
rs137852875 TCA TGA C G 2 308 T R
rs61736656 CGC GGC A G 1 359 I V
rs137852872 GAG GGG T G 2 408 F C
rs137852870 CAG AAG T A 1 437 Y N
rs11549938 ATC CTC A C 1 81 M L

Silent mutations annotated in dbSNP

RefSeq ID RefCodon Mutated Codon Reference Allele Mutated Allele Mutation Frame Codon Number Reference Residue Mutated Residue
rs17173144 TGC TGT C T 3 4 I I
rs34541442 TTA ATA C A 1 11 R R
rs75733136 ATC ATA C A 3 18 S S
rs34169026 AGC AGT C T 3 31 A A
rs62637712 CTG CTT C T 3 37 P P
rs80014754 CTG CTA C A 3 38 P P
rs11549937 GAC GAC G C 3 96 L L
rs10404506 GAA GAT C T 3 212 I I
rs114716391 TTC TTT G T 3 215 A A
rs61737367 AAC AAT C T 3 279 R R
rs284652 ACA ACT C T 3 323 F F
rs55940366 AAG AAT C T 3 324 L L
rs4674 GCC GCG A G 3 406 L L
rs34492894 CCC CCT C T 3 418 L L

results for the gene search with BCKDHA

mRNA pos aa position function mutation aa change
54 5 synonymous C/T -
72 12 synonymous C/A -
125 29 missense G/A Gly/Glu
153 83 synonymous C/G, C/T -
155 39 missense C/A Pro/His
156 39 synonymous C/A -
238 82 missense A/C Met/Leu
330 97 synonymous G/C -
491 151 missense C/T Thr/Met
547 170 missense C/T Pro/Ser
678 213 synonymous C/T -
687 216 synonymous G/T -
769 244 missense G/A Gly/Arg
879 280 synonymous C/T -
1011 324 synonymous C/T -
1012 325 frame shift C/ -
1014 325 synonymous C/T -
1120 361 missense A/G Ile/Val
1260 407 synonymous A/G -
1299 420 synonymous C/T -


Point mutations can have an influence on the amino acids or not depending on the kind of the point mutation. There are two different types: synonymous and non-synonymous mutations.

If a point mutation is synonymous it means that the change occurs only in the nucleotide sequence but not in the amino acid sequence. This is possible because of the fact that amino acids are encoded by three nucleotides (codons) and some of the amino acids are encoded by more than one possible arrangement of nucleotides. So it can happen that when there is a mutation in the nucleotide sequence there is also a change in the codon but both codons encode the same amino acid.

The other possibility is that a mutation is non-synonymous which means that the mutation has an influence on the amino acid sequence and the amino acid changes. This change can have more or less severe because amino acids have several properties. When an amino acid is replaced by an amino acid which has the same properties the change is not so grave as the change to an amino acid with completely different properties.

MAVAIAAARVWRLNRGLSQAALLLLRQPGARGLARSHPPRQQQQFSSLDDKPQFPGASAEF
IDKLEFIQPNVISGIPIYRVMDRQGQIINPSEDPHLPKEKVLKLYKSMTLLNTMDRILYE
SQRQGRISFYMTNYGEEGTHVGSAAALDNTDLVFGQYREAGVLMYRDYPLELFMAQCYGN
ISDLGKGRQMPVHYGCKERHFVTISSPLATQIPQAVGAAYAAKRANANRVVICYFGEGAA
SEGDAHAGFNFAATLECPIIFFCRNNGYAISTPTSEQYRGDGIAARGPGYGIMSIRVDGN
DVFAVYNATKEARRRAVAENQPFLIEAMTYRIGHHSTSDDSSAYRSVDEVNYWDKQDHPI
SRLRHYLLSQGWWDEEQEKAWRKQSRRKVMEAFEQAERKPKPNPNLLFSDVYQEMPAQLR
KQQESLARHLQTYGEHYPLDHFDK

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