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).

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 SNPs in 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