Difference between revisions of "BCKDHA"
From Bioinformatikpedia
(Created page with "==Summary== The gene BCKDHA encodes the E1 subunit of the human branched-chain alpha-keto acid dehydrogenase complex (BCKDC). It locates on chromosome 19 and has 34,217 bp. ==…") |
m (→Disease causing mutations) |
||
(22 intermediate revisions by the same user not shown) | |||
Line 1: | Line 1: | ||
+ | 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. |
||
− | ==Summary== |
||
− | The gene BCKDHA encodes the E1 subunit of the human branched-chain alpha-keto acid dehydrogenase complex (BCKDC). |
||
− | It locates on chromosome 19 and has 34,217 bp. |
||
==Reference sequence== |
==Reference sequence== |
||
+ | |||
− | {{{>gi|260593636|ref|NG_013004.1| Homo sapiens branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA), RefSeqGene on chromosome 19 |
||
+ | * [[#Genomic_sequence|Genomic sequence]] |
||
+ | * [[#mRNA_transcript|mRNA transcript]] |
||
+ | * [[#Protein|Protein sequence]] |
||
+ | |||
+ | ===Genomic sequence=== |
||
+ | <nowiki>>gi|260593636|ref|NG_013004.1| Homo sapiens branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA), RefSeqGene on chromosome 19 |
||
GGCAGCTGGTAGGGAGGAGCTGGGGGGGTGATTTTGACAAACTGGGCACCACTCAGAGGTTCAGCAGGGC |
GGCAGCTGGTAGGGAGGAGCTGGGGGGGTGATTTTGACAAACTGGGCACCACTCAGAGGTTCAGCAGGGC |
||
CCAATTACCAGGCAGCCCAATCTTCGGCCTCAGGATCACTTCGAGTGTGGCCTTGTTGAAAATCTCTTTG |
CCAATTACCAGGCAGCCCAATCTTCGGCCTCAGGATCACTTCGAGTGTGGCCTTGTTGAAAATCTCTTTG |
||
Line 493: | Line 497: | ||
AGCTACAAGGGAGCCACAGGGGAGCCACGGAGGCCATTGGGGTGTGGGGATGGGCCTCCAGAGAGGGCCC |
AGCTACAAGGGAGCCACAGGGGAGCCACGGAGGCCATTGGGGTGTGGGGATGGGCCTCCAGAGAGGGCCC |
||
AGCCAGGCCCCAGGCAGACAGCTTCACAATCTCCCATAGTCCCCGCCAACCCCCATAACAGATTCTCTCG |
AGCCAGGCCCCAGGCAGACAGCTTCACAATCTCCCATAGTCCCCGCCAACCCCCATAACAGATTCTCTCG |
||
− | GTCCCAGATCCTAAACAGCTCCCCTGACCCAGGGACCTCGTTGGTCCTTATTCCTAG |
+ | GTCCCAGATCCTAAACAGCTCCCCTGACCCAGGGACCTCGTTGGTCCTTATTCCTAG</nowiki> |
+ | |||
+ | ===mRNA transcript=== |
||
+ | <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 |
||
+ | 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</nowiki> |
||
+ | |||
+ | ===Protein=== |
||
+ | <nowiki>>gi|11386135|ref|NP_000700.1| 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial isoform 1 precursor [Homo sapiens] |
||
+ | MAVAIAAARVWRLNRGLSQAALLLLRQPGARGLARSHPPRQQQQFSSLDDKPQFPGASAEFIDKLEFIQP |
||
+ | NVISGIPIYRVMDRQGQIINPSEDPHLPKEKVLKLYKSMTLLNTMDRILYESQRQGRISFYMTNYGEEGT |
||
+ | HVGSAAALDNTDLVFGQYREAGVLMYRDYPLELFMAQCYGNISDLGKGRQMPVHYGCKERHFVTISSPLA |
||
+ | TQIPQAVGAAYAAKRANANRVVICYFGEGAASEGDAHAGFNFAATLECPIIFFCRNNGYAISTPTSEQYR |
||
+ | GDGIAARGPGYGIMSIRVDGNDVFAVYNATKEARRRAVAENQPFLIEAMTYRIGHHSTSDDSSAYRSVDE |
||
+ | VNYWDKQDHPISRLRHYLLSQGWWDEEQEKAWRKQSRRKVMEAFEQAERKPKPNPNLLFSDVYQEMPAQL |
||
+ | RKQQESLARHLQTYGEHYPLDHFDK</nowiki> |
||
+ | |||
+ | ==Neutral mutations== |
||
+ | |||
+ | ==Disease causing mutations== |
||
+ | Several disease causing mutations are reported in [http://www.omim.org/entry/608348 OMIM]. Following table summarize the reported allelic variations: |
||
+ | |||
+ | {| class="wikitable" border="1" style="width:500px" |
||
+ | |+ Reported allelic variants in OMIM |
||
+ | |- |
||
+ | ! ID |
||
+ | ! Variant type |
||
+ | ! Mutation detail |
||
+ | ! Cause |
||
+ | ! Severity |
||
+ | |- |
||
+ | | 1 || substitution || TYR393ASN || [[Maple Syrup Urine Disease|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== |
||
+ | [http://www.ncbi.nlm.nih.gov/gene/593 branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA)] |
||
+ | |||
+ | [http://www.ncbi.nlm.nih.gov/nuccore/260593636?report=graph RefSeqGene of branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA)] |
||
+ | |||
+ | [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] |
||
+ | |||
+ | [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] |
||
+ | |||
+ | [http://www.ncbi.nlm.nih.gov/protein/NP_000700.1 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial isoform 1 precursor (Homo sapiens)] |
||
+ | |||
+ | [http://www.omim.org/ Online Mendelian Inheritance in Man] |
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)