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Yersinia enterocolitica

Table of Contents
  1. General Information
    1. NCBI Taxonomy ID
    2. Disease
    3. Introduction
  2. Vaccine Related Pathogen Genes
    1. LcrV (Protective antigen)
    2. aroA (Virmugen)
    3. htrA (Virmugen)
    4. ompR (Virmugen)
    5. sodA (Virmugen)
  3. Vaccine Related Host Genes
    1. Ifng (Interferon gamma)
    2. IgG
  4. Vaccine Information
    1. Y. enterocolititica Subunit V Antigen Protein Vaccine
    2. Yersinia enterocolitica aroA mutant vaccine
    3. Yersinia enterocolitica htrA mutant vaccine
    4. Yersinia enterocolitica ompR mutant vaccine
    5. Yersinia enterocolitica sodA mutant vaccine
  5. References
I. General Information
1. NCBI Taxonomy ID:
393305
2. Disease:
Yersiniosis
3. Introduction
Yersinia enterocolitica is a species of gram-negative coccobacillus-shaped bacterium, belonging to the family Enterobacteriaceae. Primarily a zoonotic disease (cattle, deer, pigs, and birds), animals that recover frequently become asymptomatic carriers of the disease. Acute Y. enterocolitica infections produce severe diarrhea in humans, along with Peyer's patch necrosis, chronic lymphadenopathy, and hepatic or splenic abscesses. Additional symptoms may include entero-colitis, fever, mesenteric adenitis, erythema nodosum and acute terminal ileitis, which may be confused with appendicitis or Crohn's disease. Because Yersinia is a siderophilic (iron-loving) bacteria, people with hereditary hemochromatosis (a disease resulting in high body iron levels) are more susceptible to infection with Yersinia (and other siderophilic bacteria). In fact, the most common contaminant of stored blood is Y. enterocolitica.

Treatment of Y. enterocolitica infections often requires aggressive antibiotic therapy, typically involving ciprofloxacin, chloramphenicol, ampicillin, and polymyxin. However, some gastoenterologists, especially in Scandinavia, would say that antibiotic treatment should be initiated only when the patient has significant and persisting symptoms of gastroenteritis (Wiki: Yersinia enterocolitica).
1. aroA
  • Gene Name : aroA
  • Sequence Strain (Species/Organism) : Yersinia enterocolitica subsp. enterocolitica 8081
  • NCBI Gene ID : 4713234
  • NCBI Protein GI : 123441850
  • Locus Tag : YE1538
  • Genbank Accession : AM286415
  • Protein Accession : YP_001005833
  • Taxonomy ID : 393305
  • Gene Starting Position : 1726120
  • Gene Ending Position : 1727406
  • Gene Strand (Orientation) : +
  • Protein Name : 3-phosphoshikimate 1-carboxyvinyltransferase
  • Protein pI : 5.16
  • Protein Weight : 43855.83
  • Protein Length : 428
  • Protein Note : catalyzes the formation of 5-O-(1-carboxyvinyl)-3-phosphoshikimate from phosphoenolpyruvate and 3-phosphoshikimate in tryptophan biosynthesis
  • DNA Sequence : Show Sequence
    >gi|123440403:1726120-1727406 Yersinia enterocolitica subsp. enterocolitica 8081, complete genome
    CATGCTGGAATCCCTGACTTTACACCCCATTGCCCTGATTAATGGCACTGTTAATTTACCCGGTTCTAAA
    AGTGTTTCTAACCGTGCACTTCTTCTGGCAGCGCTGGCCGAGGGGACAACTCAGCTGAATAACTTGTTAG
    ACAGTGATGACATTCGCCATATGCTTAATGCTCTACAGGCATTGGGGGTGAAATATCGCCTGTCTGCTGA
    TCGTACCCGCTGTGAGGTTGATGGATTGGGCGGCAAATTGGTTGCTGAACAGCCATTAGAATTGTTTTTG
    GGTAATGCCGGCACGGCCATGCGCCCATTGGCTGCGGCACTGTGCCTGGGGAAAAATGACATTGTATTGA
    CCGGCGAACCACGCATGAAAGAGCGGCCAATTGGTCATTTGGTTGATGCATTGCGTCAGGGCGGAGCACA
    GATTGATTATCTGGAGCAAGAAAACTACCCGCCGTTGCGCATACGCGGGGGCTTTCGTGGCGGTAAACTC
    ACCGTAGACGGCAGTGTTTCCAGTCAATTCCTCACGGCACTTTTGATGACCGCTCCCTTAGCTGAACAAG
    ATACTGAAATTCAGATCCAAGGGGAGTTGGTGTCTAAGCCTTATATCGACATTACGTTGCATCTGATGAA
    AGCCTTCGGTGTGGATGTCGTTCATGAAAATTATCAGATTTTTCATATTAAAGGCGGGCAGACTTACCGC
    TCACCAGGTATCTATCTGGTTGAAGGTGATGCGTCTTCTGCATCTTATTTCCTCGCCGCAGCTGCTATCA
    AAGGTGGAACAGTCCGCGTAACCGGCATTGGTAAACAAAGTGTACAAGGTGATACCAAGTTTGCTGATGT
    ACTGGAGAAAATGGGCGCTAAAATCAGTTGGGGTGATGATTATATCGAGTGCAGCCGTGGTGAATTACAG
    GGTATCGATATGGATATGAACCATATTCCTGATGCTGCAATGACCATTGCTACCACCGCACTGTTTGCCG
    ACGGCCCGACTGTTATTCGTAATATCTATAACTGGCGAGTGAAGGAAACCGACCGCTTATCCGCGATGGC
    GACTGAATTGAGAAAAGTGGGCGCGGAAGTGGAAGAGGGGCAAGACTACATTCGGGTGGTGCCCCCTGCG
    CAGCTAATCGCAGCCGAAATAGGGACTTATAATGACCACCGCATGGCGATGTGTTTCTCGCTGGTGGCTT
    TATCTGACACGCCGGTGACTATCCTTGATCCGAAATGTACCGCGAAAACATTCCCTGACTACTTTGAACA
    ACTGGCCCGATTGAGCCAGATAGCCTA
  • Protein Sequence : Show Sequence
    >gi|123441850|ref|YP_001005833.1| 3-phosphoshikimate 1-carboxyvinyltransferase [Yersinia enterocolitica subsp. enterocolitica 8081]
    MLESLTLHPIALINGTVNLPGSKSVSNRALLLAALAEGTTQLNNLLDSDDIRHMLNALQALGVKYRLSAD
    RTRCEVDGLGGKLVAEQPLELFLGNAGTAMRPLAAALCLGKNDIVLTGEPRMKERPIGHLVDALRQGGAQ
    IDYLEQENYPPLRIRGGFRGGKLTVDGSVSSQFLTALLMTAPLAEQDTEIQIQGELVSKPYIDITLHLMK
    AFGVDVVHENYQIFHIKGGQTYRSPGIYLVEGDASSASYFLAAAAIKGGTVRVTGIGKQSVQGDTKFADV
    LEKMGAKISWGDDYIECSRGELQGIDMDMNHIPDAAMTIATTALFADGPTVIRNIYNWRVKETDRLSAMA
    TELRKVGAEVEEGQDYIRVVPPAQLIAAEIGTYNDHRMAMCFSLVALSDTPVTILDPKCTAKTFPDYFEQ
    LARLSQIA
  • Molecule Role : Virmugen
  • Molecule Role Annotation : An aroA mutant is highly attenuated in mice, and after 3 doses induces significant protection from challenge with wild type Y. enterocolitica (Bowe et al., 1989).
  • Related Vaccine(s): Yersinia enterocolitica aroA mutant vaccine
2. htrA
  • Gene Name : htrA
  • Sequence Strain (Species/Organism) : Yersinia enterocolitica subsp. enterocolitica 8081
  • NCBI Gene ID : 4715899
  • NCBI Protein GI : 123441096
  • Locus Tag : YE0741
  • Genbank Accession : AM286415
  • Protein Accession : YP_001005085
  • Taxonomy ID : 393305
  • Gene Starting Position : 861810
  • Gene Ending Position : 863246
  • Gene Strand (Orientation) : +
  • Protein Name : serine endoprotease
  • Protein pI : 8.59
  • Protein Weight : 45391.81
  • Protein Length : 478
  • Protein Note : Also known as gsrA; htrA; ptdprotease Do; required at high temperature; degrades damaged proteins
  • DNA Sequence : Show Sequence
    >gi|123440403:861810-863246 Yersinia enterocolitica subsp. enterocolitica 8081, complete genome
    CATGAAAAAAACAACTTTAGTGTTAAGTGCATTGGCATTGAGCATCGGTTTAGCCATGGGGCCGGTTTCT
    TCTGTCGTTGCGGCAGAAACGGCCTCTTCCAGCAGCCAGCAGCTCCCTAGCCTGGCGCCAATGCTAGAGA
    AGGTAATGCCTTCGGTTGTGAGTATCAATGTGGAGGGAAGTGCTCAGGTAAGTAATGCCGGTGGCATACC
    ACCACAGTTCCAGCAATTCTTTGGTGATGATTCGCCATTCTGCCAGGACGGTTCTCCGTTCCAAGGGTCA
    CCAATGTGTCAGGGGGGGCCTGGTAGCAGGGGGGGAGCACCCAGCAAGCAGGATTTCCGTGCGCTGGGTT
    CTGGCGTAATTATTGATGCTGCTAAAGGTTATGTCGTCACTAATAACCACGTAGTAGATAATGCAACCAA
    AATCAATGTTAAGCTCAGTGATGGCCGTAGTTATGAAGCAAAAGTGATTGGTAAAGATCCGCGTACTGAT
    ATTGCATTATTGCAGCTGAAAGACGCTAAAAATCTGACTGCGATTAAAATTGCCGACTCCGATCAACTGC
    GCGTTGGGGATTATACCGTAGCTATCGGTAACCCATACGGCCTGGGTGAAACCGTCACTTCCGGTATCGT
    GTCGGCGTTGGGCCGCAGTGGTTTGAATGTGGAAAACTACGAAAACTTTATCCAGACTGACGCGGCAATT
    AACCGTGGTAACTCCGGTGGTGCATTGATCAATCTGAACGGTGAACTGATCGGGATCAACACGGCTATTC
    TGGCACCTGATGGCGGCAACATCGGTATCGGTTTTGCTATCCCAAGTAACATGGTGAAAAACCTGACCTC
    ACAGATGGTTGAATTTGGTCAGGTGAAACGCGGTGAACTGGGCATTATGGGTACAGAGCTGAACTCTGAG
    CTGGCGAAAGCCATGAAGGTTGATGCGCAGAAAGGGGCCTTTATCAGTCAGGTACTGCCAAAATCTGCTG
    CAGCTAAAGCAGGGATTAAAGCGGGTGATGTGATTGTCAGCATGAATGGCAAAGCCATCAATAGCTTCGC
    TGGCTTCCGTGCCGAGATTGGTACTTTGCCTGTGGGCAGCAAAATGACCTTGGGTCTGTTGCGCGACGGT
    AAGCCTGTCAACGTGGAAGTGACATTAGAGCAAAGCAGCCAAACTCAAGTTGATTCAGGCAATCTCTACA
    CTGGTATTGAAGGGGCTGAGCTGAGCAACTCTGATGTGAATGGTAAGAAAGGTGTGAAAGTTGATAGTGT
    GAAACCTGGCACTGCTGCTGCGCGTATAGGCCTGAAAAAAGGCGATGTCATCATGGGTGTCAACCAGCAA
    CCCGTTCAGAATCTGGGTGAGCTGCGGAAAATCCTTGATACCAAACCATCGGTATTGGCATTGAGCATTC
    AGCGTGGTGATACTTCACTCTATCTGCTGATGCAGTA
  • Protein Sequence : Show Sequence
    >gi|123441096|ref|YP_001005085.1| serine endoprotease [Yersinia enterocolitica subsp. enterocolitica 8081]
    MKKTTLVLSALALSIGLAMGPVSSVVAAETASSSSQQLPSLAPMLEKVMPSVVSINVEGSAQVSNAGGIP
    PQFQQFFGDDSPFCQDGSPFQGSPMCQGGPGSRGGAPSKQDFRALGSGVIIDAAKGYVVTNNHVVDNATK
    INVKLSDGRSYEAKVIGKDPRTDIALLQLKDAKNLTAIKIADSDQLRVGDYTVAIGNPYGLGETVTSGIV
    SALGRSGLNVENYENFIQTDAAINRGNSGGALINLNGELIGINTAILAPDGGNIGIGFAIPSNMVKNLTS
    QMVEFGQVKRGELGIMGTELNSELAKAMKVDAQKGAFISQVLPKSAAAKAGIKAGDVIVSMNGKAINSFA
    GFRAEIGTLPVGSKMTLGLLRDGKPVNVEVTLEQSSQTQVDSGNLYTGIEGAELSNSDVNGKKGVKVDSV
    KPGTAAARIGLKKGDVIMGVNQQPVQNLGELRKILDTKPSVLALSIQRGDTSLYLLMQ
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A htrA mutant in Yersinia enterocolitica was attenuated and provided partial protection against challenge in mice (Li et al., 1996),
  • Related Vaccine(s): Yersinia enterocolitica htrA mutant vaccine
3. LcrV
  • Gene Name : LcrV
  • Sequence Strain (Species/Organism) : Yersinia enterocolitica
  • VO ID : VO_0011321
  • NCBI Gene ID : 1449458
  • NCBI Protein GI : 32470278
  • Locus Tag : pYVe8081_p09
  • Genbank Accession : AF336309
  • Protein Accession : NP_863514
  • Taxonomy ID : 630
  • Plasmid No : pYVe8081
  • Gene Starting Position : 12283
  • Gene Ending Position : 13257
  • Gene Strand (Orientation) : -
  • Protein Name : LcrV
  • Protein pI : 5.5
  • Protein Weight : 35777.8
  • Protein Length : 324
  • DNA Sequence : Show Sequence
    >gi|32470270:12283-13257 Yersinia enterocolitica 8081 plasmid pYVe8081, complete sequence
    ATTACCTCGTGTCATCTAGCAGACGTTGCATTACTGAATCATATTTCTGAATGAAACGGTTCAGTGCTTC
    AATAGCTGAATTAAAACGTGATGTAATATCAGACAGCTGAGTTGTTTTTTGGCTAACCAAGTCGTTGAGC
    GGCCTGGACTTATCCGAGCAGGCGGTGGCAAAGTGAGATAATTCATTATTATCTTTATTATAAGAGTATG
    AATTTTTCAGGTTACCCAACGCCCCGGTTCTTTTATTCTCACTTTCAAGAAAGTTCTTTATCGAGACTAT
    TTTTTTTTCGGTCTCACCTTCCTTAATGGTGGTTTGAGACATTTTCTCAAGAATTTTGTACTCTGCGCTG
    GCTTTAAAAATCTCTTCATCTGTATAACCATATAAATTTTTATCCATGAGATTAATTGATTTATCATGGA
    TATTTATGGTGCCACTATTCGACAGATACTTATTAATTTCAGCTTGAATAACTGAATAAATTTTTAATTC
    GGCGGTAAGCTCAGCTAATTCTTCACGCAACTTGCTACGGGCATCACCATGATGATTCATTGAATCAACA
    ATCACTTTCAAAATATCATCATCGATACGATCGGCGGTTAAAGAGAAATGCATTACTGCCATGAACGCTC
    GCAACTCCCATTGTGTATTCGGCGATGATTCAAGGAACTCTTTTACTCGCTTGATGCCATTTTGCAGTTG
    GTTGTCATAATGACCGCCTTTAAGAATGGCATCCTCGGGTAGAAAATAAGCCAGGATTTTCTTGAGTAAT
    TCGATATCATCAGTAATTACCCTTTCGGCAAAAACCTCCGAATCTTTTTTGGGATCATATTTAATGGAAA
    TATCTATCTTTTTATCTTTGACTAACTGAACCAATTCTTCTAAAACTGAAGAACCATGACCAGTAAGTTG
    TTCCACCCTAACTTTTTCTAGATCCTCAATAAAATGTTGTGGGTTTTGTTCGTAGGCTCTAATCA
  • Protein Sequence : Show Sequence
    >gi|32470278|ref|NP_863514.1| LcrV [Yersinia enterocolitica]
    MIRAYEQNPQHFIEDLEKVRVEQLTGHGSSVLEELVQLVKDKKIDISIKYDPKKDSEVFAERVITDDIEL
    LKKILAYFLPEDAILKGGHYDNQLQNGIKRVKEFLESSPNTQWELRAFMAVMHFSLTADRIDDDILKVIV
    DSMNHHGDARSKLREELAELTAELKIYSVIQAEINKYLSNSGTINIHDKSINLMDKNLYGYTDEEIFKAS
    AEYKILEKMSQTTIKEGETEKKIVSIKNFLESENKRTGALGNLKNSYSYNKDNNELSHFATACSDKSRPL
    NDLVSQKTTQLSDITSRFNSAIEALNRFIQKYDSVMQRLLDDTR
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : Mice actively immunized using a recombinant V antigen (rVagHis, encoded by lcrV gene) of Y. enterocolitica were completely protected against challenge with both, Y. enterocolitica 0:8 and Y. pseudotuberculosis serotype III (Schmidt et al., 1999).
  • Related Vaccine(s): Y. enterocolititica Subunit V Antigen Protein Vaccine
4. ompR
  • Gene Name : ompR
  • Sequence Strain (Species/Organism) : Yersinia enterocolitica subsp. enterocolitica 8081
  • NCBI Gene ID : 4716266
  • NCBI Protein GI : 123444180
  • Locus Tag : YE4004
  • Genbank Accession : AM286415
  • Protein Accession : YP_001008150
  • Taxonomy ID : 393305
  • Gene Starting Position : 4355750
  • Gene Ending Position : 4356469
  • Gene Strand (Orientation) : +
  • Protein Name : osmolarity response regulator
  • Protein pI : 6.54
  • Protein Weight : 25640.73
  • Protein Length : 239
  • Protein Note : Also known as ompB; ompRpart of two-component system EnvZ/OmpR; regulates transcription of outer membrane porin genes ompC/F; under high osmolarity EnvZ functions as kinase/phosphotransferase and phosphorylates OmpR; the result is increased expression of ompC and repression of ompF; also functions in regulation of other genes; forms dimers upon phosphorylation
  • DNA Sequence : Show Sequence
    >gi|123440403:4355750-4356469 Yersinia enterocolitica subsp. enterocolitica 8081, complete genome
    AATGCAAGAGAATCACAAGATTCTGGTCGTTGATGACGATATGCGCCTACGCGCGCTATTGGAACGTTAC
    CTGACAGAGCAAGGTTTCCAGGTGCGCAGTGTTGCCAATGCTGAACAGATGGATCGCTTGCTAACTCGTG
    AGTCCTTCCACCTGATGGTGCTCGACCTGATGTTACCGGGGGAAGATGGCCTGTCTATCTGCCGCCGTCT
    GCGCAGTCAAAGTAACCCAATGCCTATCATTATGGTGACGGCAAAGGGTGAAGAAGTTGACCGTATCGTC
    GGGCTGGAAATTGGTGCCGATGACTATATTCCAAAGCCATTTAACCCACGCGAACTGCTGGCTCGTATCC
    GCGCGGTGCTACGCCGTCAGGCCAACGAACTTCCAGGTGCCCCTTCACAAGAAGAAGCGGTGATTGCATT
    TGGTAAGTTCAAACTGAACTTGGGTACCCGCGAGATGTTCCGTGAAGATGAACCTATGCCACTGACCAGC
    GGCGAGTTTGCAGTGCTGAAAGCTTTAGTCAGCCATCCGCGTGAGCCATTGTCTCGCGATAAACTGATGA
    ATTTGGCTCGTGGCCGTGAATACAGTGCAATGGAACGCTCTATCGACGTACAGATTTCACGTTTGCGCCG
    CATGGTAGAAGAAGACCCAGCTCATCCACGCTATATCCAAACCGTATGGGGCTTGGGCTACGTATTTGTG
    CCGGACGGCAGTAAAGCATG
  • Protein Sequence : Show Sequence
    >gi|123444180|ref|YP_001008150.1| osmolarity response regulator [Yersinia enterocolitica subsp. enterocolitica 8081]
    MQENHKILVVDDDMRLRALLERYLTEQGFQVRSVANAEQMDRLLTRESFHLMVLDLMLPGEDGLSICRRL
    RSQSNPMPIIMVTAKGEEVDRIVGLEIGADDYIPKPFNPRELLARIRAVLRRQANELPGAPSQEEAVIAF
    GKFKLNLGTREMFREDEPMPLTSGEFAVLKALVSHPREPLSRDKLMNLARGREYSAMERSIDVQISRLRR
    MVEEDPAHPRYIQTVWGLGYVFVPDGSKA
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A ompR mutant in Yersinia enterocolitica was attenuated and provided a partial protection from challenge in mice (Dorrell et al., 1998).
  • Related Vaccine(s): Yersinia enterocolitica ompR mutant vaccine
5. sodA
  • Gene Name : sodA
  • Sequence Strain (Species/Organism) : Yersinia enterocolitica subsp. enterocolitica 8081
  • NCBI Gene ID : 4716532
  • NCBI Protein GI : 123444307
  • Locus Tag : YE4138
  • Genbank Accession : AM286415
  • Protein Accession : YP_001008274
  • Taxonomy ID : 393305
  • Gene Starting Position : 4530099
  • Gene Ending Position : 4530722
  • Gene Strand (Orientation) : +
  • Protein Name : superoxide dismutase
  • Protein pI : 6.73
  • Protein Weight : 22109.22
  • Protein Length : 207
  • Protein Note : SodA; manganese binding; only present under aerobic conditions; destroys free radicals
  • DNA Sequence : Show Sequence
    >gi|123440403:4530099-4530722 Yersinia enterocolitica subsp. enterocolitica 8081, complete genome
    TATGAGTTACTCACTGCCATCCCTGCCTTATGCTTATGACGCCCTGGAACCACACTTCGATAAGCAGACG
    ATGGAAATCCATCACACCAAACACCACCAAACCTATGTTAACAATGCAAACACGGTGTTGGAGAGCTTCC
    CTGAACTGGCTAAATTCAGTGTTGAAGATCTGATCAAAGATCTGGACAAAGTTCCAGCTGAAAAACGCAC
    CTTTATGCGTAATAACGCCGGCGGTCACGCTAACCACAGCCTGTTCTGGAAGGGCTTGAAACTGGGCACC
    ACTCTGACCGGTGACCTGAAAGCCGCTATCGAGCGCGACTTCGGCAGCATTGACAGCTTCAAAGAAAAAT
    TTGAACAAGCTGCGGCAACGCGTTTCGGTTCAGGCTGGGCCTGGCTGGTACTGAAAGACGACGGCAAACT
    GGCTGTTGTTTCGACTGCTAACCAAGACAGCCCGCTGATGGGTGAAGCTGTTTCTGGCGCATCAGGTTTC
    CCAATTGTGGGCCTGGATGTGTGGGAACACGCTTACTATCTGAAATTCCAAAACCGCCGCCCAGACTACA
    TCAAAGCATTCTGGAACGTGGTTAACTGGGACGAAGCAGCCGCGCGCTTCGCTCAAGCTAAGTA
  • Protein Sequence : Show Sequence
    >gi|123444307|ref|YP_001008274.1| superoxide dismutase [Yersinia enterocolitica subsp. enterocolitica 8081]
    MSYSLPSLPYAYDALEPHFDKQTMEIHHTKHHQTYVNNANTVLESFPELAKFSVEDLIKDLDKVPAEKRT
    FMRNNAGGHANHSLFWKGLKLGTTLTGDLKAAIERDFGSIDSFKEKFEQAAATRFGSGWAWLVLKDDGKL
    AVVSTANQDSPLMGEAVSGASGFPIVGLDVWEHAYYLKFQNRRPDYIKAFWNVVNWDEAAARFAQAK
  • Molecule Role : Virmugen
  • Molecule Role Annotation : A sodA mutant in Yersinia enterocolitica was highly attenuated and mice immunized with a single oral dose of the mutant strain were protected against a lethal oral-challenge infection with wild-type Y. enterocolitica (Igwe et al., 1999).
  • Related Vaccine(s): Yersinia enterocolitica sodA mutant vaccine
1. Ifng (Interferon gamma)
  • Gene Name : Ifng (Interferon gamma)
  • Sequence Strain (Species/Organism) : Mouse
  • NCBI Gene ID : 15978
  • NCBI Protein GI : 33468859
  • Genbank Accession : NM_008337
  • Protein Accession : NP_032363.1
  • Other Database IDs : MGI:107656; UniProt: P01580
  • Taxonomy ID : 10090
  • Gene Strand (Orientation) : ?
  • DNA Sequence : Show Sequence
    >gi|145966741|ref|NM_008337.3| Mus musculus interferon gamma (Ifng), mRNA
    ATAGCTGCCATCGGCTGACCTAGAGAAGACACATCAGCTGATCCTTTGGACCCTCTGACTTGAGACAGAA
    GTTCTGGGCTTCTCCTCCTGCGGCCTAGCTCTGAGACAATGAACGCTACACACTGCATCTTGGCTTTGCA
    GCTCTTCCTCATGGCTGTTTCTGGCTGTTACTGCCACGGCACAGTCATTGAAAGCCTAGAAAGTCTGAAT
    AACTATTTTAACTCAAGTGGCATAGATGTGGAAGAAAAGAGTCTCTTCTTGGATATCTGGAGGAACTGGC
    AAAAGGATGGTGACATGAAAATCCTGCAGAGCCAGATTATCTCTTTCTACCTCAGACTCTTTGAAGTCTT
    GAAAGACAATCAGGCCATCAGCAACAACATAAGCGTCATTGAATCACACCTGATTACTACCTTCTTCAGC
    AACAGCAAGGCGAAAAAGGATGCATTCATGAGTATTGCCAAGTTTGAGGTCAACAACCCACAGGTCCAGC
    GCCAAGCATTCAATGAGCTCATCCGAGTGGTCCACCAGCTGTTGCCGGAATCCAGCCTCAGGAAGCGGAA
    AAGGAGTCGCTGCTGATTCGGGGTGGGGAAGAGATTGTCCCAATAAGAATAATTCTGCCAGCACTATTTG
    AATTTTTAAATCTAAACCTATTTATTAATATTTAAAACTATTTATATGGAGAATCTATTTTAGATGCATC
    AACCAAAGAAGTATTTATAGTAACAACTTATATGTGATAAGAGTGAATTCCTATTAATATATGTGTTATT
    TATAATTTCTGTCTCCTCAACTATTTCTCTTTGACCAATTAATTATTCTTTCTGACTAATTAGCCAAGAC
    TGTGATTGCGGGGTTGTATCTGGGGGTGGGGGACAGCCAAGCGGCTGACTGAACTCAGATTGTAGCTTGT
    ACCTTTACTTCACTGACCAATAAGAAACATTCAGAGCTGCAGTGACCCCGGGAGGTGCTGCTGATGGGAG
    GAGATGTCTACACTCCGGGCCAGCGCTTTAACAGCAGGCCAGACAGCACTCGAATGTGTCAGGTAGTAAC
    AGGCTGTCCCTGAAAGAAAGCAGTGTCTCAAGAGACTTGACACCTGGTGCTTCCCTATACAGCTGAAAAC
    TGTGACTACACCCGAATGACAAATAACTCGCTCATTTATAGTTTATCACTGTCTAATTGCATATGAATAA
    AGTATACCTTTGCAACC
  • Protein Sequence : Show Sequence
    >gi|33468859|ref|NP_032363.1| interferon gamma [Mus musculus]
    MNATHCILALQLFLMAVSGCYCHGTVIESLESLNNYFNSSGIDVEEKSLFLDIWRNWQKDGDMKILQSQI
    ISFYLRLFEVLKDNQAISNNISVIESHLITTFFSNSKAKKDAFMSIAKFEVNNPQVQRQAFNELIRVVHQ
    LLPESSLRKRKRSRC
  • Molecule Role Annotation : IFN-gamma plays a critical role in Th1 type immune response. It is important for protection against infections by various viruses and intracellular bacteria.
  • Additional Molecule Role : Vaximmutor
  • Additional Molecule Role Annotation : The experimental data demonstrated that three time vaccinations with BCG in BALB/c mice induced strong TB Ag-specific IFN-gamma immune responses in splenocytes (Wang et al., 2009).
  • Related Vaccine(s): Yersinia enterocolitica sodA mutant vaccine
2. IgG
  • Gene Name : IgG
  • Sequence Strain (Species/Organism) : Mus musculus
  • NCBI Gene ID : 16059
  • Genbank Accession : AF010213
  • Taxonomy ID : 10090
  • Chromosome No : 12
  • Gene Starting Position : 881411
  • Gene Ending Position : 914690
  • Gene Strand (Orientation) : +
  • Protein Name : immunoglobulin heavy chain (V7183 family)
  • Protein Note : Also known as IgG; IgH; VI24H; VH7183; B9-scFv; IgVH1(VSG)
  • DNA Sequence : Show Sequence
    >gi|94393741:881411-914690 Mus musculus strain 129/SvJ chromosome 12 unlocalized genomic contig, MGSCv37 alternate locus group 129/SvJ
    CATGGACTTTGGGCTCAGCTGTGTTTTCCTTGTCCTCATTTTAAGAGGTAATTTGTAGAAATAAGATCCT
    GCCAGTATTGTGTACAGGAGAAATAGAAAAATTTTTCTTTCCTCTATTTTGTTTTGTTTTGTTAGTGACA
    GTTTACAAATAAGCATTCTCTGTTGTGAGGTGCCCAGTGTGAGGTGAAGATGGTGGAGTCTGTGGGAGGC
    TTAGTGCAGCCTGTAGGGTCATTGAAACCCTCCTGTGCAGCCTCTGGATTCATTCTCACTGACTACTGAA
    TGACCTGGATCCTTCAGGCTTCAAAGAAAAGGATGGAGAGGGTGACAATAAAATTTTTCCCACTCACACC
    CACTTGCTGGCCCTGGCGTTCCCCTGTAATGAGGCACATAAAGTTTGCAAAACCAAGGGGCCTCTCTTCT
    CAATGATGGCTGACTAGGACATCTTCTGATACATATGCAGCTAGAGACATGAGCTCCCGGGATACTGGTT
    ACTTCATATTGTTGTTCCCCCACAACAGTTGCAGACCCTTTTATTTCTGTGGGTACTTTCACTAGCTCCT
    CCATTGGGGGCCCTGTGTTCCATCCAATAGCTGACTGTGAGCATCCACTTCTGTAGTTGCTAGGCCCCGG
    CATAGCCTCACAAGAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTTGCTGGTGTATGCAATGGTGTC
    AGAGTTTGGAGTCTGATTATGGGATGGATCCCCAGGTATGGCAAACTCTAGATGGTCCATCCTTTCCCAA
    CAATAATTTTTAATGGTGGAGATAGCACCTACTATCCAGACACAATGAAGGGCCAATTCACTATCTCTAG
    AGATGATGCCAAAAACACACTTTACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTATACA
    TATATTCCTAAGCTTGAGTAAGTGGACTTAAACTGATTCCATCACAACTTGCATGAGATGGATATTCCCC
    AGTGTTAAGACCTGTCACCATCACTGTCAATCAGAAGACAAAGTTTATGCACAACAAAACAAAAAAACCA
    AAAGCAGAGGCCTCCAATTACAAGTAATAGACCCAGACCCACAGTCTCTGAAAACTGACTGTACAGTTGG
    ATCCAGTCTTTTACTTCTTTTCCCTGGATTTTATATTACTGAGGAAATGAGGAAAGCTCTACAATATCTG
    TTCTCCATAGTGCTCAACACCTCCAAGCACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTTCTT
    GTCTTGTAGACTACTTCAACCTATTTTGTACTCCAGTTAATGAAACTCAAGTCTAGCAGCCTGTCACTGT
    TTATTCTAAAGTATTATGAACAGGTGACCTCCCATCCTTCCCCAACGCAATAATCATATTTAGGAATTTG
    AGGTTTTATGAGATATGATCTCAGGGTAGAGAGAGAAAGCAAACTACATAGAAATATAGACTGACATAAA
    TCAAGACTTGCATAAGCTAGTCCCCAAGTTCCATGTCCCTAAGTGGCAAGGACTATCTTCTGAGCCTAAT
    GAGATGAGATCCAAATCAAACCTCCTGGGTCTTTTTAGATAAACATGTGAGATCAATAGACTAAATGCTT
    TGGCTGGGCTTCCTTGCAATCCAATTCCCAAACAAAAATGGATCTGGCTCCACAGACACCACAAGAATAG
    TCTTAAATAGTTCTTTAAGTAGAATGTCTGATCACTACGAGCCCAATTCCATCCTAAATACTCTTCTGGA
    TTATACATAAATAAAAATTGAACATAGGGCATGGGGCACTGATCTCCCTGTGCTACATGAATGGGGGCTC
    ATTTACTAAATGTTCCCATTTTTCTTTCTAGCGCTGCACAGTGCAAATCCTACAACTTCCTGTTTATCTA
    CAATGTGAACTCCAAACAGTACAAGAAAAAACGTTCCTTATGTTCCTCTCCAGGTTCTCCAACAAGCACA
    GAGCAACCTTCTGTCACCAGGACGGAAAACTGGAAACCTTGCTCACTGCTTCCTTTTATTCCCTCGGGAA
    CCTCCCCCAATGCAAAGCAGCCCTCAGGCAGAGGATAAAAGCTCACACAAAGACGAGAAGCCCCATCCTC
    TTCTCATAGAGCATCCATCAGAGCATGGCTGTCCTGGGGCTGCTTCTCTGCCTGGTGACTTTCCCAAGCT
    GTAAGTGTTTCAGGGTTTCAGAAGAGGGACTAAGACATGTCAGCTAGAAGATGTGTGACTAATGGTGATG
    TTGCTTGTCCCCAGGTGTCCTGTCCCAGGTGCAGCTGAAGGAGTCAGGACCTGGCCTGGTGGCGCCCTCA
    CAGAGCCTGTCCATCACATGCACCGTCTCAGGGTTCTCATTAACTAGCTATGGTGTACACTGGGTTCGCC
    AGCCTCCAGGAAAGGGTCTGGAGTGGCTGGTAGTGATATGGAGTGATGGAAGCACAACCTATAATTCAGC
    TCTCAAATCCAGACTGAGCATCAGCAAGGACAACTCCAAGAGCCAAGTTTTCTTAAAAATGAACAGTCTC
    CAAACTGATGACACAGCCATGTACTACTGTGCCAGAAACACAGTGTGGGAAGTCCAATGTGAGCCTGCAC
    AAATACTTCTCTGCAGGGATGATCACAACCAGCAGGGGGCGCTGATGACCCAAAGGGACTTCCCAGGATC
    TCTTCTGGAATCTAGGGAGTTCTGGCCTGTGTCTATCAGCATGTGTTTCAATGTTAGAGTTGTGAGTTTT
    CCTTCCAGCAACAGAGATATTTTAGAGCCCACTTTTCATGGTCATTCTACTAAATTTGTTCACATAGTGG
    AAAGATTTGTTAAATGATTCTATAGTCTAATAGGGTCAAACAAAAACAAATAATTGAGTTCATATCTACC
    AAAAAAAAAAAAATTCCCTCAAAGTGGACAACTGTGTAGGTGAGGAAAACCAGGGGGATTTGGGAATAGA
    TTATTTCTCTCCCGACTGTGGTGTTAGTCACCTTTCAGCCATTTACTGTATTTAATTCATGTTTAAAGTT
    AATTGTATTCATCTTCCCTAACATGAAGTTTTCAAACACATGTCCACAATTTAATGATGACACAGTTATC
    ATTGTGAATGATAACTCATAAGATCTCTCTCCATATATGAAACACACGATATTCTGTTATTAGCTATAGC
    CAACAAAGTTACATATCATTATTATTACTGAAATAATTCTTCCCATCTAACTGAATAGTTTTCTCACTCG
    ACACTGCCTATGCTGCGATCAGCCTGCTCTAATTTTACCTTTGCTCAGAGCACTGCTTTCTGTTTCATTT
    GATAAGATGGTGCCTGGTTGTCACTGAAAATGTGTCCTCCAGTTTCACAGTGATTAATGTGATTTTCAGT
    ACATTGAGAACAGAGCCACAGCAAAAATGAGATGGAATGTCATCATTTTTACGCCAGGTGCTGCAGAAAT
    AGCTAGGTGGTTAAGAGAGAATATTGAACTTTGAGGGGTTCAGATTAAATTCCTGATACCCACAATGTGC
    ACCTCATAACCACATGTACATATAGAAAACTCAGTATAAATGTGGCCTCCGTGAGCACCACACTACTCCC
    ACAAACACATATACACATAATTAAAAGTAAAGATTTTAGAAAAATGGCTAATCTAATGATAGGAAGTAGT
    CAAAAAGAGAGTTCTTTTGTCATGTACATATGTGTAGCAGACTTAAATGTTAAACATTCAAGAATACATT
    CCTCGATCCACATTAAAATTTTGCAAAGAGTAGCACAGACGGTGGCAATTGCTAAACTTATATCTAGAAA
    CACAATTATGTGTGGTGATATTTAATTACACATTTATACCAGGACATATGACAATATGGAAACCAAACAT
    GTTGTATCCACATGCTCTAAGGAAAACTAAATGGAGTGTGATAAAACCAAAGAAAATGTGAATATGAAAT
    ATTTTTCCAACTCTGCATCTTAAAACGGTTTCTTTCATGTGTCATATCTGCTATGAGGACTTTCTTCTGC
    CCATGTCCAACTCCAGAGCATGCCACAGCAGGAAGACCTACAGGTATTACTTCTCTGCACCCAGGAAAAC
    CACCTCTGTCCTGACCCTGCAGCTCTCAGAAGAGCCCAGACCTTCATTCTCAGGCCCTCATCCAGTAATC
    AGCACTGAATACAGAGCACTCACCATGGACTTTGGGCTCAGCTTGGTTTTCCTTGTCCTTATTTTAAAAG
    GTAATTCATAGAGATAAGATTCTATCTGTTTTGTGTACATGAGAAACAGAAAAATTGTATTGTTTCTCTA
    TTTTGTTTTGTTTTGTTAGTGACAGTTTCTGACTCAAGATTCTCTGTTTGAAGGTACCCAGTGTGAGGTG
    AAGCTGGTGAAGTCTAAGGGGAGGCATAGTGCAGCCTAGAAGGTCCATGATACTCTACTGTGCAGCCTCG
    GATTCACTGTAAGTGACGACTGGTTTGTCCGTGTTTGCCAGGCTCCAAAGAAGGGGCTGCAGTGGGGGAT
    GGGAATAATTTTTCATGGTTGTGGTAGCCCCTCTTATGCAGACACCTTGAAGAAGTGGGTTGGACGTAAC
    ATATTCAGAATCAATATTTAAAGATTCTAATCCTTGAAGATATCACTTTTGACCAAGTATATATGAACCA
    TGTTACTGAGGTTTATGGAGGTTTGAGTATGTTAGGTCCATGGATAGGGAAAATATTAGGGGATTTTAGG
    AGTAACTGAGGCTTGTTGTAGGAAGGACATCACTGTAGGGGTAGGCTCCGTGTTCCTATCTTCAAGCTCT
    ACCCAGTGCAGAATAGAGCCCTCTTCTGCCGGCAAGTGGAAAGAGTTTCTCTTCCTGGCTGCCTTCAATC
    CAAGTTGTAGAATATCAAATCTCCTAACACTATGACTGCGAGCATGCTGACATGCGTCCCACCATAAAAA
    TAGACTGAACCTCTGAAGCTTTAAGCCAGCCTCTAGTAACTGTATTCTTTAATAAGACTGAACTTGGCTA
    TGGTGTCTTTTCACAGTAAAATGGAAACATAGACAAGGTTCTAACTCTCTGTACTAGAGGACCATCTCTA
    TGTCCTTGGTGTTGTATGTAAATTATTGAACAAATACTATAGACAAGTTGTATGGCCAAAAGTCCATCCC
    CTTCAACAATCTACTATCTGGAACCATATAGATTAGATTCCTTTCCTGCACTCATTTCCCTTACTTGCTG
    AGACATTTTGAAGACATGCTCAGAATCCCTGAACTTCCTGCTGAAAAAAAAATACCCCTCCAATTTGAAG
    ACAGTTCTCTTCCAAAATTCATCATAAATACTGATCCACATGTCCAGGCATATCATGTAGTTTTAAAAAA
    CAAACCAATCAATGCTAAAGTGGGTAAGTGCCTACATCATTGGTTTATGTCTGTTCATAACCTGGTATAT
    AGCTAGAGACCAGGACTGCATGTTTCTCCTAGGCCACACCTCTCCCACAAATGCTGGCTCTGCCTCTCCA
    GAATTCCAAGATCATGGATCTCTGGGTCCCCAAGGAACAATAAGTGTGCACTCTTGCCAGCCTGTACACT
    ACTGCACTAGCTTCTCCCCCTGGAGCTTGGTCATTGCTCAATCTTCCCTTTCCAAAGCCTGGCCAAATTC
    CTCCTACCTTTTGTTCTTTCAGTCAGGCCACCTAAGTCATCTTGAATGAAAAACAACACAAAATCTGAAC
    TTAAAATCAACAAATAATACAAGTGCTGCGCACAAAATCAATCATTCTAAACTCATCAACTATTTTATGA
    TGGAAATCTTCCAACATACAAGCTACCACCAGGTCTAAGAATTACTCATCTACATGTTGCTTCCTCTCAC
    TCACAGCCTAACCATAAAAGGGCTGTTTCTTCCTCCCATGTCCCCTCTTTTGCCTTCAGAAGCAGAAGCT
    CCACCTCCTCCTCTTTGCCCAGCAATTGGCTTCTTGTCGTCTTTATTATCATATTAATTACTTAGGGGAA
    AATCCCGTGTAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGG
    AAGGCTCACCAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAG
    CCATAGGGGCTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACG
    CCTTTCATCTGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAA
    TATAAGGACATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTG
    AGTAACTGCTAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGA
    CTCTAAGTCATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTG
    ACTAATACAGAAGTTGGTACCAGGAGTGGTTCTAGAGTAACAGAAGTACAAGGATGAATCTTTTAAAATA
    CTGGAATTGGCTTGTTGATCCACCAGCACTTTCAACTATTGAAACCTCTCCAGATTCTCTCCCTCCTGGG
    AGCTCAGAGAATTTTGAAGACCCATGGTTGAAACTATATTCCGAACTTAAAGAAGCAAATGCCCTTGATT
    TTCTTAATGAATTAGGTGATTCAGTGCACAAAGCTTTCTACAAGATGGGGAAAAAATTGGAAAATGATTT
    TACTGGCTGGCTGCTCTTAGTATCTGTGGAAAAAATGATGAATGAAAGGAAGGAGTTGTGTGATAAAATC
    GAAAGGCTCCAGACACAAGTAAACGATCTAAAAGTTGCTAAGTGTGTCCTTGAGGAGAATCTTCTCTCTT
    GTAGCAATAGAGCTCAAGTTGCAGAAAATCAAACAGAAACTCTCATTGTAAGGTTGGCTGAACTACAGCG
    AAAATTCAAGTCTCAGCCTCAGAGTGTGTCAACAGTTAAAGTAAGGGCTCTAATTGGCAAAGAATGGGAT
    CCTACAACATGGGACGGGGATGTGTGGGAAGACCATGTTGAAGCTGAGAATTTTGAATCTTCAGATTCTC
    AAGGGTTTGCCCCACCTGAGGAAGTAGTACCCTCAGCCCCACCCCTTGAAATAATGCCTTCCCCACATGA
    GGAAATTAATTTTGCAGAGTCTGATAAACCAGCAATGATTTTCACTACTGATGTTTCTCAAGGCCCACCA
    ATAGTTTCTTCTAGACCTGTAACCAGACTCAAAGCAAAACAGGCTCCTAGAGGGGAGGTAGAAAGTGTAG
    TCCATGAGGAAATTCGCTACACTACTAAGGAGCTTAATGAGTTTGCTAATTCATTCAAGCAGAAACCTGG
    TGAATATGTGTGGGAATGGATTTTAAGGGTGTGGGATAAGGGTGGAAGGAACATAAGACTAGAGCAGGCT
    GAGTTTATTGACATGGGTCCTCTGAGTAGAGATTCTAGGTTTAATACGGAAGCTCGCATAATTAAAAAAG
    GTGTCAAAAGTTTGTTTGAATGGTTGGCTGAGGTGTTTATCAAAAGATGGCCTACTGGAAATGACTTGGA
    GATGCCTGATATTCCGTGGCTTAGTGTTGATGAAGGGATTTTAAGACTTAGGGAAATTGCAATGCTAGAG
    TGGATATATTGTGTAAAGCATAATTGTCCACAATGGGAAGGTCCAGAAGATATGCCTTTCACTAGCTCTA
    TAAGACGCAAATTGGTGAGAGGGGCACCAGCACATTTGAAGGGTTTTGTTCTTTCCCTTTTCCTTGTACC
    AGATCTTAGCATTGGAGATGCTTCTGCTCAATTAGATGAATTAAATTCACTGGGTTTAGTTGGATTCCGA
    GGTAACAAGGGCCAGGTGGCAGCATTGAATCGCCGGAGACAAGGTGATTCTAGTTATTATAATGGACAGC
    GTAGACAAAAGAATGTTTATAATAACATACCCAGCAATGGTCAGCACAGGAGAGGTGAAATTTATAATGG
    CATGACTCGGTTGGACCTTTGGTACTGGCTAACCAATCATGGTGTTTCCAGGAATGAAATACATAGGAAG
    CCTACTGCATATTTGTTTGATCTGTATAAGCAGAAAAATTCTCAAACAAATGAAAGAAAGGCTACATTAG
    ATCATGGTAAACAGCAATCTCGGCCAGTGAATCAATTTCCAGACTTGAGACAGTTTGCAGATCCAGAACC
    CCTTGAATGAAGGGGTGGCCAGGTTCCGCTGAGGAAGGATCTTGATAAGACACCCAAAGGTTTTGCTGTT
    ACCCTTTCTCCAGTTCTTCCCCAGAGGGACCTAAGGCCTTTTACAAGGGTAACTGTACACTGGGGAAAAG
    GAAATAATCAGACTTTTCAGGGTCTGCTGGATACTGGTTCTGAGTTGACACTGATTCCAGGGGATCCCAA
    GAAACATTGTGGCCCTCCAGTTAAAGTAGAGGCTTATGGAGGGCAGGTGATTAATGGAGTTTTGACTGAT
    GTCCGACTCACAATAGGTCCAGTAGGTCCCCAGACACATCCTGTGGTGATTTCCCCAGTTCCAGAATGTA
    TAATTGGGATAGATATACTCAGAAATTGGCAGAATTCTCATATTGGTTCCCTGAACTGTAGAGTGAGGGC
    TATTATGGTTGGAAAGGCCAAATGGAAACCTTTAGAGTTGCCTCTGCCAAAGAAAATAGTGAATCAAAAA
    CAGTATCGTATTCCTGGAGGCATTGCAGAAATTACTGCCACTATCAAGGACTTGAAAGATGCAGGGGTGG
    TGGTTCCCACCACATCTCCGTTTAACTCTCCTATCTGGCCAGTGCAGAAAACAGATGGATCATGGAGAAT
    GACAGTTGATTATCGAAAACTAAATCAGGTAGTAACTCCAATTGCAGCTGCTGTACCAGATGTAGTTTCA
    TTACTTGAGCAAATTAACACATCTCCTGGCACCTGGTATGCGGCTATTGATCTGGCAAATGCCTTCTTCT
    CAGTACCTGTCCATAAGGACCACCAGAAGCAATTTGCTTTCAGTTGGCAAGGCCAACAGTATACTTTCAC
    AGTTTTGCCTCAAGGATATATTAACTCTCCTGCCCTGTGTCATAATTTAGTTAGAAGGGATCTTGATCGT
    TTGGATCTTCCACAAAATATCACATTGGTGCACTATATTGATGACATTATGCTGATTGGACCAAGTGAGC
    AGGAAGTAGCAACCACTTTGGACTCATTGGTAACACATATGCGTATCAGAGGATGGGAAATAAATCCAAC
    CAAAATTCAAGGACCATCTACCTCAGTGAAATTCTTAGGAGTCCAGTGGTGTGGAGCATGCAGAGATATT
    CCTTCTAAGGTGAAAGATAAGTTATTGCACCTGGCCCCTCCTACAACCAAGAAAGAAGCACAACGTTTAG
    TGGGTCTATTTGGATTCTGGAGACAACACATCCCTCACTTGGGTGTGTTACTTAGGCCTATTTACCAAGT
    GACTCGGAAAGCTGCTAGCTTTGTGTGGGGCCTGGAACAGGAGAAGGCCCTTCAACAGGTCCAGGCTGCT
    GTGCAGGCTGCACTACCACTTGGACCATATGACCCAGCAGACCCGATGGTACTTGAGGTGTCTGTGGCTG
    ATAGAGATGCTGTTTGGAGCCTCTGGCAGGCCCCTGTAGGTGAATCACAGAAAAGACCTTTGGGATTTTG
    GAGCAAAGCTCTACCATCATCTGCAGACAACTATTCTCCCTTTGAAAAACAGCTCTTGGCCTGCTATTGG
    GCCTTAGTGGAAACTGAACGTTTGACAATAGGACACCAAGTTACTATGCGACCTGAACTACCCATCATGA
    GCTGGGTACTATCAGACCCTGCAAGTCATAAAGTGGGACGCGCACAGCAGCAGTCTGTTATCAAATGGAA
    GTGGTATATACGTGATCGGGCCAGAGCAGGTCCTGAAGGCACAAGCAAGTTACATGAAGAAGTTGCTCAA
    ATGCCTATGGTTTCTACTCCTGTTACACTGCCATCTGCTGCCAAACATGTGCCTATAGCCTCATGGGGTG
    TTCCCTATGATCGACTGACCGAAGAGGAAAAGACTAGAGCCTGGTTTACTGATGGCTCTGCACGTTATGC
    AGGCACCACCCAGAAGTGGACAGACAGCTGCAGCATTACAACCCCTTTCTGGGACAACCCTGAAAGACAC
    AGGTGAAGGGAAATCTTCACAGTGGGCAGAACTTCGGGCAGTACACATGGTATTACAGTTTGTTTGCAAG
    AAGAAATGGCCAGATGTACGATTATTCACTGACTCATGGGCTGTAGCCAATGGATTGGCTGGATGGTCAG
    GGACTTGGAAAGATCACAATTGGAAAATTGGTGAGAAAGACATCTGGGGAAGAAGTATGTGGATAGATCT
    CTCCAAATGGGCAAAGGATGTGAAGATATTTGTGTCCCATGTAAATGCTCACCAAAAGGTGACTTCAGCT
    GAGGAGGAGTTCAATAATCAAGTGGATAAGATGACCCGTTCTGTGGACAGTCAGCCTCTCTCCCCAGCCA
    TCCCTGTCATTGCTCAATGGGCACATGAACAAAGTGGCCATGGTGGTCGAGATGGAGGTTATGCTTGGGC
    TCAGCAACACGGGCTTCCACTCACCAAGGCTGACCTGGCTACAGCTGCTGCTGATTGCCAGATCTGCCAA
    CAGCAGAAACCAACACTGAGTCCCAGATATGGCACCATTCCTCGAGGTGACCAGCCAGCAACCTGGTGGC
    AGGTTGACTACATTGGACCACTTCCTTCGTGGAAAGGACAGCGTTTTGTTCTTACTGGAGTAGATACTTA
    TTCTGGTTATGGATTTGCCTTTCCTGTACGTAATGCCTCTGCTAAAACCACCATTAACGGACTGACAGAA
    TGCCTTATCTATCGTCATGGTATTCCACACAGTATTGCTTCTGACCAAGGAACTCATTTCACAGCCAGAG
    AAGTACGACAGTGGGCCCACGATCATGGAATTCACTGGTCTTACCACATTCCCCATCATCCTGAAGCAGC
    TGGTCTGATAGAAAGATGGAATGGCCTTCTGAAGACGCAGTTACAGCGCCAATTAGGTGGTAACAGCTTG
    GAAGGCTGGGGTAGAGTTCTTCAGAAGGCAGTATATGCTTTGAATCAGCGCTCGATATATAGTACAGTTT
    CACCCATAGCCAGGATTCATGGGTCCAGGAATCAAGGGGTGGAAAAAGGAATAGTTCCACTTACTATCAC
    TCCTAGTGACCCTCTAGGAAAATTTTTGCTTCCTGTCCCCATAACTCTAGGTTCTGCTGGCTTAGAAGTT
    TTGGCTCCAGAGAGGGGAGTGCTCCTACCAGGAGCTACAACAAACATTCCATTGAACTGGAAGCTCAGAC
    TTCCCCCTGGTCATTTTGGGCTTCTAATGCCCTTAAACCAACAGGCTAAAAAAGGAGTAACAGTGTTAGG
    AGGGGTGATAGATCCAGATTACCATGGGGAAATTGGATTACCTCTTCACAATGGTGGTAAGCAAGATTAT
    GTCTGGAGTGTAGGAGATCCCTTAGGGCGTCTCTTAGTACTACCATGTCCTGTGATTAAAGTCAATGGGA
    AACTACAACAGCCTAATCCAAGCAGGATGACAAAGGACACAGACCCATCAGGAATGAAGGTATGGGTCAA
    TCCTCCAGGAAAAGAGCCAAGACCTGCTGAGGTGCTGACTGAAGGAGAAGGAAATATAGAATGGGTAGTA
    GAGGAAGGTAGTTATAAATACCAATTAAGGCCACGTAACCAGTTGCAGAAACGAGGATTATAAAGTAATA
    TGAATGCCCATTGTAAATTTACTAATGCGTTTGCGATTGTACGAGGGATAGTTATATCATGTTAGGCGTA
    TTTACAAACTTGTTATTGTTTTATGTGAACATGAGATATTATTTGTGTCAAGTTGACAAGGGGTGGATTG
    TAGTGGCTATTCCTGGTTGTCAACTTGACAATATTTGGAATGAACTACAATCCGGAATTGGAAGGCTCAC
    CAGTGACCCTTATCTGGAGGCTTGGAGATCCTTATCTGGATCTTGGTTTGAAGATCTTGAGCCATAGTGG
    CTATGGATTCCAGAAGATTGAATCTCCGAGTTTAAGGAACACACCTTTAATCTGGGCTACGCCTTTCATC
    TGGGATTAAAGGTGTGGCGGAACACACCTTTAATCTGGACTACACCTTCTGCTGGAGACAATATAAGGAC
    ATTGAAAGAAGGGAGTCTAGCTCTTGCTCTTGCTCCTTCGCCTGCTTGCTGCGTGAGACTGAGTAACTAC
    TAGATCCTTGGACTTCCATTCACAGCTGCGACTGAACAATTGTTGGGAATTGGGCTGCCGACTCTAAGTC
    ATCAATAAATTCCTTTACTATCTAGAGACTATCCATAGTTCTGTGACTCTAGAGAACCCTGACTAATACA
    TCCCTACATACAGGAAACTTGATGTATAAGTAAAGAAAATAGTAAATCTAAAAATTTCCTTATCAAATAC
    ATGCAAGAAATCCAAAATACCATGAAAAGACCTGATCTAAAAATAGTAGGAACTGAAGGTGAAGTGTCCC
    AGCTCTGAAAACTAGAAAATGTTTTCAATATTTTTCCTAACAGTGAAGACATGGATCTAATGAGGCCACC
    TCTTATAGCCATGCAAGACTGACAGTGGAGGGATAAGGACACCAATCCACCCACAAAACTTTTGACCCTA
    AATCAGTTTTATCTAAAAGCAATGCAGGGGCACAAATGGAGCAGAGACTGGAGGAATGGTCAAACAATAA
    CCTGTCATATCTGAGACCCACCTAATTGGCATACACCAGTCACTGACATTATTAATAATGTTCCATTATG
    CTTACAGGCATTTCTCTAGCATTACTATTCTTGGAGAGACTTCACACAGCATCTTATTGAAACAGATGCA
    GACACCCAGAACCAAACATTGGATGGAGATTGGGATCCTTAAAGAAGAGTTGGGAGGATAATTGAGAGAC
    CTCAAAGGAATAGCAACCCCATAGAAAGACACGAACAGGGTCAGTAAACCTGGACCCATGGGGTATCTCA
    GAGACTGATCACCAACCAAAAATCACAGAGGGCCTGGATTGATTCCCCTGGCACACATGTAGCAGAGGTC
    TGCCTTGTCCTTCAGTAGGTGAAGATGAGCCTAAGGCTTCAGAGACTTGATATATCAGCATACAGCAACA
    CCCAAGTGTGTCCCACTATCTCAGAGGTGAAGGGGTGGAGATGGGCAGAAGGGTCCTGATAGGGGACAAC
    TGCAAAGAGGCAATATTTGGGACAGAAAGAAAGGAAGAGAGAGGAAGATAAAGAGAGAGATGAAGGAAGG
    AAACAAACAAACCAAGATGAAGAGAGAGAAAAGGGGGAAAATAGCCTTGAATGGTTCAGGGATTCAAAGG
    GACATACCTAAGCATGGTAAAACAATGCACATAATGGCAGCAAGTAGCTAACACTGAATTAAATAGAAAG
    ACACATAAAGCAGTTCTACTAAAGTAAGAGACAGAGTTGCCCAATCTCACCCTATTTATTCAATAATAAT
    GTACTTGAAGTTCTAGCTAGGGCTGTAAGACAACTCAAGGAGATCGGAGGATACAAATTAGAAAGAAAAA
    TTCAAAGAATTGTAATTGGTAGATGATAGGATAATATACATAAATGACCTCAAAATTCTTCCAGAGAACT
    CTGAAAGCTGATAAATACCTTCAGCAAAGTGGCTAGAAACAAAATTACTTCATAGAATTCAGGAGCTATC
    CTTTATAGAAAAGTTAAAGTGGCTGAGAAAGAAATTAGGAAAATCACATTCTTTGCAATAACCAAAAATA
    ATATGAATTAGCTTGGTGTGACTCTAATCTTGCAAGTGAAAGATGTGTGTGACAAGAGCTTCAGGACCCT
    GAAGAAAGAAATCAAAGAACTCAAAGATGCAAAGTACTCTAATGCTCATGGATAGGCAGAATTAACATAA
    TGAAAATGCCAAATTTAACAATTCAATCTACAGATTCAGTGGAATTCCCATTAAATATCCAACCCAATTT
    ATTACATTCTTGAAAAAGCAAATCTCAACTTCATATAGAAAAACAAGAAATTGAGGGTAGCTAACAAAAT
    CCTGAACAATGAAAACACTTCAGGAGAATTCACCATCCCCTACCTCAAGCTGTATTTTAGAGCAATAGTT
    ATTAAAACTGCATGGTATTTGTATAGAAACAGATATGATGATCAATGTAATTGAATTGAATACACTGACA
    TAAAACCACACTGTTATGGACACTTGATTTTTGACAAAGAACCCAATAATCATAATAAAAATCATAATAA
    GAATGCATCCCCCAACAAATGGTCCTGATCTAAATGCAAATAGATTCATATCTATCATCCTGCACGAAAT
    TCAAATCAAAGTGAATTGCAGACTTCGACCTAATACTGGATTAACTAAATCTAAATGAACAAAAAGTAGA
    GAATAGTTTTGAACTCATTGATGCAGGATTCAATTTCCTGAACAGAACCACAATGGCTCAGGCTCTAGGA
    TCATAAATTGGTAGATAGGATCTCATGAAACTGAAAAACTTCTGTAAGGCAAAGGCAATAAAACAAAATG
    GCAACCTACAGATTGGAAAAAAAATAATCTTCAGTATCCCTAAATCCCATTGAAGGCCAATATGCAAAGT
    ATATAAAGAACTCAAGATGTTATCCTCCACAAAACCAAATAAATCAATTAAAAATGAACTACAGAGCTAA
    CAAGAGAATTCTCAACAGAGGAATCACCAATGACTGAGAATCACTTAAAGAAACATTCAATATTTGTAGT
    CACCAGAGAATTGCAAATCAAAACTACCCTGAGATTCTACTTTATACCAATCATAATGGTCAAGATAAAA
    ATTCAAATGACAGCGCATGTTGGTGAGGATGTGTATACTTTTGCATTGCTGGTGAGGAAAACAATCTGGC
    AGCTCCTCAGAAAATTGTAAATAATTCTACCTGAAGATCCAGCCATACCACTCCTGTGCATATACATAAA
    ATGTGCTCCACCATACCACTAGGAGATATGTGCCACTATGCCCATAGCAGCCTTATTTGTTAATAGCCAA
    AAGATGGATACAACCCTGATGTGCCTCAAACAAAGATTGTATATAGAAAATATGGGTTCCCTTACACAAT
    GGTATTCTACTCAGCAATTAAAACGTGAGAACATCATAAAGTTTTCAGGCAAACTGATCAAATGAAAAAG
    TATAATCTTGAGTGAGGTAACAGAACCAAAATGACCTGCATGGGATGTACTCACTGGTAAGTGAATATTA
    GACTAAAAGTATAGAATATCAATGATGAAAGCCACAGACCATAAAGAGTTTAATAAGATGGAAAGCTCAA
    GTACGGATTCTTCAATCCAATATAGAAAGAGGGACAAAATAATCAGGGGAGGCAGAGGGAGAGAGAGACA
    TTTGGTGGAAATGGGAGAAGAAGGGAGAAAGGCAGAAAGGATCAGGCGTTGGGGAACACTGGAAAGCAGC
    CCAGGGGTCCTGGTAAATGGATTAAATATTCAGCTGAATGGAGGTGGGAGGCAGGGGGAAGCTCTGCAAA
    GTCCAAGAGACCTGGGATGTGAGAGGCTCCCCAGATGATAATCTTAGCCTTCATGCCTAACAGTTGTAGA
    TAAACCCTGAAGAGATCACTTCCAATAGATGCAGAGGGCCCTAAGTGGTTGGATGGAGTCCCCCAACTTA
    CCTCAAAATTGTCAATACTCATAGAAATTAGGACAATGAAAATCAAAACACCCTGAGATTGTATCTTATG
    TCTGTCACAATGGTTAAGACCAAAACCTCAAGTGATGGCTTGTGCTGGCAAAGATTCAGAATAGTAAAAG
    TCTCCCCATGGCTTGTGGGAATGCAAACTCTTACAACCTCTTTGGAAGTATATTTGATTGTTACCTGGTA
    TAAAATGGCAAAAAAAAAAAATGGTTGAAGGGGGACTAAAAAAGGAAGAAAGGGGAGAACTATGGGATGC
    GAAACAAGAAAGTTTGTTGCAAAAGAAATATGTTTCCACTGCAAACCCTGAGTCTCAGACAGAAGGGGAC
    CTGGAATTCTTCAGATACAAAGAATCTCTAAACCCTGAGGACATTCTATCACAAATAAGTAAAATTCAGA
    AAATTCTGAGTGCTCCCATCACGGAGATGAATCTGCTATGAACAGCTCATAGGTGTGACCCTCTACAAAA
    GCCATATTATTGAAAAGCCACATTGTGCCCAGACTTTGGAAAGACTGAGCTCATATCCTGAAATACAGTT
    ATGTGTGGTTCTATTTAATTACACATTTACACTAAGAAAACATGGCAGTATGGGAATGAAGCTTGTTCTG
    TACACATTAACAGAGGGAAACTAAACAAAGTATGGTGAATCCCTAACCAAAAGTAAAAAAAAAAAAAGAA
    AGAAAAGAAAATAAAAGTGAAACTACAATATGTTTCAAATGCTGTAACTGAAATCTGGTTTTTTGATGCT
    TATATCTGGTATCATCAGTGACTTCAGATTTAGTCCAACTCCAGAGCATGGTATAGCAGAAAGACATGCA
    AATAAGCCTTCTCTCTGCCCATGAAAAACACCTCGGCCCTGACCCTGCAGCTCTGACAGAGGAGGCCAGT
    CCTGGATTCGATTCCCAGTTCCTCACATTCAGTGATCAGCACTGAACACGGACCCCTCACCATGAACTTG
    GGGCTCAGCTTGATTTTCCTTGTCCTTGTTTTAAAAGGTAATTTATTGAGAAGAGATGACATCTGTTGTA
    TGCTCATGAGACAGAAAAATTGTTTGTTTTGTTAGTGACAGTTTTCCAACCAGTATTCTCTGTTTGCAGG
    TGTCCAGTGTGAAGTGAAGCTGGTGGAGTCTGGGGGAGGCTTAGTGCAGCCTGGAGGGTCCCTGAAACTC
    TCCTGTGCAACCTCTGGATTCACTTTCAGTGACTATTACATGTATTGGGTTCGCCAGACTCCAGAGAAGA
    GGCTGGAGTGGGTCGCATACATTAGTAATGGTGGTGGTAGCACCTATTATCCAGACACTGTAAAGGGCCG
    ATTCACCATCTCCAGAGACAATGCCAAGAACACCCTGTACCTGCAAATGAGCCGTCTGAAGTCTGAGGAC
    ACAGCCATGTATTACTGTGCAAGACACACAATGAGGAAATGTTACTGTGAGCTCAAACTAAAACCTCCTG
    CAGAGCACCCAGGACCAGCAGGGGGCGCAGAGAGCACATGGAGTTCTGATTCACAGAAGAGTTACAGCCT
    GTACAATTAGACCCAATCTTCAACAAACCGTCAAAATATTCGATCCAAAATTGTTCCTGTCTAAAAGTAA
    TTCAAGGACAAAATGGACCAGAGACTGAAGAAATGGCTGACCTGTGACCCTCCCAACTTTGGATCTATCT
    CATAGGCAGGTACCAAACCTTGACATTTGTCACTGACACTGTATTGTGCTTGCAGACAGGAGCATAGCAT
    GGCTGACCTCTAAGAGGCTCTGCAAGCACCTGAATGAGACAGATGTAAATAGAGTGTACAACTGGATTAA
    GTTTGAAGACTGCAATGGAAGAGTTAGAGGAAGGAATGAAAAATCTGAAGGGGATCACAACCCCAGAAGA
    AGACCAACAGTGCCAATTAAACTGGATGCCTGGGAACTCCCAGAGACTAAGCCACAAACCAAGAATCATG
    CAGGCTGGTCTGAGAATCCTGGCACCCAAGTCTCAAGGAACTGCCTTTTCTTGGCTCAGATGGGAGAAGA
    TGAGCCTAAAGCTTTAGACTTGACGCCCCAGGGATGGGCAATACAAAGTTGAGTTTCTTGGGAAAGTGAA
    GAGGATGGTGGGAGGAGGAATAAATCTGGGAAGTGGGACTGGTTGGGGACAACATATTGGTCCTAAATTT
    ATGAAATAATTATCTAATTGATAAAAAGAGTCCTTGGGGTAATGGAGGGCTAGACTCCTCTGTGCCTAGT
    TTGTAACTCTACAGGGATCCTCTTTAAAAGAATAGGGTGCACATAGAGTATATGTGTGTGACACTAATAC
    AGGGGTAAGTGTTTCTGTAAGAACTTTATGAATAAACTTTATTAAAACATCAAAAAGTATAGGTTGTAGC
    AACCCTTGACCTGTACGAATGTTTATAAAACTTTCTATTTTCCTTAATTATATCTGTTTTGCATTTGTTT
    ATTTATTTATTTACTTACTTACTTATTTATGATTTCACTGTGTCTTTCTGTAGTCCTGTATGTGTTTATT
    TGTCTCTTTATTGCTCTGTTTCTGTTTCTTTCTCTCTGTCTAGTATTGTATCTCTCTGTGTCTCTATGTC
    GCCGATTGTGTCTGTGTGTATGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGTGCATATTGAAA
    TGAGATCTCTTCTTCTATCAGTGTACATAATGACTTTGAAATAAAGTCCATCACTGGGCTTGGATATCAC
    TATCTTGTTAGAATGGTTGCCCAAAGTGTTCCAACCATCACACTGTTTCTACATATAATAGATGGGTTTA
    TTGATTTACTACCAAAACTACCCCATCTTAAGTTATGGATATTAAACACAGATCCTCATGGTGTGTTAAG
    AACTTGAAGCACAGAGCTATATGTACAGCCCACTAAAAATGACTTAAATATAAGATAAACTCTGGCTTGA
    ACAAAACACAGAGCATCACACGAGGCAGAAGTGAATCTCTATGAGGACCAGGATCACATCCCAAAGAACC
    AAAGAACACTTGAGACTGTGGAACCCTAGAGTCAGGGCTGACACTCAGTAAGATTTACTTCATAGAGCAT
    GATGTGGGATTCAAGAAGAAATCAGGCAGGGCCTGTGACCCATGAACCAGATGACTTCCAGTCTCTCCAT
    CATCCTCACACAAACCATAGGCAACAGCTCAGCACTGACTCACCTGTGATGCTGGTGACAAAATGTGTGC
    AAAGCCTCAGAACTGAGACGTGAGGCCAATGTTGCTACCGACACTCAGTGAGCTTCAATTTGCTGCAAAC
    TGCTCCAAAACAACTCAAAGGGTAACTTCTTCTTTTTCTATTTGTACTTGTGATGCCTTGGTAGATATAG
    TTCCCCAATAATTTAATAGGACAAATCATTTTTCCTTTTAACACATTAATCCCCTTTCCTTCCCCCAAGA
    TTCTAAAATTTTTCTTTAACACTGATGTCTGAGAGATATGGCATAATAGATGTTTGTCTTATTCTGAGTT
    GTTCCTTATCAAAAGAAATCAGCTGTGGCACTTTGAACCTAAATATAACAATATTTCACAAAGGCATTCT
    GGGAATATATAGATGGTATTGCTACAAAAGAATAGGAGGATCTATGGCCATACCACCCTTAATGAACCAG
    ATACTATCTAAAAGATTAGGACAGCTGGGCATGTTGGCACAGGCCTTTAATCCCAGCACTAAGGAGGCAG
    AGGCAGGCAGATTTCTGATTCGAGGCCAGACTGGACTACAAAGTGAGTTCCAAGACAACCAGGGCTATAC
    AGAGAAACCCTGTCTCGAAAAAACAAAACAAAACAAAACAAGAGTAGGAGGGTATTAGATGCGAGGTGAT
    GATGGCCATTCAATCAAACCAGAATGTGACCTGAGAAAAGGTCTAAGTTTGTCAGCTTGTCCTGGAGATG
    TGTTGCCTCTGATAAATGCAGAGCTGGAACTGCAATACATTGGATTCCTGTGAGTTACGGAGAAATAAAA
    GGAATAGCCTCTGTTTCCTTTGGTTCATCAAGTTGGCAGTGAGCTAGAAGATGATACTGGGAACCATCAC
    ATGTACTTCTACAGAGTTATTCTACATTCTACAAGTCAGTCTTGCTTGCTTTCGTTTCTGTGAGGAGCTA
    AATACAGAATGTTTTCAATGTCTCATAATGTTCTGTGCACACCCATGGGTGCCTAGCCAAGGATAGAAAC
    TTGTATCTGATAAGGAAAGAGGATGCTGCAGTGGCCACACTCTGAGATCACCTCCTGCCAAATTATACTA
    GAGTGTTTTACATAGTCTTGAAAACACTAGGTCAAATATGTTGTCATCCAGATATGAAAACTCTGTGCAA
    CAATTCAGAAATACAGTGGTCAGGACAACTGGTATGTAACACTTTAGTTCCAGCCCACATTAATCTCACA
    TCTTTTCTGTGGTTTCAATAAAGAGCACACATGTTTGGAACACCATCTCCACTTTGTATGCTTATCCTTA
    TGCATCAAACTTTTCCTGTAATTTCCTACCCCGCACAGGTTCCTGTCTTGATCTCTTTTTCTAATGAACA
    GCAATACAGAAGTGTTGGCCAAATGAACACTTTCACCCCAAGTTGCTTTGCCATTGTGTTTCATCACAGC
    ATTAGTAACTCCCAGTAAGGCTACTGGTTACCCTGCATCTTCTATGTAGATCTTTTGATGAAGTTCCAGG
    CTTGGGGTCTTTATCTGACTGTTATCCTGGTTAATTCATGTCCACCAATAGAATATTGTTCTCATTTTCA
    ATATCATATGAAGTTACCTGTTTATAGGATCTTCCTAAAGCAGAAAACTATATAAAATGTCTGCTTACTT
    TAAGAAAAGTATGTGTCCTTGGAGGTAAATGGAGGAAAGGGTGGAGGATGTTGAGTAATGGAAGACTGGC
    TAATACAGGAAGGTCACAGAATTGAATGATTTTAAAAATTTTAACTCCTCATCAATGAGGTACTTCAAGT
    TGAGGCAGGAGTCCTTGATGCACAGGTGACCCAAAGGCCCCAGCCTCTGTTTCTTGGTCTGCTCCAGTCT
    CCCGGCTCAGCACAGTTCACTGAGTGACAATCTTTAAGATAGTCTTTCAGGATACAGTTATCACAGTTTT
    CAAACTCTCTTCATTGAAACAATATAATGAGTCAGAGTCCAGTGTGCCATTAATAGGCCCTATGCAATAG
    GATTTTACTTCATCTGTGGAAAGAAACCACCATGGCCTCATCAAGGCCTCATTTGATGATTAGTGTAGAA
    AGCGTCCCCAGAGCTTTGCTGGGATGAAAACCCTGGCAAGATGTTTAGGGCACTCTCCATCTGACAGGAC
    AATTCTATCAAGGGTTGCTTCCATATAGAGAGAAATCTCCACATCTGCAGTATTTCCCGATTTATCAACA
    GTTCTTTACCCCGTGTCATATGCATAAAATCTTTTCTCTGTAGAATTTTCAGTACTAAAAACTAACAAGG
    ATGTTGGTCCTGATATCAGACATAATAAATAAATAAACATCAAATTATACCCTAAACATGTGGAGATGGT
    TTTCTGTTATGAATTTATTGGCTCTCTAAAAAGTGTTAATTAAGCCAGGCGTGATGGCACATGCCTTTAA
    TCCCAGCACTTGTGAGGCAGAGGCAGGCGAATTTCTGAGTTTGAGGCCAAACTGATCTACAGAGTGATTT
    CCAGGACAGCCAGGGTTACACAAAAAAACCCTGTCTCCAAAAAGTAACAAAAAGAAAGTGTTAATTAACA
    TCTACACTTTAAGATAATTTGGTGGCAAAGGTTAATAGTCTGAAATACTAGATATGAAAGTATGACACCT
    AAATTGCATGCAGAGAATAAAGCTGAATTCCAATGAGATTCATGCCTTGTGAATCCATTCCAATCTGATC
    TCAATCTTCAAACATGTTTGTGCATAATTTACATCTTAATCAGTTGCTGGAAATTAAAAGGACATAAGCT
    AAACTTAAAACTCTTTCTATTTAATGTGTCAGAATAGAATATGTGCACTGAAGTTTTCATGTGCATAGGA
    TATCATTGTTACAATGATGGTTCAAATACGCACCAGTAGCACAGGTGATGCTTGACATGAAAAAAACTGT
    GACCAGAGCCCAGACGTTGATGTTGGCTGAAAGAGCCTAGTGTCTCACATTTGATCAAGCAAAGTGTTAT
    TCAGAGAAGCAGTGCCAGATTTGGGATCCTTCTTAATGGATCAAGAACATGAGGAAGATTTGGAAGCCAG
    ATTGATGAGATTACTAGAATCCTGGATCTGAACACACAACACACAATAGTAAGTTGAACTTTTCCACGCA
    ATGCTAAAGATAAAGCATCCAGTATCATGTTATACAGGACCAAGGTGAGGATCAGTCTGTGGGTGAAGTA
    CAATGAACTGGAAATTGTTTGGATTTTAAATGTTGGTTTTTAAATTATATATAAAATATATATATATATA
    TATATATATACATATATATATATATATATATATATATATATATATCGGAACCAACATTTAAAATTTGGAT
    TTTAAATGTTGGTTTTTAAATTATATATAAATTATATATATATATATATATATATATATATATATATATA
    TATATATATATATATCGGAACCAACATTTAAATTCCTAATTCTTAAGGACTTCACTTTTGACCAAAAATA
    TTTGAAATGGGTTATTTAGGTCTGTGGTGGTTTGAATATGCATAGCCTATAGGAAGTGGAAGTATGGCCA
    TTTTGTAGTATGTGTAGCCTTGATGGAGGAAGTACATCACTATATGGTGTTGTGAGAGTTGAGATCCTAT
    GTTCAAGTTCTGCCAAAAACAGAAGAGAGTCCCCTCCTGGATATTTGAAACAGATGCAGAGGCCCAAAGC
    CAAACATTGGGTATATCTCAGGGTTTCTTATGGAAAAGTTGGCTGAAGGATTGAAGGCCTTAAAGGGGAT
    AGGAACTTCACAGGAAAACCAACAGATTCATCTAACCTAGACTCTAGGGGTCTTTCAAAGGTTGAGTCAC
    CATACAAAAAGGACACAATGGCTAGACCTAGGTCCCTGATACATATGTAGCAAATGTGCAGCTTAGACTC
    CATGTGGATTCCCCAACGACTAGAGCAGGTATTGTCCCTGAAGTTATTGCTTGTCTGTAGAATACATTTC
    CCAACATAATTGTCTTGTCTGGCCTCAGTAGGAGAGTATGTTCCAATCCTGGAGAGACTTGATATGCCAG
    GATTGAGAGATTAAGGGTCTCCCACCATCTCAAAGTTCATGGGTATGACAGGGGAGGGGCAGTGCAGGTT
    TTCCCCATCTCTGATTTCCAGCATTTGCACCCCCAATATTGAGGGGGAGGTCTAGCAATTGGAGGGGGGA
    CAAACAGTATGAGAAAGCTAACTTTAGTGGTGTTGTCACAGTGTGGGGTATTGTGGGTGGGAGTGGAGAT
    GAATCCTCCTCCTCCTCAGGAGGCTGTAGCAGGTGCTTGCCCTCTTTTGGGACAGTAGAGCTGTGGTCAG
    TACTGGCCTGTTCCTGACAAATTTATTCTGTGCTGTGACCATTTATTCAAGGGAGGAAGATTTAAGACTT
    GCTATGATAACCTGACGAATCTGGACAAACAAGAGACAGGAGGTAACACCTGAGTTACTCTTTTGCTTGC
    TAGTACAGAAGAGCACTATAATCCACAAATTGGGGTCCCACATATTCTTGAGTGGGATCCAAGGTGCCAT
    AATTTCAGCCACATTCCAAAGTCCCTCAAGGTCTGACAGTTTAGTCTTTAGGCTTCTCCTAACCAAATCA
    TATTTGGAGTTCTTTAACATAAAAGGGTAGTTTCCCCATATCACTGCCAGCAAAACAGGTTGAATTTGGA
    CAGACAAGCAAAACTATCACAAACAAGACAGACTATGTGTGCGATCCAAATGTCTTGTGATTAGAGGGGA
    AGTTCTGCAGCTTATTAGGCTGTGTCCTTATGCCCACAAATGTCTTCAGATAGGAAAGGGCCATTGGGTG
    CCAATCCTTAGTTCTTCTGTTTCCTGGGCTGTCAGTTTTTATGTGGAGAAGACATGAACCAAATGCAAAG
    TCATGTATCCTACAAGAACTGACATACACAGACAAACAAGGAATAACAATGAGCTCTCTCATTCACCTAA
    GGGGGTCTTATAACATAGAACAGAAAGGGGCCAACTTAGCAAGAATTGACCAAAAGGTGGTCACCTAGAC
    CACACCACAATGCAGGAAGGATATCAATGAAGGAAGAACAAAGGAAAGGCCAAATCAAGTTTGTTGGCAC
    ATGACATAAAACAGTGCTCAAAAAACAATAGATGCGAGCAAAATGAAGCATTGGAATCATATCGGGGTAC
    ATAGGGGTCACTCTTACCCCTGTTCAAGTGCCAGATGTTGTTTTAGCCTTAGGCTCCCTGAGTTTGTCTT
    TAGGGGAAATGGGTAAGAATACACAAAAATAATGTCACAGAATCTTAGAGGCAGATGAGAAGTCAAAGCA
    GACTCATTTATTGCTATAGAAAAGAATGCCTTTATACCTTCTGTCCATAACACCTCTGCCCATATATGCT
    CATCTCTGTGAGGCAATGGACTACCTGCAGACAGGCTGGTATCCAGTCAAGCTGAGGTCTGAACCACAAT
    GGTCGTAACTCACCTAAAGGACGTGGTAGGCATGACGCGATAGGCGTTCCCTCATGCTCCTGGAACTCCG
    GCCCCTGCCTAAGGTACCACCTCCCACAGCCCCCACAAGAGAAGCATGGTCAGTAGTCATGTAAGCAATG
    GCCCAAGCTTCTGACCTTCAGCCTAAACTCCTCCCCAGTTACCTAGCAACAGTGAAGACCATAAAATGGG
    ATGTTAGGCCCCCACCTCACTCTCTTACTCCTTTGTTCCTTTACCTCTCACTTCTCTCAATTCTCTCTCC
    TCTTCCCTTTCTTTGTCTTCTTCTTTCCTTGTCTCTCTGTCTTTCTCTTTCTCTCTAGCCTTCTCTGCCT
    CTCTCTCTCTCTCTGTCTCTCTGTCTCTCTCTTCTCTCTTTCCCTTGAATTTCTTTTTTTCTTTTTTCTT
    TTTTTGATGAGCACAGTATAAATAGTTTATTGCATTGTTTCTGAATGTGGCTGTATTCTCTATTGTTCTC
    TTTCTTATTTTTTTTCTTTTTTTGGTTGTTTTTGTTTTTATAGTCTCGCACAGAATTCTACATCTACCAA
    ATCCCCATTGTGTACTTTAGTTTTGTCTTGTATTCAAAGGTTCTTTCAGAAAGAATCTTAAAGATGAAAT
    TTGCCTTCCAACTTTTCAAAAATACATATAAAGATAGATGTTACATAGTTCACGGAATAGACACATATAC
    GGAGATGCAGCAATATCTCCTTTGTGCCTCTTGTATATTCATGTTATTTCCTCAACTAAAAATACATAGC
    CACAAAGACATACAATGAGCACTCCACTTAGGAAAATATGGCCATATTTTTTTACATTTTTATGATTTTA
    TGATTAGGTATATTCTTCATTTACATTTCCAATGCTACCCCAAAAGTCCCCCAACCCTTCCCTCACTCCC
    CTTCCCCACTCCCACTTGTTGGCCCTGGAGTTCCCCTGTACTGAGGCATATAAAGTTTGCAAGACCAATG
    GGCCTCTCTTTCCACTGATGGCCCACAAGGTCATCTTCTGATACATATGCAGCTAGATACATATACATAC
    ACGAGCTCCAGGGGGTACTGGTTAGTTCATATTGTTGTTCCACCTATAGGGTTGCAGATCCCTTCAGCTC
    CTTGGGTACTTTCTCTAGCTCCTCCATTGAGGGCCCTGTGATCCATCCAATAGCTGACTGTGAGCATCCA
    CTTCTGTGTTTGCTAGGCCCCATTATAGCCTTGCAAGACAGCTATATCAGGGTCCTTTCAGCAAAATCTT
    GCTAGTGTGTGCAATGGTGTCAGCATTTGGGGGCTGATTATGGCATGGATCCCCGGATATGGCAGTCTCT
    AGATGGTCCATCCTTTCATCTCAGCTCCAATCTTTGTCTCTGTAACTCTTTCCATGGGTGTTTTGTTCCC
    AATTCTAAGAAGGAGCAAAGTGTCCACACATTTGTATTCATTACTCTTGAGTTTCATGTGTTTCCCTTGC
    ATTTCTATAATAAACCATAAGGAGTCTCTGCTCTACCAAGACCCGCTGCACACTCTGGTCAGTGTTGGGA
    ACTTTTCCCCTATTCCCTCTCTCCTATAACTCCGGGGCTACAGGGTGTCTCCTTTGGGTCCCGGTTGGGA
    GCTGTCTCTTCTCAACCCCCTGACTCATGGGTCAGAGGCCTAAATCTCCACCCAAGGCTGTGTGAAAAGC
    ACCGGGTGGTCTCCCCATATCTCCCTGTCCAGAGCACAGGAACTCTGGCCGGACATGGCATATTTTTCCT
    CCCCAACTTCTTCCCCGGCCTCCTCAGGGCTGTCCCTTCATTTTGTTCCCCACACATCTCCACATGGCTG
    CCACCATCCAATTGGCTGCTGAGGTCACACACTCTGTCTTTGTTCTTCTCTGAGTCTCATGCAGGTTTTG
    TGTTAGTAAATGCAAAAGTGCCTGCTGTGCATGCATGAACCATTACAGGCTGCTAGGCAGAACATGCTGA
    CTTGCTCCTGGATTATAAATCCATCACTGTGATAGCAGGACATATCCAGAAGACATTATTTAACAACACT
    CCTCTTCGTGCTCAACCTCTCATGGTCTTTCTACCTCCTCTTTCTTAGTGTTCTCTGAGCCTACATGAAA
    TGTGAACAAACCTGAAAAAAATCTCTGTGTCAAATACATAGTGTGGATTGGGAAGGAAAAACCCTGCACT
    TGTGTGTGGGCAGGGAAATGCTGGTGCTTTAACAGGACAAGTGCGGTGTGGCTAGAGAAAGTGATGAGAA
    GAAGGGAAGCATGAGAACTGGGTGGGTGGATCCCATGTCTACTGAAAATGCTATGTTGATGTCAAGATAT
    TGTGTCTTGTTACAAAAATTCATTGAGTACCTAGGTTATTCTCAGTATATAAAAGGGGAGGAATGAAACT
    AGAATTAAACACACACACACACACACACACACACACACACAAACACACACACACGAGTAGAGAAAAGAAA
    TAGTCATGAGTTGCCTAGTGAATGAAGAGCGGAAAATGGTGCAGTTAATAGGGATCATAGAAAGAACTGG
    GGGATGCACACGAATGGGTTTCCTGTAATTATGTCTTCATAGTAATCTCTGCTCAATAATCAGACAGTGA
    CAATGTATGCCTCATTTACAAGCCCTGATGGCCTCTCAGAGGAAAGCATCTCTCTGAAATGAATAAAGTT
    CAGAAATGTCCTAAGTGTCCCTGTCACAGGAAAGCAGTGTTGGTAACGTTTCCAGGAAGCTCAGTCTTTG
    TCAAATATCCACAACAAGAAGAAGCCATGTCTAGACAGACAACAGACTGGGAAAGACTGAGCTCATGTAT
    GGAAACACAACTATGTGTCATGCTTTTATTTTCACATTATACTGAGGGGATATGACATTATAGAAACACA
    GTTTGTTCTTTGCATATGCTGAGAGAGGAACTAGATGAAGTGTGCTAATTCTTAGCAATAAAAAGATATA
    CAAAGTGGTACTTTACTGTTTCAATTTTTGTAACTGGCATCATTGTCTTTGATATTTTATATCTTCCTTG
    AGCACTGCCTTCTCTCAAGTGTCCAACTTCAGAGTATGCTATAGCAGGAAGACTACCAAATAAGATTAAT
    TTTTTTGTACCCATGAAAAAATTATGTGCCCTGACCCCTGTTCTCTGAAAGAGGAGCCAAGTTCTGGATT
    CCCAGATCCTCATATTCATTGATCAGCAGTGAACACAGATCATTCACCATGGACATGGGGCTCATCTGGA
    TTCTCCTTATTGTTTTTAAAAAAGGATTTCATTGGGAAAAGCTGCCTCATATTTCTATGACCAGGAGAGG
    AAGATACAGCTAGAGACACAAGCCCCACCATGTAAAATCTGTATGGTACTCTCGTTTTCATTTTACAACA
    TTTTGCTTTTGCATTGCAAAGGAGCAATAAGGGTTCAGCAATCAGCACTGTAACTGTACTTTTAAAATTT
    CCACCTCTACCCTCTGTGTCCTCTATCTAGTGATAGAAAGTGAAATAAGCACATAAAGCATGGGACAAGA
    AGAACACACAGAGGAGCAGAGACTGGCTACAAGTGGCAGCCAGCATGGAGCTGGACAGAATTTAAAAAGA
    TAAAGAGAAATGTCATGGCATGAAGCAGTGACTTTTTCTGTTCACAATGCCTGCAAAAACTTTATGGAGC
    CTACTACTGCTGAGATATGCAGGTTTGGTTCCAGAGAGGATTTTCTGTTTTATTTAATTTGCTTTTAAAT
    TTTTCTTCTTTGTATAGTCTGTATTTTTAAAAAGGGGTTGAATGAATACCTAAGCAGTTGGAAAATTTGT
    GAGTAGAAACCGAGGGCCTGAGAAACAAATAAATCAAAATTTTGAAATGGCAAAAGAAAGGGTTCATTCT
    ATTTTCTCTTTTCAGAAAAGGTTGCAAAGTTGGATGTGCAAATGGAGATGTTATGGGTGGACTTGGAACA
    TCTTGGGAAGGAAGGAACCCAGGAAAAGAAAGAATGAAATGGCTCAGCCTCAATGACTGAGCAAGAGAGT
    TAGAGTCACCCACAGGAGAAAAGAAGAAAATAAACAGCACTGGGGTGAATTTGGGTCAGAGAAAACCTTA
    AAATGCCAGAGGACAATGTGATGAAAGAGACCATTTGAAAGAAAGGGTTAACCTCATTCCATCAGTCATG
    CCAGAGTTAGAGAATGGGCAGTCTGGAGTTACAAGATCACGATTAGCCTTCCCAGTATGTATACAGCATA
    TTCCTGATAATGAGATGAAGCAAAGTTTGACAAGGTAAGATTGTATCCTATAGTAATATATAGATCAAAG
    GCATGTTGCAGTAAATCTCCAACAGAAATAAGCCCGGGCAATGAAAACACAACTCAATTAATATGAATAC
    GTGCTGTGCACCTAGACTGGGCAGATCTACCACTCCACTACCATATGAGAGATCCCTTATAACTTGTGGT
    TTCTCCAGGCCAGCTGCTTCTGCTCTACTTTCCTTCCTCCTCCTCCTATGTCATCCTCTCCCTCACTCTT
    TCTCTCCCAAAACTTTCAGCTGCACCTTCCCCTCTTCATCCCCCAATCAGTGGCTCTAGCCTTTATTTAT
    AAATTAAGGTAGGAAGAAGGTTTATAGGAAATTACCTGAGTGTTGACGTGTTGATAACCCCACACAAGAG
    AACAAAATTAATATCAAATATGATTAGCTCCAGGGTTATATGCAACAAAGGCATGATAAAGTGGTCATGA
    TTTCATATGAGATGTACTGGACTCATGTGAAAAAACGTTTAAATACATGGGCTTACTCAAAATATAGACT
    CATACCCCCAAGATGGGAAGAGACTGGTAACATTTGTACTGGAGGCTGGTCTGCTGTGGCAGCCATTAAC
    ACAGTGGAGGGAAGAGCCTCAAAGAGTGAAATAGAGGAAGGGGAACAAATACAGTAAACCACCAGTTACT
    ACTTAAAGGGCAGTGTTCTGATGTCCTAGGGAGGGCACTCCAAAATACCAATGGCCTTATCCTTAAATTT
    ATTGTTTAATGAGCCTACACTGATCTCAGTGGCCCACTACTAAGGAGAAATGACAGGCACTTGAACAGCT
    GATATGAGAACAGCTGGAGGCACAGTATACAGAAGAGTTTACAAGCCTATGGAACTCCCCTGTATTTTTT
    TATGATGAGGAAATCTGAAAAATGTAAAATGTTGAAAGATTTAAGAGCAGTTATTAGAGTAGATCAACCA
    ATGAGTCTCTTGCAGCCTGGAATTCTTTTATCTTGTTTGTAACAACAATCAGGCTCCATAAATTATAAAC
    TATAAAAATTTACTTTATAAATTATAAATATATATATATGTGTGTCTGTAGATAGATAGATAGATAAATA
    GATAGATAGATAGATAGATAGATAGATAGATATATGGATTTGATGGTTGCAGCAAATTCTAATTGGTTCC
    AACAACCCTACTCACATAATACATTCATACAGGTTTGATAGATGGAGCTAAGTTTTAAATAAATTATTTT
    TCTCCCATGGCTTATATATACACCACCAAAATTCTCAAAAATTAAAATGTGATTGTGTTGTATTTTTCTT
    TTACTGAATGACTATAAAAAGTTACAACATTCTCCATAAATTTACATGAAAAAATATTATGTAGTGCAGG
    TAAAGAAAACAAATTGACCCAAGAATGGTGTATATTCATTACTAAGCAACTTTTTAGATTCACAAAGTGT
    GGGTAAACAAGGTAATTTTTTCAATCAGTTTTTTTTAACTGGCAGGCAGCAATTCAGAGTTACAATGAGA
    AGATTAATAATTTTATTGTGTATTTTAAAATAAATCTTACAAAAATATTAATAGAATCACAAATTTATAC
    CTTTGTATAAAAACAATCAGTCATTTCTACTTTAAGAAACAGAACTCACATCTACTCATCAATCATTTTA
    TTAAGTCATATTACAAAGCTGAGTGCTAACATGGGTATAAGAAAACCATAACCTTATTCACCAGCCCAGC
    GTCAAAAAGAAAAAAACCAGTCATATCAGCTGCTGCTTCAAGAGTTCTTGTTCCTTGACATTAACAAAAT
    CCCTAGCTTAACTATTAAATTTTTTTTCAAAACTTCTAATTGATCCCTTAGATAAATGTTTGTGCTAACC
    ATCGGGACACATCCCATGAGTTCTGAAGCAGTGTGTTGTTCTTCATGCATGGCCCTTTTGTAGAGCTGTG
    AGTGTAGGGGAAGAGGGGGGAGAGAGAGCCCGTGTCCAGCCAGAGATCCTGTGCTCTGGGCAGGCAGACA
    CGGGAGGACAACGGAACACTTTTCACTCGGCCTTTGGTGGGCATCTGGCTGTGTGAAGTTACTGACCCCA
    CATGGTGGGGGATGGACAAGGGGCAGCCCCTGGTACCAGGAGCCCCAGGGCTACACTCTCGGCCCCAGAT
    ATACAAGAAGAGGGCAGAGGGAGAGAGGCTCCCACACAGGCGAGAGTCCTTAGTCTGGTCTGTGGCTGGA
    GCAGGGGAATTCCTTCTGATTGGAGATTAGGCACAGCTGATTAGGGGAAAGCCTACCCCATCATCCAAGC
    ACAATGGACTTTGAGGAACAGAGCCAGTCTAAGCTTTTATAGCTTTATGGTAGAAAGGCAGGGAGAAAGG
    AGAGAATGTGGAGAGAGACAGAGAGAGACTGGCCATGGCCAAGAGGAGGGAAGGGGGAAGAGAGAGAAAC
    AGGAAAAGCTAGAAAGTAAGATAAGAGAAAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGCAAAGTG
    GGGCCAAGCAGCCCCTTTTCTAGTGAGCTTGTCATCTCACAGTTGCTAGGTAACTGGGGAGGAGTTTAGT
    CTGAAGGTCAGAAGCTTGGGACCTTGTGTATGTGACTACTAACCACAGCTTCTCCTGTCGGGACTGTGGG
    AGCAGTAACTTTGACAGGAGACAGGGATCCAGGAGACATGAGGGAACACCTTCTGTCCCACATAGGTGGA
    ATCGGTTGTACCAGGGTTCAGAACTCAACTCCACTGGAGACCAGCCTATGTGTGCATAGCCCATTGCCCT
    ACAGCCTTTGACATTCTACAGAGTTCTGAGACTGGTAGAGATACAAAATAGCTAGGATTACACAGAGAAA
    CACTGGCTTGACAATAAAACTTCCAAAACAAATATAAATGAATAAATACACAAATTGGAGCAAGTGAACT
    TGCACTAAATCCATCAAAACTTGCACAGGATGGCTGTCTCCATAATGTTCAGATCTACTTCTATTAATGT
    CATTAAGAAGACAAAGATTATGCACAAAAAGAAACAAAACAAGAAACCCAAAAGGTAAAGGCTCCAATTG
    TAAGTAATAGACCCACAGTCTCTGAGGCCTGACTGTGCAGGTCCTCACCTTTGGTAATCAGCACTGAATG
    CAGACCACTCCTCATGGACTTTGGGCTCAGGTTTGTTTTCCTTGTCCTTATTTTAAAAGGTAATTCATAG
    AAATGAGATCCTGCCAGTATTGTGTACATGAGAAATAGAAAAATTGGTTTTCTTTGCTCTATTTTGTTTT
    GTTTGGTTAATGACAGTTTCCAAATCAGCATTCTTTGCTTTGAGGTGCCCAGTGTGAGGTGAAGCTGGTA
    GGGTCAGGGCAGCCTGGAGGGTCCCTGAAACACTCCTGTGCAGCCTCTGTAGTCACTGTGAGTGACTACT
    GAATGACCTGGGTCCTTCAGGCTCTAAAGAAGGGGCTGGAGAGGGTGGAAATAATTTTTAATGGTGGAGG
    TAGCACCTATTATCCAGACACCATGAAGGGCTGATTCACCATCTACAGAGATGATGCCAGAAACACACTT
    TACCTGAAAATAAACAGTCTGAGGTCTGAGTACACAGCCATGTGTGTGTGTGTGTGTGTGTGTGTGTGTG
    TGTGTGTGTGTGTGTGTGTGTGTGAGTGTGTATTCATATATATATATATAGTGTGTATGTATATTCATAT
    ATATATGTATATTCATAAGGTTGAGTAAATGGACTTAAACTGATTCCATCACAACTTCCATGGGATGGAT
    ATTTCCCAGTGTTAAGACCTGTCAACATCACTGTCATTCAGGAGACAATGATTATGCACAACAAAACAAG
    AAACCCAAAAGCAGAGGACTCCAATTACAATAGACCCAGACCCACAGTCTCTGAAGATTGACTGTACAGT
    TCAACCCAGCCCTGTACTTCTCTTCCCTAGAATTTACATTACTGAGTAACTGAGGAAAGCTCTACAATAT
    CTGTTCTCTATAGTGGTCAACACCTCCAAACACAGGTTACCCATATTCATGCCTGCCTTCTGCTACACTT
    CTTGCCATAATGTAGACTACTTCAGCCTATTTTGTACTCCAGTTAACGAAACTCAAGACTAGCTGCATGT
    TAGTCCTTATTCTGAAATATTATGAACAGGTGACCTCCCATCATTCACCAATGCAATAATCATATTTAGG
    AATATGAGGTTTTATGAGATATAAGCACAAGGGAGAGAAAGTAAGAAAACTACATAGATATATAGACTGA
    CATAAATCAAGACTTGCATGAGCTAGTGCCCAAGTACCATGTCCCTAAGTGGCAAGGAGTATCTTTTGAG
    CCTAGTGAGATGAGGTACAAATCGGACTCTTACATCTTTTTAGATAAACATGTGAGATCAATGGACTAAA
    GGCGTGAGCTGGGCTTCCTTGCAATCCATTTTCCATACAAGATAACAATAGATCTGGCTCCACAGACACG
    ATGAGAATAGTCTTAATTAGTTCTTTAAGTAGAATGACTGATCACTAAGAGCCCAATTCCATACTAAATA
    CTCTTCTGGATTATGCACAGATAAAAATTGCACATAGGGCATGGGGCACTGATCTCCCTGCACTACATGA
    ATGGGGGCTCATTTACTAAATGTTCCCATGTTTCTTCCTAGTGCTGCACAGAGCAAATCCTACAACTTCC
    TGCTTGTCTACAATGTAAACTCCAGACAGTACCAGAAAATCATTCCTTATGTTCCTCTCCAGGTGCTTCA
    ACAAGCACAGTGCAAATTTCTGTCACCCTG
  • Molecule Role : Vaximmutor
  • Additional Molecule Role : Vaximmutor
  • Related Vaccine(s): Yersinia enterocolitica sodA mutant vaccine
IV. Vaccine Information
1. Y. enterocolititica Subunit V Antigen Protein Vaccine
a. Vaccine Ontology ID:
VO_0011503
b. Type:
Subunit vaccine
c. Status:
Research
d. Gene Engineering of LcrV
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
e. Adjuvant: complete Freunds adjuvant
f. Immunization Route
Subcutaneous injection
g. Mouse Response
  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were injected subcutaneously (s.c.) with 30 lg rVagHis in CFA and boostered with 30 lg rVagHis in ICFA four weeks later. Control mice were treated similarily with CFA or ICFA, but lacking rVagHis (Schmidt et al., 1999).
  • Challenge Protocol: Mice were challenged intraperitoneally (i.p.) with 0.5 ml bacterial suspension containing either 3x103 cells of Y. enterocolitica 0:8 strain NCTC10938 or 4x104 cells of Y. pseudotuberculosis strain YPlll/pIB102. Survival of mice was monitored over 2 months (Schmidt et al., 1999).
  • Efficacy: Mice actively immunized using a recombinant V antigen (rVagHis, encoded by lcrV gene) of Y. enterocolitica were completely protected against challenge with both, Y. enterocolitica 0:8 and Y. pseudotuberculosis serotype III (Schmidt et al., 1999).
2. Yersinia enterocolitica aroA mutant vaccine
a. Vaccine Ontology ID:
VO_0002935
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of aroA
  • Type: Gene mutation
  • Description: This aroA mutant is from Yersinia enterocolitica (Bowe et al., 1989).
  • Detailed Gene Information: Click here.
f. Immunization Route
Oral immunization
g. Mouse Response
  • Persistence: An aroA mutant is highly attenuated in mice (Bowe et al., 1989).
  • Efficacy: After 3 doses, an aroA mutant induces significant protection in mice from challenge with wild type Y. enterocolitica (Bowe et al., 1989).
3. Yersinia enterocolitica htrA mutant vaccine
a. Vaccine Ontology ID:
VO_0002936
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of htrA
  • Type: Gene mutation
  • Description: This htrA mutant is from Yersinia enterocolitica (Li et al., 1996).
  • Detailed Gene Information: Click here.
f. Immunization Route
Oral immunization
g. Mouse Response
  • Persistence: An htrA mutant is attenuated in mice (Li et al., 1996).
  • Efficacy: An htrA mutant provides partial protection in mice from challenge with wild type Y. enterocolitica (Li et al., 1996).
4. Yersinia enterocolitica ompR mutant vaccine
a. Vaccine Ontology ID:
VO_0002937
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of ompR
f. Immunization Route
Oral immunization
g. Mouse Response
  • Persistence: An ompR mutant is attenuated in mice (Dorrell et al., 1998).
  • Efficacy: An ompR mutant provided partial protection in mice from challenge with wild type Y. enterocolitica (Dorrell et al., 1998).
5. Yersinia enterocolitica sodA mutant vaccine
a. Vaccine Ontology ID:
VO_0002938
b. Type:
Live, attenuated vaccine
c. Status:
Research
d. Host Species as Laboratory Animal Model:
Mouse
e. Gene Engineering of sodA
  • Type: Gene mutation
  • Description: This sodA mutant is from Yersinia enterocolitica (Igwe et al., 1999).
  • Detailed Gene Information: Click here.
f. Immunization Route
Oral immunization
g. Mouse Response
  • Persistence: A sodA mutant is attenuated in mice (Igwe et al., 1999).
  • Efficacy: A single dose of a sodA mutant provided protection in mice from challenge with wild type Y. enterocolitica (Igwe et al., 1999).
  • Host Gene Response of Ifng (Interferon gamma)
    • Gene Response: Restimulated T cells from mice immunized with the mutant strains produced significant quantities of IFN-γ by day 8 after oral immunization compared to the control group of nonrestimulated T cells. However, the amounts of IFN-γ produced by T cells from mice immunized with the mutant strains were lower than those of mice immunized with the wild-type Y. enterocolitica strain (Igwe et al., 1999).
    • Detailed Gene Information: Click here.
  • Host Gene Response of IgG
    • Gene Response: Mice immunized with a sodA mutant elicited high titers of serum IgG antibodies. On day 23, WA-314 sodA elicited a 17-fold-higher titer of Yersinia-specific serum IgG antibody than WA irp1 (an irp1 mutant). Mice immunized with WA-314 sodA elicited a 10-fold-higher titer of serum IgG antibody than those given WA(pYVO8-A-2) (a YadA mutant) 90 days after the immunization. IgG levels from days 7 to 90 post-immunization were significantly greater than control serum obtained pre-immunization (Igwe et al., 1999).
    • Detailed Gene Information: Click here.
V. References
1. Bowe et al., 1989: Bowe F, O'Gaora P, Maskell D, Cafferkey M, Dougan G. Virulence, persistence, and immunogenicity of Yersinia enterocolitica O:8 aroA mutants. Infection and immunity. 1989; 57(10); 3234-3236. [PubMed: 2777382].
2. Dorrell et al., 1998: Dorrell N, Li SR, Everest PH, Dougan G, Wren BW. Construction and characterisation of a Yersinia enterocolitica O:8 ompR mutant. FEMS microbiology letters. 1998; 165(1); 145-151. [PubMed: 9711851].
3. Igwe et al., 1999: Igwe EI, Rüssmann H, Roggenkamp A, Noll A, Autenrieth IB, Heesemann J. Rational live oral carrier vaccine design by mutating virulence-associated genes of Yersinia enterocolitica. Infection and immunity. 1999; 67(10); 5500-5507. [PubMed: 10496939].
4. Li et al., 1996: Li SR, Dorrell N, Everest PH, Dougan G, Wren BW. Construction and characterization of a Yersinia enterocolitica O:8 high-temperature requirement (htrA) isogenic mutant. Infection and immunity. 1996; 64(6); 2088-2094. [PubMed: 8675311].
5. Schmidt et al., 1999: Schmidt A, Schaffelhofer S, Müller K, Röllinghoff M, Beuscher HU. Analysis of the Yersinia enterocolitica 0:8 V antigen for cross protectivity. Microbial pathogenesis. 1999; 26(4); 221-233. [PubMed: 10089162].
6. Wiki: Yersinia enterocolitica: Yersinia enterocolitica [http://en.wikipedia.org/wiki/Yersinia_enterocolitica]