View source for Mapping SNPs BCKDHA

== 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.

{|border="1"
!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 ===

{|border="1" style="text-align:center; border-spacing:0;"
!RefSeq ID
!SNP
!Reference Sequence
!Nucleotide Position
!Nt old
!Nt new
!Codon pos
|-
| rs137852876 || CTTGAGTGCCCCATCATCTTCTTCTG[C/G]CGGAACAATGGCTACGCCATCTCCA || NM_000709.3 || 792 || C || G || 264 || S
|-
| rs137852875 || TGATGTGTTTGCCGTATACAACGCCA[C/G]AAAGGAGGCCCGACGGCGGGCTGTG || NM_000709.3 || 929 || C || G || 310 || S
|-
| rs137852874 || CAGCCAGTGAGGGGGACGCCCATGCC[A/G]GCTTCAACTTCGCTGCCACACTTGA || NM_000709.3 || 745 || G || A || 248 || R
|-
| rs137852873 || TTGAGTGCCCCATCATCTTCTTCTGC[C/T]GGAACAATGGCTACGCCATCTCCAC || NM_000709.3 || 793 || C || T || 264 || Y
|-
| rs137852872 || GCCCAAACCCAACCCCAACCTACTCT[G/T]CTCAGACGTGTATCAGGAGATGCCC || NM_000709.3 || 1226 || T || G || 409 || K
|-
| rs137852871 || GTGTCCCCACAGCAGCACGAGGCCCC[A/G]GGTATGGCATCATGTCAATCCGCGT || NM_000709.3 || 868 || G || A || 289 || R
|-
| rs137852870 || GCCACCTGCAGACCTACGGGGAGCAC[A/T]ACCCACTGGATCACTTCGATAAGTG || NM_000709.3 || 1312 || T || A || 437 || W
|-
| rs114716391 || CTCACCACCCTCTCATCCCCTGCAGC[G/T]GTGGGGGCGGCGTACGCAGCCAAGC || NM_000709.3 || 648 || G || T || 216 || K
|-
| rs111855817 || TGCCCTCCTGCTGCTGCGGCAGCCTG[A/G]GGCTCGGGGACTGGCTAGATCTGTG || NM_000709.3 || 86 || G || A || 29 || R
|-
| rs80014754 || CTCTGCTCTCTTCCCCAGCACCCCCC[A/C]AGGCAGCAGCAGCAGTTTTCATCTC || NM_000709.3 || 117 || C || A || 39 || M
|-
| rs62637712 || TTTTCTCTCTCTCTTTCTTTCTGTAC[C/T]TCTCTTTCCTTTTTCTTTTTTTTTC || NM_000709.3 || 114 || C || G || 38 || B
|-
| rs61737367 || TCCACGCCCACCTCTGAGCAGTATCG[C/T]GGCGATGGCATTGGTATGGGCTCTG || NM_000709.3 || 840 || C || T || 280 || Y
|-
| rs61736656 || ATTACTGGGATAAACAGGACCACCCC[A/G]TCTCCCGGCTGCGGCACTATCTGCT || NM_000709.3 || 1081 || A || G || 360 || R
|-
| rs55940366 || GCTGTGGCAGAGAACCAGCCCTTCCT[C/T]ATCGAGGCCATGACCTACAGGTGCC || NM_000709.3 || 975 || C || T || 325 || Y
|-
| rs34956071 || TAGGTGTGCTGATGTATCGGGACTAC[C/T]CCCTGGAACTATTCATGGCCCAGTG || NM_000709.3 || 508 || C || T || 169 || Y
|-
| rs34589432 || CCTCTGCTCTCTTCCCCAGCACCCCC[A/C]CAGGCAGCAGCAGCAGTTTTCATCT || NM_000709.3 || 116 || C || A || 39 || M
|-
| rs34541442 || TAGCGATCGCTGCAGCGAGGGTCTGG[A/C]GGCTAAACCGTGGTTTGAGCCAGGC || NM_000709.3 || 34 || C || A || 11 || M
|-
| rs34492894 || GTGTATCAGGAGATGCCCGCCCAGCT[C/T]CGCAAGCAGCAGGAGTCTCTGGCCC || NM_000709.3 || 1260 || C || T || 420 || Y
|-
| rs34442879 || GGGGAGTGCCGCCGCCCTGGACAACA[C/T]GGACCTGGTGTTTGGCCAGTACCGG || NM_000709.3 || 452 || C || T || 151 || Y
|-
| rs28940288 || ACTTCGGCGAGGGGGCAGCCAGTGAG[A/G]GGGACGCCCATGCCGGCTTCAACTT || NM_000709.3 || 730 || G || A || 243 || R
|-
| rs17173144 || TTGTTAGCCAAGATGGCGGTAGCGAT[C/T]GCTGCAGCGAGGGTCTGGCGGCTAA || NM_000709.3 || 15 || C || T || 5 || Y
|-
| rs11549938 || TCTCTGGAATCCCCATCTACCGCGTC[A/C]TGGACCGGCAAGGCCAGATCATCAA || NM_000709.3 || 244 || A || C || 81 || M
|-
| rs11549937 || ATCAACCCCAGCGAGGACCCCCACCT[C/G]CCGAAGGAGAAGGTGCTGAAGCTCT || NM_000709.3 || 291 || G || C || 97 || S
|-
| rs10404506 || ATCTCCTCTCCACTGGCCACGCAGAT[C/T]CCTCAGGGTGAGGATGCATGCCCTG || NM_000709.3 || 639 || C || T || 213 || Y
|-
| rs284652 || CACCTGTAGGTCATGGCCTCGATGAG[A/G]AAGGGCTGGTTCTCTGCCACAGCCC || NM_000709.3 || 972 || C || T || 324 || R
|-
| rs4674 || ATCTCCTGATACACGTCTGAGAAGAG[C/T]AGGTTGGGGTTGGGTTTGGGCTTCC || NM_000709.3 || 1221 || A || G || 407 || Y
|-
|}

'''results for the gene search with BCKDHA'''

{|border="1"
!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 kind of 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.