Difference between revisions of "BCKDHA"
From Bioinformatikpedia
m (→Reference sequence) |
m (→Disease causing mutations) |
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| + | BCKDHA is the α subunit of [[Maple_Syrup_Urine_Disease#Branched-chain_.CE.B1-keto_acids_dehydrogenase_complex|branched-chain α-keto acid dehydrogenase complex]]. The gene which encodes BCKDHA locates on chromosome 19. |
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| − | ==Summary== |
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| − | The gene BCKDHA encodes the E1 subunit of the human branched-chain alpha-keto acid dehydrogenase complex (BCKDC). |
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| − | It locates on chromosome 19 and has 34,217 bp. |
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==Reference sequence== |
==Reference sequence== |
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| + | |||
| + | * [[#Genomic_sequence|Genomic sequence]] |
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| + | * [[#mRNA_transcript|mRNA transcript]] |
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| + | * [[#Protein|Protein sequence]] |
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| + | |||
| + | ===Genomic sequence=== |
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<nowiki>>gi|260593636|ref|NG_013004.1| Homo sapiens branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA), RefSeqGene on chromosome 19 |
<nowiki>>gi|260593636|ref|NG_013004.1| Homo sapiens branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA), RefSeqGene on chromosome 19 |
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GGCAGCTGGTAGGGAGGAGCTGGGGGGGTGATTTTGACAAACTGGGCACCACTCAGAGGTTCAGCAGGGC |
GGCAGCTGGTAGGGAGGAGCTGGGGGGGTGATTTTGACAAACTGGGCACCACTCAGAGGTTCAGCAGGGC |
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| Line 494: | Line 498: | ||
AGCCAGGCCCCAGGCAGACAGCTTCACAATCTCCCATAGTCCCCGCCAACCCCCATAACAGATTCTCTCG |
AGCCAGGCCCCAGGCAGACAGCTTCACAATCTCCCATAGTCCCCGCCAACCCCCATAACAGATTCTCTCG |
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GTCCCAGATCCTAAACAGCTCCCCTGACCCAGGGACCTCGTTGGTCCTTATTCCTAG</nowiki> |
GTCCCAGATCCTAAACAGCTCCCCTGACCCAGGGACCTCGTTGGTCCTTATTCCTAG</nowiki> |
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| + | |||
| + | ===mRNA transcript=== |
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| + | <nowiki>>gi|258645170|ref|NM_000709.3| Homo sapiens branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA), nuclear gene encoding mitochondrial protein, transcript variant 1, mRNA |
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| + | CTACGTGAGTGCCGGACCGCTGAGTGGTTGTTAGCCAAGATGGCGGTAGCGATCGCTGCAGCGAGGGTCT |
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| + | GGCGGCTAAACCGTGGTTTGAGCCAGGCTGCCCTCCTGCTGCTGCGGCAGCCTGGGGCTCGGGGACTGGC |
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| + | TAGATCTCACCCCCCCAGGCAGCAGCAGCAGTTTTCATCTCTGGATGACAAGCCCCAGTTCCCAGGGGCC |
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| + | TCGGCGGAGTTTATAGATAAGTTGGAATTCATCCAGCCCAACGTCATCTCTGGAATCCCCATCTACCGCG |
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| + | TCATGGACCGGCAAGGCCAGATCATCAACCCCAGCGAGGACCCCCACCTGCCGAAGGAGAAGGTGCTGAA |
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| + | GCTCTACAAGAGCATGACACTGCTTAACACCATGGACCGCATCCTCTATGAGTCTCAGCGGCAGGGCCGG |
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| + | ATCTCCTTCTACATGACCAACTATGGTGAGGAGGGCACGCACGTGGGGAGTGCCGCCGCCCTGGACAACA |
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| + | CGGACCTGGTGTTTGGCCAGTACCGGGAGGCAGGTGTGCTGATGTATCGGGACTACCCCCTGGAACTATT |
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| + | CATGGCCCAGTGCTATGGCAACATCAGTGACTTGGGCAAGGGGCGCCAGATGCCTGTCCACTACGGCTGC |
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| + | AAGGAACGCCACTTCGTCACTATCTCCTCTCCACTGGCCACGCAGATCCCTCAGGCGGTGGGGGCGGCGT |
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| + | ACGCAGCCAAGCGGGCCAATGCCAACAGGGTCGTCATCTGTTACTTCGGCGAGGGGGCAGCCAGTGAGGG |
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| + | GGACGCCCATGCCGGCTTCAACTTCGCTGCCACACTTGAGTGCCCCATCATCTTCTTCTGCCGGAACAAT |
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| + | GGCTACGCCATCTCCACGCCCACCTCTGAGCAGTATCGCGGCGATGGCATTGCAGCACGAGGCCCCGGGT |
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| + | ATGGCATCATGTCAATCCGCGTGGATGGTAATGATGTGTTTGCCGTATACAACGCCACAAAGGAGGCCCG |
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| + | ACGGCGGGCTGTGGCAGAGAACCAGCCCTTCCTCATCGAGGCCATGACCTACAGGATCGGGCACCACAGC |
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| + | ACCAGTGACGACAGTTCAGCGTACCGCTCGGTGGATGAGGTCAATTACTGGGATAAACAGGACCACCCCA |
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| + | TCTCCCGGCTGCGGCACTATCTGCTGAGCCAAGGCTGGTGGGATGAGGAGCAGGAGAAGGCCTGGAGGAA |
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| + | GCAGTCCCGCAGGAAGGTGATGGAGGCCTTTGAGCAGGCCGAGCGGAAGCCCAAACCCAACCCCAACCTA |
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| + | CTCTTCTCAGACGTGTATCAGGAGATGCCCGCCCAGCTCCGCAAGCAGCAGGAGTCTCTGGCCCGCCACC |
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| + | TGCAGACCTACGGGGAGCACTACCCACTGGATCACTTCGATAAGTGAGACCTGCTCAGCCCACCCCCACC |
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| + | CATCCTCAGCTACCCCGAGAGGTAGCCCCACTCTAAGGGGAGCAGGGGGACCTGACAGCACACCACTGTC |
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| + | TTCCCCAGTCAGCTCCCTCTAAAATACTCAGCGGCCAGGGCGGCTGCCACTCTTCACCCCTGCTCCTCCC |
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| + | GGCTGTTACATTGTCAGGGGACAGCATCTGCAGCAGTTGCTGAGGCTCCGTCAGCCCCCTCTTCACCTGT |
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| + | TGTTACAGTGCCTTCTCCCAGGGGCTGGGTGAGGGCACATTCAGGACTAGAAGCCCCTCTGGGCATGGGG |
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| + | TGGACATGGCAGGTCAGCCTGTGGAACTTGCGCAGGTGCGAGTGGCCAGCAGAGGTCACGAATAAACTGC |
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| + | ATCTCTGCGCCTGGCTCTCTACCAAAAAAAAAAAAAAAAAA</nowiki> |
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| + | |||
| + | ===Protein=== |
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| + | <nowiki>>gi|11386135|ref|NP_000700.1| 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial isoform 1 precursor [Homo sapiens] |
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| + | MAVAIAAARVWRLNRGLSQAALLLLRQPGARGLARSHPPRQQQQFSSLDDKPQFPGASAEFIDKLEFIQP |
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| + | NVISGIPIYRVMDRQGQIINPSEDPHLPKEKVLKLYKSMTLLNTMDRILYESQRQGRISFYMTNYGEEGT |
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| + | HVGSAAALDNTDLVFGQYREAGVLMYRDYPLELFMAQCYGNISDLGKGRQMPVHYGCKERHFVTISSPLA |
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| + | TQIPQAVGAAYAAKRANANRVVICYFGEGAASEGDAHAGFNFAATLECPIIFFCRNNGYAISTPTSEQYR |
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| + | GDGIAARGPGYGIMSIRVDGNDVFAVYNATKEARRRAVAENQPFLIEAMTYRIGHHSTSDDSSAYRSVDE |
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| + | VNYWDKQDHPISRLRHYLLSQGWWDEEQEKAWRKQSRRKVMEAFEQAERKPKPNPNLLFSDVYQEMPAQL |
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| + | RKQQESLARHLQTYGEHYPLDHFDK</nowiki> |
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| + | |||
| + | ==Neutral mutations== |
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| + | |||
| + | ==Disease causing mutations== |
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| + | Several disease causing mutations are reported in [http://www.omim.org/entry/608348 OMIM]. Following table summarize the reported allelic variations: |
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| + | |||
| + | {| class="wikitable" border="1" style="width:500px" |
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| + | |+ Reported allelic variants in OMIM |
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| + | |- |
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| + | ! ID |
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| + | ! Variant type |
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| + | ! Mutation detail |
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| + | ! Cause |
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| + | ! Severity |
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| + | |- |
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| + | | 1 || substitution || TYR393ASN || [[Maple Syrup Urine Disease|MSUD]] type 1A || classic |
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| + | |- |
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| + | | 2 || deletion || 8-BP DEL, 887-894 || MSUD type 1A || classic |
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| + | |- |
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| + | | 3 || substitution || GLY245ARG || MSUD type 1A || intermediate |
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| + | |- |
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| + | | 4 || substitution || PHE364CYS || MSUD type 1A || intermediate |
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| + | |- |
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| + | | 5 || substitution || ARG220TRP || MSUD type 1A || classic |
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| + | |- |
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| + | | 6 || substitution || GLY204SER || MSUD type 1A || classic |
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| + | |- |
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| + | | 7 || substitution || THR265ARG || MSUD type 1A || classic |
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| + | |- |
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| + | | 8 || substitution || CYS219TRP || MSUD type 1A || classic |
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| + | |- |
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| + | | 9 || deletion || 1-BP DEL, 117C || MSUD type 1A || classic |
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| + | |} |
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| + | |||
| + | ==References== |
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| + | [http://www.ncbi.nlm.nih.gov/gene/593 branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA)] |
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| + | |||
| + | [http://www.ncbi.nlm.nih.gov/nuccore/260593636?report=graph RefSeqGene of branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA)] |
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| + | |||
| + | [http://www.ncbi.nlm.nih.gov/nuccore/NM_000709.3 Homo sapiens branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA), nuclear gene encoding mitochondrial protein, transcript variant 1, mRNA] |
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| + | |||
| + | [http://www.ncbi.nlm.nih.gov/nuccore/NM_001164783.1 Homo sapiens branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA), nuclear gene encoding mitochondrial protein, transcript variant 2, mRNA] |
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| + | |||
| + | [http://www.ncbi.nlm.nih.gov/protein/NP_000700.1 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial isoform 1 precursor (Homo sapiens)] |
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| + | |||
| + | [http://www.omim.org/ Online Mendelian Inheritance in Man] |
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Latest revision as of 17:04, 28 April 2013
BCKDHA is the α subunit of branched-chain α-keto acid dehydrogenase complex. The gene which encodes BCKDHA locates on chromosome 19.
Contents
Reference sequence
Genomic sequence
>gi|260593636|ref|NG_013004.1| Homo sapiens branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA), RefSeqGene on chromosome 19 GGCAGCTGGTAGGGAGGAGCTGGGGGGGTGATTTTGACAAACTGGGCACCACTCAGAGGTTCAGCAGGGC CCAATTACCAGGCAGCCCAATCTTCGGCCTCAGGATCACTTCGAGTGTGGCCTTGTTGAAAATCTCTTTG CTGACCTTCACCTCGGCCGGCCCGTACACACCCGCCAGGACAGAGGTGTCACCTGAGGAGACAGCAGGGA GGGCCTCACTCACAGCTTCCCTGCTCCTGGGGCCCCATTTGTGGCACTGAGCCTGACGGCCAGGGCTCCC CACGTCACCCCCGCCATTTGTTGGTACTGATTCTTTGAGCACTCACTTCATTTCTCTCATTTGTAAAATG GGGAAAATAGCAGTCCCTCCCCGCTAGCGTCTTGTGAGGATCAAAGGACACAATTCACAGAAAACACTTA GAACACTGCGGGGCTCACGCTGAATGTGCAACAGACTTTAGCTGTATTAGTAACATTCGTCCATTCAGGC ATTCAGGCAGGGTCTCACTCTCATTGCCCAGGCTGGAGTGCAGTGGTGCCATCACGGCTCATTGCAGCCT TGACCTTCTGGGCTCAAGTGATCCTCCCGCCTCAGCCTCCCAAGTAGCTGGAACTACAGGCATGTGCCAC CATGCCTGACTAATTTTTATATTTTTAGTAGAGAGGGGATTTTGCCATGTTGCTCAGGCGGGTTTCGAAC TCCTGGGCAACTGTAATCCCAAGGTGCTAGGATTACAGGCGTGAGCTACCACGCCTGGCCCTGATATTAG TAATTTTTTTTTTTTTAATGAGATGGAGTCTTGCTCTGTCGCCCAGGCTGGAGTGCAGTGGCGTAATCTC GGCTCACCGCAACCTCTGCCTCCCGGGTTCAAGCAGTTCTCCTGCCTCAGCCTACTGAGTAGCTGGGATT ACAGGCGCGCGCCACCACACCTGGCTAATTTTTTTATTTTTAGTAGAGACTGGGTTTCACCATGTTGGTC AGGCTGGTCTCGAACTTCCTGACCTCATGATCTGCCCGCCTCCCAAAGCGCTGGGATTACAGGCGTGAGC CACTGTGCCCGGCTGGTATTAGTAACTTTTAACAGGAAGTTCTTCCTGAAAGCTAACCATCCTCCCTCTT ACTGCAGCTGCTCTCAACTTCTCTTTCCAAAGCTTCCCCAGCCCAGCTCTTCCCTTAGGCACTGGCCCCC AAATTTTGCATCAGTCTGGACACCTGAGAAAGGGATAATATCTGGAATGAATCCTGATTCCTTATTTCCC CAGAAGCTATGAACGGGGTACAGGAGGTAAAACCTAAGAAATAAACAGCCTGGCTTCTAGTACTGTCTGC TGTAATCCCAGCACTTTGGGAGGCTGAGGTGGGTGGATCACCTGAGGTCAGGAGTTTGAGACCATCCTAG TCAACATGGTGAAACCCTATCTCTACTAAAGATACAAAAATTAGCTGGGCATAGTGGTGGGTGCCTGTAA TCTCAGCTACTTGGGAGGCCGACGCAGGAGAATTGCTGGAACCGGGGAGGCGGAGGTTGCAGTGAGCCGA GATCACACCATTGCACTCCAGCCTGGACAATAACAGCAAGGCTTAGTCTCAATAAAAAAAAAAAAATACA TTTTAGGCCAGGCATGGTGGCTCACACCTGTAATCCCAGCACTATGGAGGCCCAGGTGGGAGGACTGCTT GAGGCCAGGAGTTTGAGACCAGCCTGAGCAGCATAGGAAGACTCCTGTCTCTATTTTCTTTTTTGGGACA GAGTTTCCCTCTGTCACCCAGGAGGCTGGAGTGCAGTGGCGCAATCTCAGTTCACTGCAACCTCCGCCTC CCAGGCTCAAGTGATTCTTGTACCTCAACCTCCAGAGTAGCTGAGATTACAGGTGCGTGCTACCACATCC GACTAATTTTTGTATTTTTAGTAGAGATGGGTTTTCACCATGTTGGCCAATCTGGTCTCAGAACTCCTGA CCTCAACCAAGCGAGGTGGCTCACGCCTGTAATCCCAGCACTGTGGGAGGCTGAGGCAGGTGGATCACAG GGTCAGGAGTTCAAGATCAGCCTGGCCAACATGGTGAAACCCCGTCTCTACTAAAAACCACAAAAATTAG CCGGGCGCGGTGGCACGCACCTGTGGTCCCAGCTACTCAGGAGGCTGAGGCAGAAGAATTGCTTGAACCC GGGAGGTGGAGGGTGCAGTGAGCCACGATCACTTCACTGCACTCCAGCCTGGGCGACAGGGCGAGACTCC ATCTCAAAAAAAAAAAAAGAAAAAAAAAAAAAGAACTCCTGACCTCAGAGGCCTCCCAAAGTGCTGGGAT TACCGCTGTGAGCAACTGCACCCGGCCTCTTCTTAATTCTTACGTTCGAAGAAACTTTAGGTATCTCAAT TCAGCATAAGCGCTAAGCCTGAGGGAGGGCCTGGGAAGGTCCTTGGTTAAGGCCGTATTTCCTGGGAAGC CCAATTTGCCCTTACACGGAAGGTATGCTTAGTTCCAGGAGAAACTGCCCTGAGGACTGGAGAAGTTACC AAAACAGAACTTGCCTCTGGCTCCAGATGAACTGCCTGTGTTTTGCCCGAGCACAAGAGTCTCTCCCCTC TCACCTTCTTGAAGACGTGGCTCCAGCAATTCTCTCCCCTGTTGACCCCACAACAATCTACAACTCCTGC CCCACTTATCTGATCCTCTTACAGCAGAACTCCTGAACAGCTGCCTCTTCTTCCTTTTCTGTGACCCCAC CACTCCATTGCGGCAGCTCAACATCGTCACCACTGACCTCCAAATGATCAACCCTCCCATGACCCGGCTG TCAGTAAGGCTGAAACAGCTGGTCAGCCCTCACATCTCAGACATGCTCTTTTCTTGGCCCCAGGTCACCA CCATCTCCTGGTTTCCCCCTAACTCTCTGGGCGTTCCTTCTGAGTCTCCTTTGCTAGCTTGTCACATGTC TCTGACTGCTCAAGTTGGAAGGCCTAGGGCTTGGTCCTGGGACCTCTTCTCTTTTCCATCTACACTCACT TCGTTCAGGCAATAGCCTGAAATACCATCTATATAGCCAGAGAGTTCCAAATTGCCTATGTCCAGCTTGG GTCTCTCTTCTGATTTCCAGACTTGTACAGATCTGGGCAGAAACCTTAGTTATGCCTGAATCTTTTTCCT CGCACTCAAACCAAACTATACGTAAGTTTTGTCCGTATTACTTTCAAACTACATCCAGAATCTCATCACC TCCACTACTCCTGCTCTGGCTGGAGCCACCATCACCTCCCTGTTTTCCCCCATACTCCCCACAATCAACA CAGCAGCCAAATTTTGTTAAAATGTATTGGGGCTGGGCGTGGTGGCTCATACCTGTATGAGCACTTTGGG AGGAGGATTGCTTGAGCCCAGGAGTTCAAGACCAACCTGGGTGACATCGTGAGACGCTGTCTCAATTTTT TTTTTTTTTGAGACAGAGTCTTGCTTTGTCGCTCACGCTGGAGTACAATGGCACGATCTCGGCCCACTGC AACTTCTGCCTCCCAGGTTCAAGTGATTGTCCTGCCTCAGCCTCCCGAGTAGCTGGGATTACAGGCGCCC GCCACCATGCCTGGCTAGTTTTTGTATTTTTAGTAGAGACAGGGTTTCGCCATGTTGGCCAGGCTGGTCT CGAACTCCTGACCTCAGGTGAGCCACAGGTCTTGGCCTCCCAAAGTGTGGGGATTACAGGCGTGAGCCAC CGCCCCCGGCCTCCCGTCTCAAACGTTAAAGAGAAATATTCTTGGAGTTAATCTACTTCTGAGAGTTATT TAGCTAGGAAAAGGGGATATTTGCTCTATAGGTAAGACTTGCCCTAATCTTTTTTTTTTTTTTTTTTTTG ACTTGCCCTAATCTTAGGGATATTTACTTGTGTGGAGAGATGCAGTGAGGTAGCGGTGGGGATGTATTTC TCAACCCAGCGCAATGACATTATCTTCAATTTGAGGAGTATTTACGTGGGTGAAAGATCCGCCACAGTCC ACAGTATGCAAATAGACAGGTTTGCTTCAGTCCGGGATGCAAGGACCTAGAGGGTGTGTGTGTGGGGGGT GGGGGTGGGAGGGTGGAGGAGGAATCGAGTTAAGGGGGATATTTACCCTGGCGAGGTGATTTTCCCTATT CTGAAATATCAATTCTTGGGCGGACAGTCTGCCCCTCCTCTCATTCTCAGAGATAGTTACAAAGATGGAA CTATCTTCTCCTTTCTAGTCGTGAGGGAGAGATGTGTGTATCCCTGCGTATTTAGTAGTATTCAATCGGA CAAGAAATCATGCATCAACGCAGGAGTGACATTTACCAGCTGGTATCGTGAGGAGGTGGGCACTCGGTTG CACAGTACACGGTAGTCCCTCTCCAAAAGAAAGACCTGGGTGAAGTTCTTACCTTGCAGGAAGGAAGCAG AGCCATCTGGCCGCGACAGCAGGTTCTGTTCGCAGGCAAAGTGCCGGAGGCTGCAGCCAGGACCCCGAGG GCTGGACCCTGTTCCATTTTCAGCACGGATTTTGGCGTCAGTATGCGTCTCCTCCTCCATCGCGCCGAGC CCACGTGCGGCTGCAGTTGTCACTTCCGCCTGGCAGCGCGCGCCGCAAACAGGCTGCGTAACCAGTGCGC ACGCGCCGGGCTGGGCCATCCTCCTGGGCGTCCGCACGTGGCTTAGCGTTTACCAACAATCTGGCTCCGC CCAGTCCCACCTCCTAACTCTGGCAACGCCATTGGACATTTGGGAACAGAAGGCAGGCCTTGGCATTGAT CCGCTTTACTCTGGGCCCCCGGGCCCTAAATCCCTGAGGCCCTGGTCAGGTTGCCCTCTTCTTTGCCTGT TACAGGAGTAACTACAATGAGGCGATTGGAGAAAATTTTGGGTAGATAGATTTTTTTTTCTCCAAATCTC TGTGCATTCTATCTACCACAGAACGGGAAGAAGATGGTTTTCTTGTCAGATGGTGCTGGAGTTTGCGTCA GGCACATAAAGAGGCAGCCCCGAATCTAGCCTACGTGAGTGCCGGACCGCTGAGTGGTTGTTAGCCAAGA TGGCGGTAGCGATCGCTGCAGCGAGGGTCTGGCGGCTAAACCGTGGTTTGAGCCAGGCTGCCCTCCTGCT GCTGCGGCAGCCTGGGGCTCGGGGACTGGCTAGATCTGTGAGTACCTGGGCCCCAGGCGGTTTTCCCAAA GGGGATTAGGGATGTAAAGGCTATCTTCAGAGTGTGGGGTCCCTGAAGGATATGAAGGAAGGGCTGTCAC AAAAGGGAAAAAGAGTGGGAGACTCCTTGGAGAAGACACCGAAGGGAAGATCTGCCACTTCCTTAGGAGA CGAAAAGAACTTCCACTTCTTTAGGAGAGGAAAAAACCCGTTTGCAACTTCTTTGTGGGCCCTGAGGGAG ACGACTTGAAGAGAGAGATGGGGGTTCCTTATTAGCTGCCACTGGTATTCAGGGGAGGCTCCTTGGAGGA ACAGGGGAAGACCGCAAGACCTTCTCCCTCAGGGTTTGGAGAATGAAACTGACTTTGTAAGGGAGGGACT TTCTTCTGGGCAAAGATCCCTCTTCAAGAAGAAGAAAGAAGAGAACAGGTCCCTGTCACAGGCTGCATAG GGCCTTGTATTTCTTTGCTCCTTTGCCACAATTCTGATTTTAAAATGAATTGTGTAAAAAATTTGTTTGA TTCCTGTGTCTCTTGATCGAATATCAAGACAGAGAATTCGTGTGTTCTGGACACTGTACAGAGGAGACGA TTAATATTTGTTGAATTAATGAGGGGAAAAAAGGAGGGAGAGAGGTACAGACAGGGCACTTTGCCCACAT TTCTTAGAAACACTTGAGAAGGCTTTGTTTCTTGTCAAAAGGGTCACAATCCCTTCAGGTGGATGCTGCT AAGGGCAAGATTACACTGCAAAAAACCTAGGTGGAAGCCTATCTTTAGACGGGGAGAGGCAATGGGTTGC AGAAGAGCTTTGAACTACAGTTGACAGATAGGAGAGTAGTGGTTACATGGGTGGATGCATGTCCTTGCTC TGCCGCTTTCCACTTGTGTAGCCTTGGCCAACGGACTGCACTTCTCTGGATCTATGGAGCTAATTTTCCT CTCTAAAATATTAACAGTGGCCACCTCATAGGGCTGTGAAAAATCAATATGTAAAATGCTAAGGACTGGA CCTGGCACATCCTAAGGGCAATAGGAATGTTGATAGTGAGGGTGGAGGGAAGGGACAGAAACTAACCTTG GAGATGGGGAGAAGAAAGGGGTGACCTTGGGAAGGCCTGGATTGGTGAGGCCCTGGGGAAAAAAATCTGA AAAGATATTGTGAGGTTGAGTCTGATCCTCTGATCCCCAATCCATAAGGAGGGGAAGATGGAATCTGTAG AAAGAAGCTCTGGGTAGGGGAACAAACGGGAGGAGGGTGAAGAAGATGGGCCAGGAGTAGGACGTAGTAG GTATCTAGGAACGGAGTCACTTGAAACAGGTAAATACAGAAGGGCTGCAGGAGCAAGGTGTGGGTAGGGC AGTCTCTTGCCTTTGGGCTGGAGACCTTTTCACTTTTTTTTTTTTTTTTTTTTTTGAGCAGTTCATATCC TCCACAGCTGATCTCAGTCCCAGGGGCCCATTGGCTGGGCAAGTGGGGCAGGAGGTGGGCAGGACTGGGG CAGGCTAGGGAAAGGTCATTTATGGCTGATTAAATCTTTCTCTCCTGTCTCAATCTCTTGATTACCTTTC CTCTTGCTTCCCCTACTTCATTTTTGGTGGGGAGTGGGGAGGGAAGAAGTCCCTACTTTTTATTTATATA TATTTAAATTTGTATTATCTTAAGAGTTATTGTTTTTTCCCCTTTATTTCTCCCACCTGTTCTTTCTCTC TTCTTCTTTCTTTCCTCTCCTTCTCCTCTCCTCTCCTCCCCTCTCCTTTTTCTTTTCTTTTCTTTTTCCC TTTCCTTTCCTTTCCTTTTCTCTTCTCTTTTCTCTCTCTCTTTCTTTCTGTACCTCTCTTTCCTTTTTCT TTTTTTTTCTTTTTTGAGACAGAGTTTCACTCTCTCGCCTAGGCTGGAGTGCAGCAGCATGATCTTGACT TACTGCAATCTCTGCCTGCCGAGTTCAAGCAATTCTCCTGCCTCAGCCTCCCTAGTAGCTGGGATTACAG GCATGCACTATCACGCCTGGCTAATTTTTGTATTTTTGGTAGGGACGAGGTTTCACCATGTTGTCCAGGC TGGTCTCGAACTTCTGGCCTCAAGTTCCGCCTGTCTTGGCCTCCAAAAGCATGAGCCACTGCGCCTAGCC TTTTCTTTTTTTGAGACAAGGTCTCACTCTGTCACCCAGGCTGGAGTGAGTGCAGTGGTGTGATCATGGC TCACTGCAGCCTCAACCTCCTGGGCTCAAGCAATCCCCCCACCTCCACCTCCTAAGTAGCTGGGACCACA GGCACGTGCTACTACGCCTGGCTAATTTTTAATTTTTTTTTTTTTTTTTGAGACGGAGTCTTGCTCTGTC ACCCAAGCTGGAGTGCAGTGGCACGATCTCGGCTCACTGCAACCTCCACTTCCCAGGTTCAAGTGATTCT CCTGCCTCAGCCTCCCAAATAGCTGGGACTACTGGCGTGCGCCACCATACCCAGTTAATTTTTGTATTTT TAGTAGAGATGGGGTTTCACCATGTTGACCAGGCTGGTCTTGAACTCCTGATCTAAGGTGATCTGCCCGC CTCGGCCTCCCAAAGTGCTGGGATTACAGGCATAAGCCACTGTGCCTGGCTGCGCCTGGCTAATTTTTAA ATCTTTGTAGAGATGGGGTTTTGCCATGTTTTCCAGGCTGGTCTTGAACTCCTGGACTCAAGCGATCTTC CTGCCTCAGCCTCCCAAAGTGCAGGATGACAAGCGTGAGCCACCTTGCCTGGCCATATTATTAAATTATC ATGAGTTTAAGTTTAAGTAGCCACAAGTGGGCTGGGTGCGGTGGCTCATGCCTGTAATCCCAGCATTTTG AGAGGCCAAGGTGGGCGGGTTGCCTGAGGCCAGGAGTTCAAGACCAGCCTGGCCAACATGGTGAAACCCC ATCTCTACTAAAAATACAAAAAAATTAGCTGGGCGTAATGGCGTGTGCCTGTAGTCCCAGCTACTTGGGA GGCTGAGGCAGAAGAATCGCTTGAACCTGGGAGGCGGAGATTGCAGTGAGCCGAGATCGCACCACTATAC CCCAGCCTAGGTGACAGAGCAGCCCTCTGTCTCAAAATAAGATAGCCACAAGTGGTTGGTGGCTGCCACA TTAGATGGTGCAGGGTTTTTGTTTTGTTTTGTTTTTTGTTTTTTCGAGGTGGAGTTTTGCTCTCATTGCC TAGGCTGGAGTGCAATGGCATGATCTTGGCTCACCACAACCTCCTCTTCCTGGGTTCAAGCGATTCTCCT GCCTCAGCCTCCCGAGTAGCTGGGATTACAGGCATGCACCACCATGCCTGGCTAATTTTGTATTTTTAGT AGAGACAGGGTTTCTCCATGTTGATCAGGCTGGTCTTGAACTCCCGACCTCAGGCGACCCACCCACCTCG GCCTCCCAGAGTGCTGGGATTACAGGTGTGAGCCACCATGCCTGGCTAAGATGATGCAGTTTTATCCAGG TGGAGATGAAGAAATAGTCAGGGAAAGGTTGAGAGGCTGCATATTGTAGACAGATTGGATTACTGGGTTC ACTGGGGAAGATTGGATTAGAAGGAGGAGTGGGGCTGCTTTACTTGTCCCCGACTTCTTGCCCCTGCTCT GCCCACTCCTTCATTGAATACCCTGCTGCCCTGCAGATGTGTTTGCCTGATTTTCACCTCCCTTCCTGTC TCTGTTATCATAGCAGACGTTTTAGTGCTCAGGGAAAGGAGGAGGAAGGAAACTCAGATTGTCAAGGAAT TGTGAGTCAGTTTCTCAGCCACTACCCCAGGCCTGGGCTTGGCTAAGTCATTTCACCTCTCTGACCCTAG CTAGTGGGGTGAATAGAGTCCCTACCCTGTTGGAAGTCAGGAAGCCCCTGGAGCTCGCTCTGTGCTAATT ATCGGTGACTATTTCTGTGACCCAGCTCTTCAGGGGCAGCCTGTCTGGGGGTTCCAGTGCCCTGTGCAGT ATCTCCAAGTGGTAGGTACTCAGTGTATGTATTAGTCCGTTTTCAGGCTGCTAATAAAAACACACCCAAG ACTGGGTAATTTATAAAGAAAAAGAGGCTTAATGGACTCACAGTTCCACATGGCTGGGGAAGCCTCACAA ACATGGCGGAAGGCAAATGAGGAGCAAAGTCACATCTTACATGGTGGCAGGCAGACAGAGTGCTTGCAGG GGAACTCCCCTTTATAAAACCATCAGATCTCGTGAGACTTATTCAGTATAATGAGAACAGCACGTGAAAG ATCCACCCCCATAATTCAATTACCTCCCACTGGCTCCTTCCCACAACATGTGGGAATTATGGGAGCTATA ATTCAAGATGAGATTTGAGTGGGGACAGAGACAAACCATGTCAGTGTGTATTGTGGGATGAATGGAGATG GTCATTACAGTCTTCTAAGTGTATGGGTCCATCTCTTACTTGCTAGTGTGTTAAGAAACCTGGCCTCCTT TTTCACATCTTGAGGCACTGAATGGTTTACAAATCCAACTCTAATTTTTTATTATATTTAATACACCAAT AGTGCAAGGCCTTTATTGGTAGTACTCTCCTATTACAGATGGAGAGACTGAGGCTCAGAGAGGTGAGGTC TGAACTTGGAGCTCTGGACTCCAAAACCCAGTTTCTTTTCATGGTACCAGGCTGCCAGGAGGAGAAAGGA TGGAGCTTAGATTCAAGTCTTGCAACATTCTTCTTAGTCCAGTATTGGCTTATTTTGTTTTATATTTTTT TGAGACGGAGTCTTGCTCTGTTACCCAGGCTGGAGTGCAGTGGCGTGATTTCTGCTCACTGCAACCTCTG CCTCCTGGGTTAAGCGATTGTCCTGCCTCCCCCTCTCGAGTAGCTGGGACTACAGGTGTGTGCCACCGTG TCCGGCTAATTTTTATATTTTTAATAGAGACAGGGTTTTGCCATGTTGGCCAGGCTGGTCTCGAACTCCT GGCCTCAACTGATCCACCCACCTCAGCCTCCCAAAGTGCTGGGGTTACAGGCGTGAGCCACCATGTGTGG CCGGGCAGGTGATTTTTCTTGTCTTTCGCCTCTTTCCACTTCAGTCCCCCTGGCCATCTTTCCCTTCCTT GAATGTGCCTCCTCCCACCTGGTGGCCTTTGTAGGTATGAGGTCCTTCAGATGATGGCTGACATGACACT TCCTCAGAGAAGCGTTCCAGACCCCAAACACCAGGTCTCTGTCTGTGAAACAGGGACAGTGATACCTGCC TAATCTGCACGCCTTTCCCTTCTCACGAGATATTCTGGGAAGGGGGACTCAACTCTTTGCTCTGTTTGAG GGCAGAGTGCCTTTGAGCTCAGGAGAGAGTGGGTTTGGGTGGCCTTAGCTACCCTAGATACGGAGGACTT GGAGTTAACTGGCACCATCCACAAAGCCTTGCATGCACTGGACCTGAACAAGTTGCTTAGCCCTTGAGGC GGCGCCTCAGCTACCACCTGTCTTTGATGGAGTTATGATAACAGTGCCTGCCCCGTCTGGATGCCTTATG GGTTCAGTGAGCACATAGGTGTAAATAAAGTGCTTTGAGTGGCACCTCAGCATGTAGTTATTCTCTGATT GACCTATAGCAGCCATGCCAGTCTTCAGGGTCCCAGGGCGCCAGGCTTTCTTCTCTTGCCTTGGAGCCTT GGTTTTTCCCTAGGACTGAAGTGTTCTGACCCCTTGGCTGAACTCCCCCTTCTTTAGGAAGCTTTCCCTG GTGTGCCATCTGATGCTGGTGCTTCCTGGAGGGGTACTATCTGATCCTAGCTGGTGAGGCATTCCTGCCA GAGCTGCGGCAGGTGCTTTCCCCGCCTCTCCACCAGCCTGTGAGGTGGATGCCATCCCCACGAGGGCACG CAGGTTCACAGAGACTGGCTCCTGTCCAAGGCCGCGTGGCTGGAAAGAGACAGAACCAGATTCAAACACC AGCAGTTTAACCCTAGAGACCCTCATCCTACCTCCTATGTGGGTAACCACTATACATCCTGCCTCCTCTG AAATCTCCCGTTTTTTTTTATTTTAAAATTTTATGTGAGTATTTACTTATTTATTTGCTGCTGTTGTTAT TGTTTTGAGACAGAGTCTTGCTCTGTTTTCACCCAGGCTGGAGTGCAGTGGTGCGATCTTGGCTCACTGC AACCTCTGCCTCCTCGGCTCAAGCGATTCTCGTGCCTCAGTCTCCCGAGTAGCTGGGACTACAGACATGC ACCACCATGCCTGGCTAATTTTTGTGTCTTTAGTAGAGATGGGGTTTCGCCATATTGGCCAGGCTGGTCT TGAACTCCTGGCTTCGAGTGAACTGCCTGCCCTGGCCTCCCAAAGTATTGAGATTATAAGCATAAGCCAC TGTGCCCGGCCAAAATTTTATTTATTTATTTATTTTTTTGAGATGTAGTCTTGCTCTGTCACCCAGGCTG GAGTGCAGTGGCACAATCTCGGCTCACTGCAAGCTCTGCCTCCCAGGTTGACGCCATTCTCCTGCCTCAG CCTCCCGAGTAGCTGGGACTACAGGCGCCCGCCACCACGCCCGGCTAATTTTTTGTATTTTTAGTAGAGA TAGGGTTTCACCTTATTAGCCAGGATGGTCTCGATCTCCCGACCTCATGATCCGCCCGCCTCGGTCTCCC AAAGTGCTGGGATTACAGGCGTGAGCCACCACGCCCAGCCTAATTTTATTTATTAATTTATTTGAGATGG AGTCTCACTCTGTCACCCAGGCTGGAGTGCAGTGGTGCGATCTTGGCTCACTGCAACCTCCACCTCCCAG GTTCAAGCGATTCTCCTGCCTCAGCCTCCTGAGTAGCTGGGACTATAGGTGCGTGCCACCACGCCTGGCT AATTTTTGTATTTTTAGTAGAGATGGGGTTTCACCATCGTGATCAGCCTGACAGGCTGGTCATGAACTCC TGACCTTAAGTGATTCACCTGCCTCAGCCTCCCAAATCTGCTGGGATTACAGGCATGAGCCACCGCACCC AGCCATATTATTTCTGTATTTTCATTTGGCTTACCTGTCAACTTGACACTTTTTTGTTTTTTTAGGCTAG TCAGGTGAAGCAATGTGAGTAAGATCACCTGTCTTGATTATAACTTGTGTGTTCAGTGTTTGTCATTCAT CCCTCCCTGTCTCTAGCCTTCAGTTCAGGGCATGATTTGGAGCAAATGTTCAGTATCTGTTTAACAAGAA CAATCATGAGAAATACTTACTCACTACTTGTGTTTATGAAACATTATGTGCCAGGCACTGGGCTGAGCAA TCCACACAGGTCAACTCGGTTAATCCTCATGACAACCCCTGAGATAAGTACTTATACCACCCTCGGTGTA CACAGGAGGAAACTGAGGCTCAGGGAGTTTTTCTTTAAAAATTTTTTCTTTTTTTTTTCCTTGAGACAGG TCTTACTTTGTCACCCAGGCTGGAGTGCAGTGGTGTGATCTTGGCTCACTGCAGCCTCTTGGGCTCCAGC GATCCTCCCACCTCAGCCCCTCAAGTAGTTGGGGAGTACAGGTGTGCACCACCATGCCCAGCTAATTTTT TGTAGGGATGGGGTCTTGCCATGTTATCCAGGCTGGTCTTGAACTCCTGGGCTCAAGCGATCCTCCCTCC TTGGCCTCCCAAAGTGCTGGTATTACAAGTGTGAACCACCACACCTGGCCTTAAATTTTATTTATATATT TATTTTTGTAGAGACGAGGTCTCACTATGTTTCCCAGGCTGGCCTCGAACTCCTGGACTCAAGTGATCCT CTTGCCTCAGCCTCCAGAGTAGCTAGAATTACAGGCGTCTGCCACTGCACTTGGCTCAGGGAGTTTAAGT CACATAATCAGGCAGCGGTCTGCTCAGTTAGAGTCCATGCGCTTAGCCATGGTGCCTTCAAGTGACTCCA CCAGGGTCACCCCAGTACTTCCTGGGCAGACCAGACCATCCAGAGCGGGCAGGTTGTGCTTTCCTGCATG GTGGGAGAGGACGTGGCATGAAGCTTTGTGTAAATCTGTGCAGCCTCTGCCATTGTAAATCACTGGCCAC CGGGACAGACTCCCCCACCCCCTTCCAAAAACTAGAGGAACAGATGGGTGGAGTCGCATCCTTCCTCTGC AGGCATTTGGCCACCCACTCCCATTATGGAGCATTTCCTCAGGACCAGGCACAGCGTGGAGCCCTTTGCA TAGCTCACTGAATTGGGGCAGCAACCCTGGGGCTGGGGACTACCATTATCTCCACCAGCCCAGCAAAGAG GGGAGGAGGGTACAGCCGAGACCCAGCTGCAGTATGTGGAGCACACTGGGGTGCCGTGAAGATAGCTGTC CAGCCTCTAGAGGCTGACAGTCCTGCCCTGACACAGTGGTTTGTTCTCAGACTCTGGCCTCCCCTCTTAG TGCCCGTCTGAAGACTTCAGCCTTCGGTCCTCTTCCATCAGCATGCCGTCTCCCCTGTGCCTCAGTCTCC CTCTCTGGAGTATCTGCTGGGGCCACAGTTTGGTTTTATTGTTCTTTGAGACAGGGTATCACTTTGTTGC CCAGGCTGGAGTGCAATGGTGCAGTCATGGCTCACTGCAGCCTTGACCTCCTGGGCTCAAGCCATCCTCT CACCTCAGCCTCCCGCAACTCCAGTATCTGGACTACATGTAAATGCCACCATTCCCAGCTAATTTTTTTT TTTTTTTTTAGATAGAGTCTCACTCTTGTCACCCAGGCTGGAGTGCAATGGTGCCATCTTGGCTCACTGC AACATCCGCCTCCCAGGTTCAAGCCATTCTCCTGCCTCAGCCTCCCAAGTAGCTGGGATTACAGGCACCT ACCATCATGCACGGCTGTTTTTTGTATTTTTAGTAGAGACAGGGTTTCACTATGTTGGCCAGGCTGGTCT TGAACTCCTGACCTCAGGTGATCTGCCTGCCTCGGACTCCCAAAGTGCTGGGATTACAGGCGTGAGCCAC CACGCCCAGCCTTCCTGGCTAATTTAAAAATTTTTCAGAGACGAGGGTTTTGCCTAGGCTGGACTCACTA TGTTGCCTAGGCTGATCTCGAACCACTGGCCTTAAGTGATCCTCCCACCTCAGCCTCCCAAAGTACTGGG ATTACAGGCATGAGCCGCTGCACATCGCCACAGTTTGATTTTAGTATCCACTTTAAGGTGCAGTTAGTTC TTCCCAGCTCCTCTTTTCCCTATCTCATACAGTGTAGTCACTTCCCTTTCTCCCACTTCTCACCTTCCTA GATTTTGTTTTTCTCTCTCTTACCAAGTTTTGAGTATGTAATACGTCCCAGATCGGTGCTGAACCCCTGG TGTGAGTTAACTTAGCAACTTTTCACGTGGTGTTCTGCAGCCTTCTTACAGATAAGGAAATTCAGAGAGG TGAAGTGTTTTTGCAGAGAGCCACACAATGAGCTAAGAAATTAGAACCCAGGGCAGTTGAACTCCAGAGC CAGGGAACTTAACAGCCCATTCATGCATTCACTCAGGAATTCCCTCTTGAGTGCCTGCTGTGAAGGCAAC CTGGACGCTGTCTCTGCCTTCCTGGGATTGTGGTGTGTGTGGGAGACAGACACGAAACAAAGCAATCTTC TAGGTCAGTGTCTGGCTATGCTGGGTACTCAGAAGGGGGAAGCACTGTGCTGCAAGAGGCCGGCTGTTTC CTCCTCACAAGGGGAGGCCTGCAGTGACATTGCCAGGCCTGAATCTGCCCTGCCATTGGGAGTGTAATTT CCTCACGACTACAAATGCAAATAAATACACACACTGAACATGCTACCCCGCTAGAACTGTGGACAGCTTG TTCACTGCAGTTAAAGGAAGACGGAGGGACACATTTGAGCACGCATGTGTGAGATCCAGCTTGTGGCAAA CCCTGCCATTCTTTAACATCTGTGGGAAGTGAAGCCACCATTACTGACCTCGGAGGAATCCCGGGAGTAG TGGGAAGAAAAGTTGCAGATGTTTGAAAATCAGGCTGCAGGGGCAGTTGGGGTGAGGAGCATGGATGTCT AGGAGCCTGAATCTCAGCGTTGGAAGCCCAGTTCTGATGTAATTTTTTTTTTTTTTTTTTTTTTTGAGAC AGGGTCTCACTTTGTCCCCCAGGCTGGAGTGCAGTGGCACAGTCTCAGCTCACTACAGCCTCATCCTTCC AGGTTCAAGCAGTCCTCCTGCCTCAGCCTCCCAAGTAGCTGGGACCACAGGCATGTGTCACCATGCCTTT CTAATGTTTGTATTTTTTTGTGGAGACAGGGTTTCTCACTGTTGCCCAGGCTGGTCTCAAACTCCTGAGC TCATGTGATCCTCCTGCCTTGGCCTTCCAAAGTGCTAGGATTACAGGCGTAAGCCACTGCCCAGCATCCC CACCTTTTTTTTTTTTTTTTTAAATTTGTGGTTTGGTGCAGGTTATTTTACCTCCCCAGGCCTCGGTTTC CTCATCTACTCAAGGGCAATGGCAGATAATCAACCTCACAAATTCCCCGAGGAGTTAGTAGGCTTGTGCC TGCCAGGCTCAGCTGGCTTACAGCAGGTGCTTCATAAGGGGGAGCTATTGCAACGCCTCGGCTGGTTCTA GGCTGCCTAGCTCCAGAGCTAAGAGTCCCAGTGGGTTCATATCCCTTTGAGCATTTATAGGCTTCTCACA GGTCTCCTGGGCTTTCTCAGCCATTCCTCATCTGACCTGAGGAGGTGTGATGTCCTTGCAGGACTCCTCC AGCCCCTCTGAGCTTTTTTTTTTGTTTGAGACAGCATGTTGCTCTGTTGCCCAGGCTGGAGTGCAGTGGT GTGATCATGGCTTACTGCAGCCTCCACCTCCTGGGGTCAAGCGATTCTCCCACCTCAGCCTTCCAAGTAG CTGGGACTATAGGTGTATGTTACCATGCTTGAGTAATTTTTAAAATTTTTTGTAGAGATGTGATCTCAGG CTGGTCTTGAACTCCTGGGCTCACCTGGGCTCAAGTAATCCTTGAGCCCAAAGTGTTGGGATTACAGATA TGAGCCACCTTGCCAGGCCCTGAGCTCCTTCTGTCTTCCATGAAGGACACACTATTCCTTGCCTTTTGTC TTTTTTTGTGTGTGTGGCAGGGTCTCTGTTGCCCAGGCTGGGATGTGTTGGTGCAATCTGGGCTTATTGC AACCTCCGCTTCCCGGATTCAAGTGATTCTCCTGCCTCAGCCTCTTGAGTAGCTGGGATTACAGGTGTGC GCAACCACGCCCAGCTAATTTTTGTATTTTTGGTAGACATGGGGTTTCACCATGTTGGCCAGGCTGGTCT CAGCCTCCCGAAGTGTTGGGATTACAGGCATAAGCCACTGTGCCTGGCCACTTTTTGTCTTTTGCATGTT CTATACACCTTGCCGAGAATGTGCTTTCCCTGCCTCCTGGTTATCCCTCAGGTTTCAGCTCTAACATCAC TTCCCCAGGGAAGCCTTACCCTCGCTTTCTTCTGCTATAGGATAATATGAACCACCATCATTGTTACTTG TTTAGTGTCTGCCCTCCCTGCTAGGCAGCAAGGACAGATATCTTGCCTGTCTTAGGTCCCCAGAACCCAG CACAGGGCTTGGAACATGTCAGGTGCTCAAATATTTGTTGAATGAGTCAGTCTGGGCTCGCAGAGGGAGC TGGGACCAGAGTAGAGTGGACACTGAAGCGTATGTAGCAGTTTGCCAGGCGATAGGGAAAGAGACCTTCT TGTAAAGCAAGCAGAGATGAGAGGGAGAAATGAGAATTGCTAAGATTGTTTTGAGCATTTGTTAGGTGGC TTACAGATGCTTTGCTGAACATTTTATTCATGTGATCTTGTTTAAGCCTCTCATTTCCATGAGGGGTTCT CCATTTTTATAGACAAGGAAGGGGACACGTGGAGAGGGGAAGTTACTTTGCCATATCACCCTCTAAGGGA TTTTTTTTTTTTTTTTTTTTTTTGAGATGGAGTCTCACTGTCACCAGGCTAGAGTGCTATGGCGCAATCT CGGCTCACTGCAACCCCCACCTCCCGGGTTCAAGTGATTCTCTTGCCTCAGCCTCCTGAGTAGCTGGGAC TACAGGCATGTGCCACCACATCCGGCTAATTTTTCTATTTTTAGTGGGTACAGGGTTTCGCCATGTTGGC CACATTGATCTCGAACTCCTGACCTCAAGTGAGATTCGCCTGCCTCTGCCTCCTAAAGGCAGTAAGGGAA TTGAACCTAGGCAGTCTGACTCTTAAGAGCTCAAAGACTTAAGCTCTGTCCTGAGTAGCTTCGCTGGTGT ATGGTATAGGGATCAGAAGAGAGCTGGTCTGTATGCCTAGAGGGCATCCTGCAGTGGGCATGTGTGTCTG TGGTCACAGTGGGAGAGAGAGAGGAGGGGGCATCTGTGGCCAGAATGGGGAGGCCTCGAATGCCAGGATG AAGAGTTTGGGCCTATGGTAATGAGAATAGTAATAGCTACCAGTTATTGACTTGCCAGCCACTTGATTGA GTCATTTAACCTCACAACAGTCCTATGGGATAGGTGTTAACTGTTTTCATCCCAGTTTTTCAGATGGGGA AACTGAGACACAGAAGTTGTAGTCAGTTATCCAAAGTGTCGCAGTGAGAAAGTGCTGGAGTTGGGGCTCA GACCCTGTGAGTCAGGCCCCAGAGTTCACTGGGGCCACATGCTCAACCACCATGCCGCCTGCCTGCCGCC GGGGCTGAGCCAGCGGAAACCTGGGTGCTGCTTCTGATGCAGGTGGTCTCCTCTGCTCTCTTCCCCAGCA CCCCCCCAGGCAGCAGCAGCAGTTTTCATCTCTGGATGACAAGCCCCAGTTCCCAGGGGCCTCGGCGGAG TTTATAGATAAGTTGGAATTCATCCAGCCCAACGTCATCTCTGGAATCCCCATCTACCGCGTCATGGACC GGCAAGGCCAGATCATCAACCCCAGCGAGGACCCCCACGTGAGAGGCGGCCTCCCCCACTTCCCGTGCCC CCCACGCCCAGGCCCCTTGCCTGTCTCCTCTCTGGTCCCAACTGCCCCACGTCTATCTGTGCCTCCACCC GCAGCTGCCGAAGGAGAAGGTGCTGAAGCTCTACAAGAGCATGACACTGCTTAACACCATGGACCGCATC CTCTATGAGTCTCAGCGGCAGGTGCGTGGGGACAGGACTAGGGGCGGGGGGCTGGAATTACCTGAGGTCC CCTACCTGTGTTTGGGCCAAAGGAATGGCTCCCAAGGAGGACAGATTCTTTTTTGGGGGGGTTCCATAGA GTTCTGAGGGTTCTCTTGGGACTCTGGAGGAGAAGTGTGAGAGCAGTCCTGCCTTAGGGCAGAAGGATGG ACCTGATCACTAAAAAACACCTACTGTGTGCCTGGCTGGGGGCTCGCCTGTGTGGGGAGAGGGCAGGGAG AAGGCCTGACAGCCCTTCCTCTTGGAAATGCACAGTCCTGAGAAACAGGGTGGGTCCCCAGTGCTTCCTG GAGTGCTCCAGGGGACCGCCCTAGGCCCATGTGAAATGGGCTGTGATCCCCTGATAAATCCTAGTATCAG GGACAAGGATCCAGTCAAGCCAGTGTCAACAAAGAGGGAAGTTATTGACTCCAATGACCATACATCCAGA GGGTCCTGTTTTGGGGCACAGCTAGATCCAGGGGGTCTTCCAGGCAGGAAGTAGAGGGAAGGCGGAAGGC CAGACATGGCACATCCCAGCTATCCCACACCCCCACCTTTATAGAGCTTTCTGGGTAGTCCCACCTAGTG ACATCTGCATACATTTCCTGGGCCACTCCTAGCTGCAGGGGAGACTGAGAAATGTATTAATAATACTTTA GTCCCGGCAGTTGCTGCCTGCGGGAGATTGAGACCTCTGTTAACAGAGGAGGGGAATAGTATACTGGGAA GGCAACCAGGAGCCTCTGCCAGTAGCCCCGAGTCCTGATCCTCAGGGGGCTGGTTGCAGGCTCTTACCCA CGCTAACCTGGACAGTCCTGCCAGGCCCTCAGTACTCAGCACCGCCCACTCACTTGGCACTGGAATGTGC ATTAACTTTTAATTGGCTCCCCACTTAGAAGAAAGCACACATTCATCAGTTTCCCCCACAGCAACGGGAA AGCCAGGCCTGGGAACACATGGAGGAGGGCACCGCCGAGCCGCGAGGAGCTCTGGCCCCGGGGTGTCCCT CAGGGTGCTGGCCAGGCTGCCTTTGTTCCGCTTTACACATGGCCCTGTGTGATCTCATGTCCATCCGTAT GCCAGGGCTGCCCAGAGCCCCAGCCAGACTGCTTGTCAGAGCCCTGCTTGGCTTCTCGCCCTGGATGTCC CACAGCAAACTAATCCTGTCTGAACTTGACCTCGACATCTTCCTCCCAGGCGTGCTCCTTTGCCTCACCT AGTCCGTTTCTCAGTGAAGAGCACCACCATCCACCTGCTTGCCCACACCAGAAACCTCATCTCATCCCTG TCTCCTCCCTCCCCCTTGCTATCCCTTTCTCCCCTCTCATTCCCTCTGTCTGTAGATATTTCTTTTTTTT TTTTTTTTTTACTTTTGAGATGGAGTTTTGCTCTTGTTGCCCAGGCTGGAGTGCAATGGCACGATCTTGG CTCACCGCCTCCCTGGTTCAAGCGATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGATTACAGGCATGCG CCACCACACCTGGCTAATTTTGTATTTTTAGTAGAGATGGGGTTTCTCCATGTTGGTCAGTCTGGTCTCG AACTCCCTACCTCAGGTGATCTGCCTGCCTTGGCCTCCCAAAATGGTAGGATTATAGGTGTGAGCCACTG CACCCAGCTGTAGCTACTTCTTTTCTTTTATGTTATTTTTATTTATTTATTTAGAGACGGAGTCCACCTC TGTCGCCCAGGCTGGAGTGCAGTGGCGCAATCTCGGCTCACTGCAACCTCCGCCTCCCAGGTTCAAGTGA TTCTCCTGCCTTAGCCCCCCAAGTAGCTGGGATTACAGGCGCCCACCACCACACTCGGCTAATTTTTGTA TTTTTAGTAGAGATGGGGTTTCACCACATTGGCCAGGCTAGTCTGGAACTCCTGACCTCAAGTGATCCGC CTGCCTTGGCCTCCCAAAGTACCGGGATTACAGGTGTGAGCCACCGTGCCTAGCCTGTCTGTAGATACAT CTTTAGGAAGTGCTCAGCTGCTCAGCAGCACACTCTGAGACCCAGCCCCATCCTTTCTCTGCTTCACTGT TGTTGGTGAGTTGACCTTCGTGCTCTGCTTGTGGCCTCGTGTTCACAGCATGGCTGCTGCATGTCCAAGC TTCATGGCTGTCTGCAAGGCAGGAAGAAGTAGGGAGTGGGTAGGGCTGGCACCAGCAGCAGTGGTCTCTT CTATCCAGAAAGCAAAAGCAGACTTCCACCAAAATATCTGGCTAAAACTGTGTCCCATGGCCACCTCTGG CTGCAAGGGAGGCCAGGGACCTGAGTGCGTGTCTTTTTGAGGCTCAGGTTAGGGGATTTGGGAGAAGGGA ACTGGGCACTGGTGTGGCCAGCTGACAGGGTCTGCTGCCCCCTAGCACAGCCGACTCAGCTTCCTCAGAC ACATCCACCTGCTCCTCTCCCGCCTCCCTCTGCTACCAAGCTGGGCCTCTGCCCCCTCTCTCCTGGCTTG CTGCAATCAGCCTTGATGACTCCATCCATTTACCTCACTGCAGCCTGAGAGCAATTCTAAAACACAGGTC TGACCACATTGCTCCCTTGAGAAGACTGTCGGCAGGTTACCACTATTCTCAGAGTAAAATCAATGTATCG TTCCCTTTGTTATCTGGGTGCCATCTCCTCTCCCTCCTCATCTTTCCCCACCCCTACCACTGTATGTCCC AGCCCTTCTGGCCTCATGGTCTATCATTCCCTCTGCCTGGAACCCTCCACCCACCCCATCTTTGCGCACT GGTCCTCACCGATGCCCTTCCGTGGTGGAACAGGTGCTTCCTTTGGGCTTCTATCACAGCAACTCGATCC CTCTGGCAGTTCTAAGCAGTCTGGCAGCGTCTTCTTAAAGGCAGGAACCCCAGCATGGCCTGGCCCAGGA CTGGCCTTCAGGAGGACTGTGAATTCATGGAGGTGTTGGAAGCTGGGCAGGATTTGGATGGCTCTCTGTC ATTGCCCAGCATAACCAATTGTGGGACCCCGGTCCCCTCTACACCCCCAGGGCCGGATCTCCTTCTACAT GACCAACTATGGTGAGGAGGGCACGCACGTGGGGAGTGCCGCCGCCCTGGACAACACGGACCTGGTGTTT GGCCAGTACCGGGAGGCAGGTACGTCTGTCCGTGGTTTGGCCCTGTGGTCCCCATTGAAGTGTACACTTT AGTTTTTCTGAGTGTTCTTCCAGGAGCAGCATAGTGCCAGGAAGGTCTAAGGAGCTGGAAGAAGAGCTTT CCAAGCAAGAAAGAGACAAGCCAGGGTTAGGACTCTGGAGGGGGCAGTCTTCCCACTCTGAAGGCCAGAA AGTGTAGTGGCTCAGGGTCTGTGCTCTTAACCCTTTGTTACCAGTTGTCAGGTTTTGGGCAAGTCACTTC CCTTCTCTGAGCCTCAGTTTTCTAATCTCCAGAAGAGGGATTATGACGGTACCTGCATCCAAGGGTCGCT GGGAGGATGCAGTGAAGTCAACGTTCGCTGTGGGTGTGGCCTGTGCAGGAGACCCTGTCTGCCTGGTGCA GTGATCCCCTGGCCCCTCCTCAGGTGCTGTATCCTTCGGGGAGCAGGAGCAGGTGGAAGAACCTTGACAG ACCTGAGTGCGGTGCAAGATTAGAGGGGCCCGGCAAGCCCAGATGAGTGAAAGGAAGGAAGGGTCAAAGA CCAGGAATGAAGAAAATCATTGAGCAGGAATGAGTGCCTGGGAGCGAAGGAGTGAGCCCAGGGAGCAGTG AGTGGGGTCTTCCAGGGAGCTTGTTGGTGTGGGGCCCTGCATGGGGACTACCCTCAGAGTGTCAGCGAGC ACTGATAGGGCCAGGAAGGCATATCTTAACCCTTTGTCTTAGATGCTTGGGGCAAGTTGCTTAACTGCCC TGTGCCTCTGTTTCCTCATTCGTAAGGGGGATGGTAGCCCTTCCCAAGACAGCTGTTGAGGGCAGTCTTG GGGCAGTTGGCAAAGTGCCCTCAGCACAGAGTAAGCGCTCAGGGCCAGGGGTTGGTGTCATGATCGGGGA CTCGCCCTGGGACAGCCCTTCAGCAGGGCCAGACCACGTGGCTGTCCAGAGCCCCCATGGACCAGCATGG CTTGCAGCCTGCTCCTGGACTGTCTACTGCTCACAGCTGGACCAGGCCCTTGGCCCCACATGCTCTAGGA GGGCAAACGCCCTGTGGTGTTTGTCTAAGGTCTAGTGTCATCCGTGCGGAAAAAGATTTCCAGACACCAG GCAGCAAGCTGGGCCCCCGCCAGCTGTGCTGAGCACTGCACCTGTTTTTGCTGAAGGGTTCTCTTGTGAG GGCACCAGGCAGGACCGAGCAAGCCTCATGGGAATCATGGGAGCCGCTGAGCTCTCCACATGGGAGAGCT GGCCGCCTCTGCAAGAATGACTGTCCAGCACTGAGGGTCAGCAGAAGTGTCTGGGCAGCTGCAAATGGGA CTCATGCAGAGGCAGCATGGTGCAGGGTAAGGAGTTGAGTCACATCCACTCTAGACTTCACTTGGCAGGC CACTCACCTTGGTGACGCTGTCTGTCGTCTGTGAAGTGAGAAGAGTGGTGTTCATCATGATAGGTAGTGC CTCCCTGGGCTCTTGACACCAGAGTGCTGTTCTTTTTTTCTTCTCCTTTTTTTTTTTTGAGATGGAATCT CGCTCTGTTGCCCAGGCTGGAGTGCAGTGGCGCGATCTCGGCTCACTGCAAGCTCCACCTCCTGGGTTCA CGCCATTCTCCTGCTTCAGCCTCCCGAGTAGCTGGGACTACAGGCGCCCACCACCATGCCTGGCTAATTT TTTGTATTTTTAGTAGAGGCGGGTTTCACCATGTTAGCCAGGATGGTCTTGATCTCCTGACCTTGCGATC CGCCCTCCTCCACCTCCTAAAGTGCTGGGATTACAGGCGTGAGCCACCATGCCTGGCCTTTTTTTTTTTT TTTGAGGTGGAGTCTCACTCTGTCGCCCAGGCTGGAGTACGGTGGCGCAGTCTTGGCTCATTGCAACTTC TGCCTTCCAGGTTCAGGTGATTCTCCTGCCTCAGACTCCGGAGTAGCTGGAATTAAAGGCATGCACCACC ATGCCTGGCTAATTTTTGTATTTTTAGTAGAGATGGGGTTTCACCACGTTGGTCAGGCTGGTTTCAAACT CCTGACCTCAAGTGATTCGTTTGCCTTGGCCTCCCAAAGTGCTGGGGATTACAGGCATGAGCCACCGCGC CGGGCCAGCCAAGGTGCTGTTATATGTGCTCTTTAGCCTCGGAGACTGTCATTTCCCCTCACTGCACTGC AGAGCGAGGGCACACCGGGTGAGGTTAGGGCAGGCCCCAGTGGTGTTGCCTCATTGAGGCACCTCCCCCA TCCATGTGAGGCAGGAGAGGCAAGCATTACCATCAACTCTAAAAGCCAGGTAAGAACCTGAGTCAACAAA GGTGAGGTCATGGGCCCAGGCCACATTCTCCTAAGGAGTGGAGCCGAGTCTTTTTATGGCAGTCTGACCC AGAGACAGCTCTCGCTGTTTCCCACCCTTGGCTGTCTTCCCAGGGCTATATGTGGAGTATCAGTGGTGGC ACTGGCAGGGAGTGGCGCCCGGTGAAAAGGAGTGTTAAGAGGAAGCACGTGCCAGGTGTGGTGGCTCACG CCTGTAATCCCAGCACTTCGGGAGGCTGAGGCGGGAGGATTGCTTGAGCCCAGGAGTTTGATACCAGCCT GGGCAACATGGCGAGACCCCCATCTCTAAAAAATTAAAAAATTAGCCAGGCGTGGTGGTGCACACCTGTA GTCCCAGCTACTCAGGAAGCTGAGTGGGAGGATTGCTTGAGCCCAGAGGTTCAAGACTGCAGTGAGCTAT GATTCCACCACCGAACTCCAGTTTGGGTGACAGAGTAAGATCCTGTCTCTGAGACCAACAAGAAAAGAGG TAGCATGTGTCAAGCAAGAGCAGCAGTTCCCACTGGACCTGGAGTTTCCTGGTGCAAATCAGCCTGTGAG TCTGTATTTTCTTTTTTCTTCAAGACGGGGTCTTACTCTGTCACCCAGGTTGAAGTGCAGTGGCATGATC TCGGCTCACTGCAACCTCTGCCTCTTAGGATCAAGTGATCCTCCCACCTCAGCCCCCTGAATAGCTGGGA CCACAGGTGCACGCCACCACACCTGGCTAATTTTTTTTTTGATTTTTGGTAGAGACGGGGTTTCGCTGTG TTGCCCAGGCTGGTCTCAAACTCCTGAGCTCAAGCAGTCCACCTGCCTCACCCTTCCAAAGTGCTGGGAT TACAGGCACGAGCCACTGAGCCTGACAAGTTTGTACTTTTAGCACGTTCCCCTGCCCCTGCCCAGTCCTT CTCACATGGGTGGACCTAGTACCACATTCTGAGAAAGCCTGATTCCAAGGTCCTGTATCAGTCCCTTGGA CCTTCTTTGACCCTCTACAAGACCTTTCTTTCCCTCCTTAACCAGAGCAACTCCTGTTTCTATCTGTTAC ATATGCAGCACAGCCACATCTTGTGTGGATTTGTATTATGTCCATTCAAAAGCATGTGTCAGAAAATACC AGTAAACCTGTATTAAAGTTGGATGTTGAAGTAGTGCTAACCACCCTCAACTCTAACTAAAATATCAACA AGTGGGCTGGGCGTGGTGGCTCACACCTGTAATTGCAGCACTTTGGGAGGCTGAGGTGGGTGGATCACCT GAGGTCGGGAGTTTGAGACCAGCCTGACCAACATGGAGAAACCCCGTCTCTCCTGAAAATGCAAAAATTA GCTGGATGTGGTGGCACATGCCTGTAATCCCAGCTACTCAGGAGGCTGAGGCAGGAGAATCGCTTGAACC CAGGAGGCAGAGGTTGCAGTGAGCCAAGATTGCGCCATTGCATTCTGGGCAACAAGAGCAAAACTCCGTC TCAAAAAAAAAAAAAGAAAGAAAATTAGGTAGATCTAGTGGTGCACACCTGGAATCCCAGCTATCTGGGA GGCTGAGGCATAAGAATTGCTTGAACCTGGAAGGTGGAGGTTGCAGTGAGCTCAGATTGCGCCACTGCAC TCCAGCCTGGGTGGCCAAGCCAGACTCTGTCTCAAAAAAAAAAAAAAAAAAAAAAAAAGGTAACTGCTGT GTGTAATGTGATCTCCATTAAATTTGTATCTAAAGAGCGGGTTCTGCGGTAAAGAAAGGATTTGGAAAGC ACTGTACTAGAGAGCTCCCTCTGAATAATGTTCCCGGTCTGAGTGCTTGCAGCATTGATCCACAGCGCTG CCCCTAAAGTGTTGGTGTGAAGGTTGTCCCACTCTTCAGGCGGGGCAAAGAGCTTGTCTGAGGGCAATCA CAAACCCCCTTCTGTCTTCTAACTTCGGAGGAAGGGCCCCCTTAACCTGGAGCGGTTCCCTTTGATGGGG AGGTGGGTGTTCACCAGAGGTTTTGTTTGAAGAAAAGGTTTTACTGCCATACATGGGTTAGAGTACTTCT GTAGTCCAGAAGTTGTAAATTAGTGGTCTATGCTGTTATTTGGTTCATAATGATGATTTTTTTTTTTTTT CGAGACAGGGTCTTGCTTTGTAGCCCAGATTGGAGTGCAGTGGCACGATCTCAGCTGCCTGCAGCCTTGA ACTTCTGGGCTGAAGCAATCCTCTGCCTCAGCCTCCCAAGTAGCTGGAACCACAGGCACACATCACCATG CCTGGCTAATGTTTTGATTTTTTTTTTTTTTTGTAGAAGCGAGGCCTCACCATGTTGCTCAGGCTGGTCT CCAACTCCTGGGCTCAAGCGATCCTCCAACGTCAGCCTCTCAAAGTGCTGGGATTACAGGCATGAACCAC CATGCCTGGCCATAGTAATGATTTATGGTTAGAATATTTCTTAAAGGTAATTGAATTAGTTGAAAGCACT TAAATACCAGACAATATCTCACTAAGAGAAAGAAAGAAAAAGGCTAGATTTCTGCTTTCTTTTGAAAAAT CAGATTGGCCTTGCTGGGCAGAGTCAGTCAGTCTGAACATCAGTCTTCCTCTTAAAACAAGCCTGAGCTT TCCTGTCTGCCTGCCAGCATGCTGCAGGTCACCCACAGGGCTGAACTGTCCCCCTGTACTGCCCACTCGG CTAACCATTGCCTCCTCCCCTCCTAGGTGTGCTGATGTATCGGGACTACCCCCTGGAACTATTCATGGCC CAGTGCTATGGCAACATCAGTGACTTGGGCAAGGGGCGCCAGATGCCTGTCCACTACGGCTGCAAGGAAC GCCACTTCGTCACTATCTCCTCTCCACTGGCCACGCAGATCCCTCAGGGTGAGGATGCATGCCCTGTACC TTGCACATGTGCAGACCAATGTCACACCCCTGTCCAGGCCTCAGCTCTTTTGCCTGCCTTCTGGGTGGAA TTCTGGGTTGGTGACACCACTAGAGCCCTGGTCTGTGCTCCAGACTTCTTCTTCTTATTTTTTTCTTTTT TGAGACGGAGTCTTGCACTGTTGCCCAGGCTAGAGTGCAGTGGTGCTATCGCAGCTCACTGCAGCCTCCT TCTCCCAGCTTCAAGCAATTCTCCTGCCTCAGCCTCCCGATTAGCTGAGACTACAGGTGTGCACCACCAC GCCCAGCTAATTTTTGTATTTTTAATAGAGACAGGGTTTCACCGTGTTGGCCAGGCTGGTCTCAAACTCC CGGCCTCAGGTGATCCACCCGCCTCAGCCTCTCAAAGTGCTGGGATTACAGGCGTTTAAGCCATTGTGCC CAGCCCACTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTGGTCTGAGACGGGGTTTCACTCTCGTCAG CCAGGTTGGAGTGCAATGGTGCAATCTCGGCTCACTGTAACCTCCACCTCCCAGGCTCAAGTGATTCTCC TGCCTTAGCCTCCTGAGTAGCTGGGATTATGGGCATATGCCATTGTGCTTGGCTAAATTTTTGTATTTTT TGTAGAGATAAGGTTTCACCATTTTGGCCAGGCTGGTCTTGAACCTGAGTTCAAGTGATCTGCCCACCTT GGCCTCTCAAAGTGCTGGGATTACAGATGTGAGCCACTGCACCTGGCCTGTGTTCCAGACTTTGAATGCA CCTCTTGTCTGGGACCCTTCAGAAGAGGGCTCTGTTGCTGTCCCCACCCCATTCAGGGGCCTGAAGCCTG TGTGACCACACTCTGGATTTCCCAACCACATGCCTACTGCATTTGTCTGCTCACAAACATAGCCAACGTG TGCACCAGGTTCCACTGTGCCAATGCTTCACGTTCATCATCTAATAAGGACCCTCATTGTGGCCATGGGG ACAGAGGTTATTATTTGCTCTTGTTCCTGTTTTCAAGAGCAGGATGCCCGTGTTTTGTGTGTGTGTGAGA GACAGCAAGTGAATGGGAAAAAAAAAAGTGCAGGAGCCTGGCCAACATGGCAAAGCCCTGTCCCTACTAA ACATACAAAAATTAGCTTGGCATGGTGGTGCACACCTGTAATCCTAGCTACTCAGGAGGCTGAAGCAGGA GGATTGCTTGAACCTGGGAGGCAGAGTTTGCAGTGAGCTGAGATCGTGCCATTGCACTCTAGCCAAAGTG AGATCCTGTCTCAAAAAAAAAAAAAAGGAAATTGAAGTCAAAGAGGGAAGTCACTCGCTAACGGTCATGT GGCACAGAGGGAGAGGAGCAGGGACTCAAGTCATTGACTGTGTACCTCCAGAGCCTGGGTTCTTGGCCCT GACCTTTGTCTGCCTCAGTCCTCAGAGTCAAGTAAGCTTCCCCAAAGCTTACCGTAGGTGCCCTGAAGTC CCTTCCCTTATAAGAGCTTTTTTGGGAAGCAAACCCACTGGGTGCCAGGCCTGCACCCTCATAGTGTGGA GAACAAGGAATCGGAGCCCCTTCCTGTCCTCCGGGGCCTGTAGCCTGATCTAGGGTTGGTCTGGGCCCTG GCTTCTTTGCCCTAGGGCAGCTGAGATGCATGAGTTTGTGTCTCTCCAGGCCTCAGCACTGTGCCCAGCA CAGCAGGAGGCTCCACACCCCTTAGCTCATAGTGTTCTTTTGTTGAGGAACAAGAAGCAGTTTGAGCCTC TTAGGTGGGAGGTGGGCAGGGAAGCTTTCTCAGAGGAGGGGGCATTTAGGGGGCATTTGAGCTAAAGGTA ATAGGGTTTCCACAAGGCTGGGGCGTGGCCCTAACCTTCCCTCTGGGTCCCTGCTAAGTCACTTCAAATA CACGAAGTTCCTGCCATGTGCCGGTGCCACTCCAAGTGCAGGGAACAAAAGCAACGCAAACCTCAGCCCT CCTGGTGCTGCCATTGTGGTGGGGGAGACGGACAGTAACAGAGATGGAGAGGGAACTCCTGGAGTATATG AGGGTGGGGGTCCTGTAGGGAGCAGCCAAGCCAGCCGGGTGTGGTGCACTGTAGGGGTGGCTGGGGTCCG TCACTGGAGTGACACTGAAGTATGGACCAGAGGATGTGAGGGGGGAGCTGTGTGGTGTCTTGAGGCAGGT GTGAGCCTGGCGTGTTTGAGGAGCTGGGAGGAGCCCAGAGGGGCAGGTGTGGAGTGAGCAGGTGTGGAGT GAGCGGGTGTAGGGTGAGCAGGTGTGGGGTGGTTGGAGGTAAAGTCCAGGAGGTGGTGGGTGGGGGTGCA GATGGTGCAGGTTGGGTGGGGCCTCAAGGCCTTTGCCTGTTGCAGGGATGTCGACTTTTACTCAAAGTGG GACAGGAGCCGTGGGTGGGGAGGAGTCTGCTCTTCCTTGGCCTGGCTCACCTCTTCATGGAATCCGCGGG CTGCCCTGTGGATAAGGGATTGGGCAGTGTGTGAAGGGCTAGTAAGGAGGCTGCTCAGTAACTTGGGCTT GACCAGGGTGGTGCAGAGGAGGAGGTAAGAGGGGTTAGGTTCTGAAGGTGGAGTAGATGTGGAGAATGGC GGGAAGTTTGGCTTGGAGATGATACTGGACTCTTCAGCCTGAGCAGTTGGAAGGGTGGAGTTGCTTTCAG CTGAGCAAGAGGAGACCTGGGTGGGCAGATGCTGGGGGGCATCAGGAGCTGAGGTGTTTCCTTTCCCCTT GAAGCCTGGTGACTGCTGGCCTGAGCCACGCTTGAGCCGTGGGTCATGTGAGTGTGAATGAGTGTGAGTG CATGTGAGTCTCCGCCCCTGCTCACCACCCTCTCATCCCCTGCAGCGGTGGGGGCGGCGTACGCAGCCAA GCGGGCCAATGCCAACAGGGTCGTCATCTGTTACTTCGGCGAGGGGGCAGCCAGTGAGGGGGACGCCCAT GCCGGCTTCAACTTCGCTGCCACACTTGAGTGCCCCATCATCTTCTTCTGCCGGAACAATGGCTACGCCA TCTCCACGCCCACCTCTGAGCAGTATCGCGGCGATGGCATTGGTATGGGCTCTGCTGGCTGCTCCCCACC CCGCTGGGATCATCTCCTTCCCTCCCCAATCCTGCCACCTTCCTGCCACCCCTACCCTCCTTCCTGGTTC TCGTCCTGTGTCCTGTGGCGTCTGGCACTTGGTCAGCCACAGGAGTTGAGGTCCTGAGCACTCAGCCTTG CTCTCTGTCCTCTCCCTGCTCGTCCCCTTGGCCTCGTGCATGTTCCTTATCTCAGCCCTGGCCTGACCTG CCTTCTCTGTGTCCCCACAGCAGCACGAGGCCCCGGGTATGGCATCATGTCAATCCGCGTGGATGGTAAT GATGTGTTTGCCGTATACAACGCCACAAAGGAGGCCCGACGGCGGGCTGTGGCAGAGAACCAGCCCTTCC TCATCGAGGCCATGACCTACAGGTGCCTGCCGCTCCCCCCGTCAGCACCCCCACAGCACTGACAGCCACC GTAGCATCTTCCTCATATCGATCACTGTCTCCAAAACATGGCCTTATCACCTGATGTTGCATCTCCCCCT TGCCTTTATTCCGTTTCCACTCCTCCTTCCCTAGTTCATCCCCCATCCTCCCTCCTGACCCCCACTCCAG GGAGCCCACACTGACCTGGGGCCCCTTGCCCCTGTGCAGGATCGGGCACCACAGCACCAGTGACGACAGT TCAGCGTACCGCTCGGTGGATGAGGTCAATTACTGGGATAAACAGGACCACCCCATCTCCCGGCTGCGGC ACTATCTGCTGAGCCAAGGCTGGTGGGATGAGGAGCAGGAGAAGGCCTGGAGGAAGCAGTCCCGCAGGAA GGTGAGGGTGCCCCGCCCGGGAGGGTGTGCTGGGGGCTGCTGCGGCCTGCAGAGCTTGGGAAGGATTTGT GGAACACCGAACTGGGAGGCTCAGGGATAACCCCAGTGATGTCTCAGATGTGGCCTGTGGAGCCAGGCTG CTGGGGCCATGTGTGTCCTGGCTCTGTGTCCTTGGCATGTTGCCCTCCACTTCCTTGTCTTTGAAAGGGG ATGCTGGTGGTGCCCATTTCAGAAACTGGTTTGAGACTGGGCATGGTGGCTCACACCTGTAATCCCAGCA CTTTGGGAGGCCGAGGTGGCAGATCACTTGAGGTCAGGAGCTTGAGAACAGCCTGGCCAAACATGGTCAA GCCCTGTCTCTACTAAAAATACAAAAATTAGGGCTGGGCGCAGTGGCTCACGCCTGTAATCCCAGCACTT TGGGAGGCCAAGGCGGACAGATCACCTGAGGTCGGGAGTTTGAGACCAGCCTGGCCAACATGGTGAAACC TCGTCTCTAATAAAAATACAAAAATTAGCCGGGCATGGTGCCGGGTGCCTGTAATCCCAGCTACTTGGGA GGCCGAGGCAGGAGAATTGCTTGAACCTGGGAGGTAGAGGTTGCAGTGAGCTGAGATCGTACCATTGCAC TCCAGCCTGGGCAACGAGAGCAAGACTCCATCTCAAAAAAAAAAATTAGCCAGGCGTGGTGGTGCGTGCC TGTAGTCCCAGCTACTCAGGAAGGTGAGGCAGAAGAATCGCTTGAACCCGGGAGGTGGAACTTGCAGTGA TTGGAGATGGCGCCACTGCACTCCAGCCTGGGCAACAGAGCAAGACTATCTCTTAAAAAAAAAAAAAAGC TGGTTTGAGGATTAGGTGGCAAACCGTGGTGGAGTGTACATGCCCTGCCCAGAGTCAGTGTGCCACCCTC CCTGGCCCGGTCATTAGGACCCAGGGCCCGTGCAGCCCAGTGGTGAGGGCAGCACCCGGCATAGGGCAGC ACCGTGTGTCCTGTCCCTGCCCTTCTCTGTGCCTCAGTTTCCTCATTGCTTAGCTGTCTACCTCTTAGGG CTGCTGAAAGCCTTAAATGATTCCACACACTTGGATAGCACCTGATCCCTGCTGGGATTTGAGGGTTTTC ATTACACTTCTGCTAGGATAATCATTTCCATTGTCGAGGTGGGAACACAAAGGCTTGGAGTGGTTAATTC CTTGCCAAGGCCCCGCAGGAGGAAGCAGGGTCCTGCATGGGAGGCCGGCTAGCCTGCCCACTGCCCCATG TCCCCACAGGTGATGGAGGCCTTTGAGCAGGCCGAGCGGAAGCCCAAACCCAACCCCAACCTACTCTTCT CAGACGTGTATCAGGAGATGCCCGCCCAGCTCCGCAAGCAGCAGGAGTCTCTGGCCCGCCACCTGCAGAC CTACGGGGAGCACTACCCACTGGATCACTTCGATAAGTGAGACCTGCTCAGCCCACCCCCACCCATCCTC AGCTACCCCGAGAGGTAGCCCCACTCTAAGGGGAGCAGGGGGACCTGACAGCACACCACTGTCTTCCCCA GTCAGCTCCCTCTAAAATACTCAGCGGCCAGGGCGGCTGCCACTCTTCACCCCTGCTCCTCCCGGCTGTT ACATTGTCAGGGGACAGCATCTGCAGCAGTTGCTGAGGCTCCGTCAGCCCCCTCTTCACCTGTTGTTACA GTGCCTTCTCCCAGGGGCTGGGTGAGGGCACATTCAGGACTAGAAGCCCCTCTGGGCATGGGGTGGACAT GGCAGGTCAGCCTGTGGAACTTGCGCAGGTGCGAGTGGCCAGCAGAGGTCACGAATAAACTGCATCTCTG CGCCTGGCTCTCTACCACCTCTGGTCTTTGTTTCCTGGAGTTTGGGGGTGATTTGAGGCCACCCCCAGCT TCTCCACCTTAGATAAATAAGGTCAAGGCTCTTGAGATACCTACTTCCCCCGGAAGCTTGCGCAAGCTGG AAGGTTAACTTCAGCAGACAGGATGGGGGTGGGGGGGTCCTCCAGAGATGGTCTCCTGCTCTCTCACAGA ATGGGAGAAGCCTGCTGTCCAGCAGAGTGATGGGGAGCCCAGTGGAGCTAGCCCTGCCCAGCAGGGGTGC AGGGGAGCGTCCAGGATGAAGGTCAGGGTGTGGCCAAGCCCTGCTCCCCACCACTCCAGGGCCCCACAGA TGCAAAAACAACCCCAGGCCTCAGAGTGGGGAGTGCATGTTTTTCAAAAACAAAAAGTAGGCAAAAACAG TCCACCACCCCATCTTTCCTGCCCAGGCCCCTGGCTGGGGGAGGCCAAGGAGTGGCTTAAGTTGTCCAGC TTCTGGGCCCTCCTCCCTCCCATCAAGACCTGGAAGGAGGGGCTGAGCCAGGGGCCGGCCCCAGAGGCCC AGGCCAGGTCAGCACCTCCGCCCTCCCCAATGAGAGTCAGCACTGGAGCCTTGGGTCTTGCAGTTGTTTC CAGAGCCGAATGCTGGCCTGGGGGCCCAGGGGCCGTACCAGCAGCAGGTTGCGGAAAGCACAGTGGTCCG CAGTGCGGTCTGCTGGCCAGGCTGTGAGGAAGCCTGGGTGGGCCTGGGGCACCAGGCCCAGGGCTCGGAT GCAAAGGCCAGTGTAGACGTCCTCAAAGGGGAAGGGTGCCACACGGGCTGCCGCCCGCAGCAGCCAGGGT GCCAGGCGCCCGGCAATGACGTAGCCACCCCCGCTTGCATAGGCTGGGTAGCCACCTTCGAAGAAGGACT CGGGCACATAGAAGGGTCCTCCTGGCTTCCGGAGAGGCATGGCCTGGGTAAAGACCTCACCCAGGTAGAG GCTTCGGGCCGAGGCAGGTGGCAGGGCCCGCAGGTGAGCCAGCAGGGCAGGGGTGTGTACAAAGGCATCG TCCTGAGCTCGCAAGACAAAACTCACGGTGGGGCAGTGGCGGCCCAGCCAGGCCAGCAGCAGCAGGTCTT TGAGCGTCTGGTTGAATGGGACGTCGAGGAAGTCCCAGAGCAGCAGGTCACTGTAGCGACGGCTCTCCCA GGCCACTAGTGAGTCTAGGTCAGGCCCCGCCTCACCCACCGGAGACCCTAGCAGGAAGAGCAGCCGGATC CCTGGAGCTGGACTGCCCCACGTCTCTCTCACGGCCTGTCGTTCTGCAAAGCGCCCTGGTTCTGACTTGA CGGCCAACAGCAGGTAGGGGACATCAGTATCTGAGCAGCTGGAGACTTGGCTGCCACCACCTCCAGGCAG CCACTGTGGGAAGCTCCGGCAGGCTGCTGACAGCAAGAAGCGGCGGAGGTCCTTGGGGTAGGAGGCGAAG TCAGGGATCTCGGTGGCGGCGGCGGCCCCCCAAGCCTGGCAGCCCCCCGTTTCAGTGCTGTCCCCACTGG GCAGGGACCCCAGCCGCCACTGCTGCTGGTTCCAGTAAGCAAAGGGCAGCGGGATAGTCTGGCCCAGGCG GGTGGAGAGGTTGGCAGGTAGGGTGGGCTCAGGGTTGGCTGGCGTGGGGCTTGGCGGGGTGCCCCGAGGG CTGGGGTAGGCCTTGCTGAGCCGGGACTCGGATGTCCACTCGATGTACACTTTGAGGCCCAGGAGTGTGA GCAGTGCTGACAGGCAGAGAAGGCACTTGGGGCAGCGCATGACCCGGCCCAGGGAAGGGGCGGCCGCGGG AGCTACAAGGGAGCCACAGGGGAGCCACGGAGGCCATTGGGGTGTGGGGATGGGCCTCCAGAGAGGGCCC AGCCAGGCCCCAGGCAGACAGCTTCACAATCTCCCATAGTCCCCGCCAACCCCCATAACAGATTCTCTCG GTCCCAGATCCTAAACAGCTCCCCTGACCCAGGGACCTCGTTGGTCCTTATTCCTAG
mRNA transcript
>gi|258645170|ref|NM_000709.3| Homo sapiens branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA), nuclear gene encoding mitochondrial protein, transcript variant 1, mRNA CTACGTGAGTGCCGGACCGCTGAGTGGTTGTTAGCCAAGATGGCGGTAGCGATCGCTGCAGCGAGGGTCT GGCGGCTAAACCGTGGTTTGAGCCAGGCTGCCCTCCTGCTGCTGCGGCAGCCTGGGGCTCGGGGACTGGC TAGATCTCACCCCCCCAGGCAGCAGCAGCAGTTTTCATCTCTGGATGACAAGCCCCAGTTCCCAGGGGCC TCGGCGGAGTTTATAGATAAGTTGGAATTCATCCAGCCCAACGTCATCTCTGGAATCCCCATCTACCGCG TCATGGACCGGCAAGGCCAGATCATCAACCCCAGCGAGGACCCCCACCTGCCGAAGGAGAAGGTGCTGAA GCTCTACAAGAGCATGACACTGCTTAACACCATGGACCGCATCCTCTATGAGTCTCAGCGGCAGGGCCGG ATCTCCTTCTACATGACCAACTATGGTGAGGAGGGCACGCACGTGGGGAGTGCCGCCGCCCTGGACAACA CGGACCTGGTGTTTGGCCAGTACCGGGAGGCAGGTGTGCTGATGTATCGGGACTACCCCCTGGAACTATT CATGGCCCAGTGCTATGGCAACATCAGTGACTTGGGCAAGGGGCGCCAGATGCCTGTCCACTACGGCTGC AAGGAACGCCACTTCGTCACTATCTCCTCTCCACTGGCCACGCAGATCCCTCAGGCGGTGGGGGCGGCGT ACGCAGCCAAGCGGGCCAATGCCAACAGGGTCGTCATCTGTTACTTCGGCGAGGGGGCAGCCAGTGAGGG GGACGCCCATGCCGGCTTCAACTTCGCTGCCACACTTGAGTGCCCCATCATCTTCTTCTGCCGGAACAAT GGCTACGCCATCTCCACGCCCACCTCTGAGCAGTATCGCGGCGATGGCATTGCAGCACGAGGCCCCGGGT ATGGCATCATGTCAATCCGCGTGGATGGTAATGATGTGTTTGCCGTATACAACGCCACAAAGGAGGCCCG ACGGCGGGCTGTGGCAGAGAACCAGCCCTTCCTCATCGAGGCCATGACCTACAGGATCGGGCACCACAGC ACCAGTGACGACAGTTCAGCGTACCGCTCGGTGGATGAGGTCAATTACTGGGATAAACAGGACCACCCCA TCTCCCGGCTGCGGCACTATCTGCTGAGCCAAGGCTGGTGGGATGAGGAGCAGGAGAAGGCCTGGAGGAA GCAGTCCCGCAGGAAGGTGATGGAGGCCTTTGAGCAGGCCGAGCGGAAGCCCAAACCCAACCCCAACCTA CTCTTCTCAGACGTGTATCAGGAGATGCCCGCCCAGCTCCGCAAGCAGCAGGAGTCTCTGGCCCGCCACC TGCAGACCTACGGGGAGCACTACCCACTGGATCACTTCGATAAGTGAGACCTGCTCAGCCCACCCCCACC CATCCTCAGCTACCCCGAGAGGTAGCCCCACTCTAAGGGGAGCAGGGGGACCTGACAGCACACCACTGTC TTCCCCAGTCAGCTCCCTCTAAAATACTCAGCGGCCAGGGCGGCTGCCACTCTTCACCCCTGCTCCTCCC GGCTGTTACATTGTCAGGGGACAGCATCTGCAGCAGTTGCTGAGGCTCCGTCAGCCCCCTCTTCACCTGT TGTTACAGTGCCTTCTCCCAGGGGCTGGGTGAGGGCACATTCAGGACTAGAAGCCCCTCTGGGCATGGGG TGGACATGGCAGGTCAGCCTGTGGAACTTGCGCAGGTGCGAGTGGCCAGCAGAGGTCACGAATAAACTGC ATCTCTGCGCCTGGCTCTCTACCAAAAAAAAAAAAAAAAAA
Protein
>gi|11386135|ref|NP_000700.1| 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial isoform 1 precursor [Homo sapiens] MAVAIAAARVWRLNRGLSQAALLLLRQPGARGLARSHPPRQQQQFSSLDDKPQFPGASAEFIDKLEFIQP NVISGIPIYRVMDRQGQIINPSEDPHLPKEKVLKLYKSMTLLNTMDRILYESQRQGRISFYMTNYGEEGT HVGSAAALDNTDLVFGQYREAGVLMYRDYPLELFMAQCYGNISDLGKGRQMPVHYGCKERHFVTISSPLA TQIPQAVGAAYAAKRANANRVVICYFGEGAASEGDAHAGFNFAATLECPIIFFCRNNGYAISTPTSEQYR GDGIAARGPGYGIMSIRVDGNDVFAVYNATKEARRRAVAENQPFLIEAMTYRIGHHSTSDDSSAYRSVDE VNYWDKQDHPISRLRHYLLSQGWWDEEQEKAWRKQSRRKVMEAFEQAERKPKPNPNLLFSDVYQEMPAQL RKQQESLARHLQTYGEHYPLDHFDK
Neutral mutations
Disease causing mutations
Several disease causing mutations are reported in OMIM. Following table summarize the reported allelic variations:
| ID | Variant type | Mutation detail | Cause | Severity |
|---|---|---|---|---|
| 1 | substitution | TYR393ASN | MSUD type 1A | classic |
| 2 | deletion | 8-BP DEL, 887-894 | MSUD type 1A | classic |
| 3 | substitution | GLY245ARG | MSUD type 1A | intermediate |
| 4 | substitution | PHE364CYS | MSUD type 1A | intermediate |
| 5 | substitution | ARG220TRP | MSUD type 1A | classic |
| 6 | substitution | GLY204SER | MSUD type 1A | classic |
| 7 | substitution | THR265ARG | MSUD type 1A | classic |
| 8 | substitution | CYS219TRP | MSUD type 1A | classic |
| 9 | deletion | 1-BP DEL, 117C | MSUD type 1A | classic |
References
branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA)
RefSeqGene of branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA)
2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial isoform 1 precursor (Homo sapiens)
