Mapping SNPs BCKDHA
Contents
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).
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
| ID | mutation in sequence | amino acid | position |
|---|---|---|---|
| rs137852876 | CTTGAGTGCCCCATCATCTTCTTCTG[C/G]CGGAACAATGGCTACGCCATCTCCA | Ser | pos=251 |
| rs137852875 | TGATGTGTTTGCCGTATACAACGCCA[C/G]AAAGGAGGCCCGACGGCGGGCTGTG | Ser | pos=251 |
| rs137852874 | CAGCCAGTGAGGGGGACGCCCATGCC[A/G]GCTTCAACTTCGCTGCCACACTTGA | Arg | pos=251 |
| rs137852873 | TTGAGTGCCCCATCATCTTCTTCTGC[C/T]GGAACAATGGCTACGCCATCTCCAC | Tyr | pos=251 |
| rs137852872 | GCCCAAACCCAACCCCAACCTACTCT[G/T]CTCAGACGTGTATCAGGAGATGCCC | Lys | pos=251 |
| rs137852871 | GTGTCCCCACAGCAGCACGAGGCCCC[A/G]GGTATGGCATCATGTCAATCCGCGT | Arg | pos=251 |
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 kind of point mutation. There are two different types: synonymous ans non-synonymous mutations. If a point mutation is sysnonymous 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 (codon) and some of the amino acids are encoded by more than one possible arrangement of nucleotides.
