Status
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Gene information
General information
TC002285 Gene

The sequence from the iB fragment is matched against the genes from the official gene set. The matche(s) is/are visualizied in a genome browser.

NW_015451937.1: 109176..166314
Sequence information
Transcripts / Proteins (1) Get mRNA sequence
Get CDS sequence
Get protein sequence
Ortholog information (from OrthoDB)

The information about the homolog genes in Drosophila is provided by OrthoDB http://www.orthodb.org/. The homologs are sorted according to their similarity score. For an orthology statement additional analysis are required.
The data basis for the orthologs is OrthoDB v9 containing OGS3 for Tribolium castaneum and 2015_04 (r6.07) for Drosophila melanogaster.

Closest fly homologs
    		TC002285
    Gene ontology

    GO terms for Tribolium

    • {{ goTerm.term }}
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      Status: {{ goTerm.status }}
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      Quotation: {{ goTerm.quotation }}
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    There are no GO terms for Tribolium at the moment. You can help the community by providing some GO terms for this gene.


    GO terms for the homologous Drosophila genes

    Assign a GO term to this Tribolium gene by filling in the fields. Repeat to add several GO terms. Search AmiGO for the correct GO ID. Use only the most specific term - use "graph views" to browse related terms ("child terms" are more specific; the more general "parent" terms will be automatically linked). Only information based on Tribolium data should be entered - do not define terms just based on Drosophila knowledge. We will review this information and submit the annotation to the Gene Ontology consortium.


    Gene
    {{ goGene }}
    The Tribolium gene the GO term is assigned to.
    GO ID *
    {{ blurIdResult }}
    The ID of the GO term you assign to the gene. Please enter only the ID of the GO term with proceeding 'GO:'. This information is mandatory.
    Evidence
    {{ blurEvidenceResult }}
    The evidence code describes with which method the function or location, expressed by the GO term, was show for this gene. Please refer to this page for a definition of the evidence code and a decision tree.
    Reference *
    {{ blurReferenceResult }}
    The reference where the function or location is described for the gene. Please enter a PubMed ID. This information is mandatory.
    Quotation
    If you paste here the relevant section of the reference it is for us a great help to review your annotation. The quotation may be also be displayed to the users of iBeetle-Base.
    Name
    You may enter your name. The contact information can help us to clarify any questions. If you agree, we may show your name on this page to honor your contribution.
    Email
    We will use your email address only for possible questions regarding this annotation. We will never show your address or give it away.
    Publish name
    If you have entered your name and agree by marking the checkbox. we might show your name on this page to honor your contribution.
      {{ unavailableText }}

    * : mandatory fields
    For help on how to submit larger datasets or non experimental data please contact us.
    iBeetle screen iB_03342

    Attention! iBeetle is a first pass screen. Hence, the documented phenotypes need to be confirmed by independent experiments using non-overlapping dsRNA fragments! Phenotypes with a penetrance > 50% are frequently reproduced. See Schmitt-Engel et al. 2015 for details on reproducibility.

    iB sequence
    Phenotype after pupal injection
    Usually 10 injected animals

    Pupal injection procedure

    Day 0: 10 female pupae of the pBA19 strain (muscle enhancer trap line) were injected with dsRNA.

    3 days post injection (dpi): Hatch control: Pupal and adult lethality as well as metamorphosis defects (molting, eclosion) were documented. For mating, 4 males of the black strain were added.

    9 dpi: First egg-lay was collected and incubated for cuticle analysis. Adult lethality and egg production (reduced/ no egg-lay) was documented.

    11 dpi: Second egg-lay was collected and incubated for embryonic muscle analysis. Adult lethality and egg production (reduced/ no egg-lay) were documented.

    Note: The adult morphology was not analyzed systematically at 3/9/11 dpi. Only obvious phenotypes, visible without magnification, have been annotated.

    13 dpi: Egg productivity and Ovary analysis
    The percentage of hatched larvae was documented and not hatched larvae/ eggs were embedded for cuticle analysis (15 dpi). In case of a reduction of egg production, 4 injected females were dissected to analyze the gross morphology of the ovaries.

    14 dpi: Analysis of embryonic musculature and early embryonic development
    Offspring of the injected females (hatched and not hatched larvae/ eggs) were analysed for embryonic lethality and muscle defects.

    15 dpi: Analysis of larval instar 1 cuticle
    Offspring of injected females were analysed and cuticle phenotypes were annotated.

    22 dpi: Stink gland analysis
    Documentation of defects in abdominal and thoracic stink glands (colour, size, content) of the injected femals.

    Terms used in the pupal injection procedure

    larval pantagmatic defects
    At least two tagmata (head, thorax, abdomen or terminus) show similar/ comparable defects.
    empty eggs
    Just empty shells are visible, no cuticle has been developed.
    strong defects
    L1 cuticle larvae which show severe defects. These strong defects are subdivided into three categories
    strongly fragmented (cuticle crumbs)
    No segments or appendages are identifiable, only residues of cuticle and bristles can be identified.
    cuticle remnants (with unidentifiable segments)
    Segments or parts of appendages are recognizable, but identity is not clear.
    cuticle remnants (with some identifiable segments)
    At least one segment or appendage is clearly regonizable.
    number of eggs on slide
    affected embryos usually (not always) do not hatch. Only the not hatched were used for cuticle analysis.
    For the embryonic muscle analysis the hatched as well as the not hatched were analysed.
    total number of affected eggs/embryos/larvae
    Summary of all different phenotypes/ phenotypic series which were annotated.
    inside-out
    The L1 larva shows a partial or complete inversion., e.g. bristles, appendages or parts of the abdominal segments are inverted into the interior of the cuticle.
    starved
    Dissected females show a strong resorption of fatbody predominately in the abdomen and the oogenesis is blocked. These are considered as eventually lethal phenotypes and the blocked oogenesis probably a secondary defect due to starvation.
    eclosion not fulfilled
    The emergence of the adult from the pupa stage is interrupted. This phenotype shows pupal as well as adult features.
    Please see the help page for more information
    Metamorphosis and survival

    Lethality 11 days after pupal injection: 50.0% (includes death as pupa, adult)

    eclosion not fulfilled (with pupal and adult features) - Number of animals showing the phenotype: 2 (3 dpi)
    Days post injection

    adult lethality - Number of animals showing the phenotype: 3 (9 dpi)
    Days post injection

    Analysis of embryonic musculature and early development
    number of eggs/embryos/larvae on slide: > 50 larval musculature pattern irregular - Penetrance (percentage of animals/eggs on slide): less than 30%

    affected eggs/embryos/larvae - Penetrance (percentage of animals/eggs on slide): less than 30%
    remarks: muscle pattern potentially obscured by segmentation defect,
    Analysis of larval stage 1 cuticle
    number of eggs/embryos/larvae on slide: < 20
    Phenotype after larval injection
    Usually 10 injected animals

    Larval injection procedure

    Day 0: 10 female L5-6 larvae of the D17Xhom strain (females express RFP in the eyes and in the CNS; pupae express GFP in the thorax) were injected with dsRNA.

    11 days post injection (dpi): Pupal morphology Documentation of larval/ pupal death and defects of metamorphosis (eclosion, delayed development). Screening for alterations of pupal head and appendages, pupal thorax, pupal thoracic musculature, pupal legs, pupal wings, pupal abdomen and pupal genital lobes.

    16 dpi: Adult morphology Documentation of larval/ pupal and adult death and defects of metamorphosis (eclosion, delayed development). Screening for alterations of adult head and appendages, adult thorax, adult elytra and hindwings, adult legs and cuticle properties. For mating 4 males of the black strain were added.

    19 dpi: Sieving and egg-lay Documentation of adult lethality and enduring metamorphosis defects.

    22 dpi: Ovary analysis (Fertility) In case of a reduction of egg production 4 females were dissected and the gross morphology of the ovaries were analysed.

    41 dpi: Fertility and stink gland analysis Documentation of defects in abdominal and thoracic stink glands development (colour, size, content) of the injected females. Check for fertility of injected larvae (no or decreased offspring).

    Terms used in the larval injection procedure

    pupal/ adult pantagmatic defects
    At least two tagmata (head, thorax, abdomen or terminus) show similar/ comparable defects.
    pupal molt not fulfilled
    The hatching from the larva to the pupa is interrupted. Either it dies as prepupa or the phenotype shows larval as well as pupal features.
    eclosion not fulfilled
    The emergence of the adult from the pupa stage is interrupted. This phenotype shows pupal as well as adult features.
    starved
    Dissected females show a strong resorption of fatbody predominately in the abdomen and the oogenesis is blocked. These are considered as eventually lethal phenotypes and the blocked oogenesis probably a secondary defect due to starvation.
    Metamorphosis and survival

    Lethalities 11 days after larval injection: % (includes death as larva, prepupa, pupa)
    Lethalities 22 days after larval injection: % (includes death as larva, prepupa, pupa, adult)

    iBeetle screen iB_06665

    Attention! iBeetle is a first pass screen. Hence, the documented phenotypes need to be confirmed by independent experiments using non-overlapping dsRNA fragments! Phenotypes with a penetrance > 50% are frequently reproduced. See Schmitt-Engel et al. 2015 for details on reproducibility.

    iB sequence
    Phenotype after pupal injection
    Usually 10 injected animals

    Pupal injection procedure

    Day 0: 10 female pupae of the pBA19 strain (muscle enhancer trap line) were injected with dsRNA.

    3 days post injection (dpi): Hatch control: Pupal and adult lethality as well as metamorphosis defects (molting, eclosion) were documented. For mating, 4 males of the black strain were added.

    9 dpi: First egg-lay was collected and incubated for cuticle analysis. Adult lethality and egg production (reduced/ no egg-lay) was documented.

    11 dpi: Second egg-lay was collected and incubated for embryonic muscle analysis. Adult lethality and egg production (reduced/ no egg-lay) were documented.

    Note: The adult morphology was not analyzed systematically at 3/9/11 dpi. Only obvious phenotypes, visible without magnification, have been annotated.

    13 dpi: Egg productivity and Ovary analysis
    The percentage of hatched larvae was documented and not hatched larvae/ eggs were embedded for cuticle analysis (15 dpi). In case of a reduction of egg production, 4 injected females were dissected to analyze the gross morphology of the ovaries.

    14 dpi: Analysis of embryonic musculature and early embryonic development
    Offspring of the injected females (hatched and not hatched larvae/ eggs) were analysed for embryonic lethality and muscle defects.

    15 dpi: Analysis of larval instar 1 cuticle
    Offspring of injected females were analysed and cuticle phenotypes were annotated.

    22 dpi: Stink gland analysis
    Documentation of defects in abdominal and thoracic stink glands (colour, size, content) of the injected femals.

    Terms used in the pupal injection procedure

    larval pantagmatic defects
    At least two tagmata (head, thorax, abdomen or terminus) show similar/ comparable defects.
    empty eggs
    Just empty shells are visible, no cuticle has been developed.
    strong defects
    L1 cuticle larvae which show severe defects. These strong defects are subdivided into three categories
    strongly fragmented (cuticle crumbs)
    No segments or appendages are identifiable, only residues of cuticle and bristles can be identified.
    cuticle remnants (with unidentifiable segments)
    Segments or parts of appendages are recognizable, but identity is not clear.
    cuticle remnants (with some identifiable segments)
    At least one segment or appendage is clearly regonizable.
    number of eggs on slide
    affected embryos usually (not always) do not hatch. Only the not hatched were used for cuticle analysis.
    For the embryonic muscle analysis the hatched as well as the not hatched were analysed.
    total number of affected eggs/embryos/larvae
    Summary of all different phenotypes/ phenotypic series which were annotated.
    inside-out
    The L1 larva shows a partial or complete inversion., e.g. bristles, appendages or parts of the abdominal segments are inverted into the interior of the cuticle.
    starved
    Dissected females show a strong resorption of fatbody predominately in the abdomen and the oogenesis is blocked. These are considered as eventually lethal phenotypes and the blocked oogenesis probably a secondary defect due to starvation.
    eclosion not fulfilled
    The emergence of the adult from the pupa stage is interrupted. This phenotype shows pupal as well as adult features.
    Please see the help page for more information
    Metamorphosis and survival

    Lethality 11 days after pupal injection: 50.0% (includes death as pupa, adult)

    eclosion not fulfilled (with pupal and adult features) - Number of animals showing the phenotype: 4 (3 dpi)
    Days post injection

    adult lethality - Number of animals showing the phenotype: 1 (9 dpi)
    Days post injection

    Analysis of embryonic musculature and early development
    low validity due to technical reasons - should be repeated: musculature not scorable,
    Analysis of larval stage 1 cuticle
    number of eggs/embryos/larvae on slide: < 20
    Phenotype after larval injection
    Usually 10 injected animals

    Larval injection procedure

    Day 0: 10 female L5-6 larvae of the D17Xhom strain (females express RFP in the eyes and in the CNS; pupae express GFP in the thorax) were injected with dsRNA.

    11 days post injection (dpi): Pupal morphology Documentation of larval/ pupal death and defects of metamorphosis (eclosion, delayed development). Screening for alterations of pupal head and appendages, pupal thorax, pupal thoracic musculature, pupal legs, pupal wings, pupal abdomen and pupal genital lobes.

    16 dpi: Adult morphology Documentation of larval/ pupal and adult death and defects of metamorphosis (eclosion, delayed development). Screening for alterations of adult head and appendages, adult thorax, adult elytra and hindwings, adult legs and cuticle properties. For mating 4 males of the black strain were added.

    19 dpi: Sieving and egg-lay Documentation of adult lethality and enduring metamorphosis defects.

    22 dpi: Ovary analysis (Fertility) In case of a reduction of egg production 4 females were dissected and the gross morphology of the ovaries were analysed.

    41 dpi: Fertility and stink gland analysis Documentation of defects in abdominal and thoracic stink glands development (colour, size, content) of the injected females. Check for fertility of injected larvae (no or decreased offspring).

    Terms used in the larval injection procedure

    pupal/ adult pantagmatic defects
    At least two tagmata (head, thorax, abdomen or terminus) show similar/ comparable defects.
    pupal molt not fulfilled
    The hatching from the larva to the pupa is interrupted. Either it dies as prepupa or the phenotype shows larval as well as pupal features.
    eclosion not fulfilled
    The emergence of the adult from the pupa stage is interrupted. This phenotype shows pupal as well as adult features.
    starved
    Dissected females show a strong resorption of fatbody predominately in the abdomen and the oogenesis is blocked. These are considered as eventually lethal phenotypes and the blocked oogenesis probably a secondary defect due to starvation.
    Metamorphosis and survival

    Lethalities 11 days after larval injection: % (includes death as larva, prepupa, pupa)
    Lethalities 22 days after larval injection: % (includes death as larva, prepupa, pupa, adult)

    RNAi sequence
    Primers
    Left: Right:
    Protein sequence
    • >TC002285 RA
      MLLLLVIVP VVICVSDNF LKMFEGQKP PVDPCYDED 
RPRRCIPDF VNAAFGIPV KASSTCGLH SPVQFCEVS 
EPEGNSQCY ICDDKLPKN RFPASHLTD LNNPNNVTC 
WRSDPLLPV TSINAAPDN VTLVLSLGK KYELTYVSL 
QFCPNTPKP DSIAIYKSM DYGKTWQAF QFYSTQCRR 
VYGRPNKAT ITKVNEQEA RCTDAHRYT GGDNQGFGQ 
SSRIAFSTL EGRPSALDF DNSPVLQDW ITATDIKII 
FNRLYMPLE DASSENFDT LVDELKNKQ TDDDLNFTK 
EPVVQLVNE MQPLDTNDP KTPTSVELT SNGVAGGYN 
QITHQYAVA DFAVGGRCK CNGHASRCI TGRDGQLAC 
ECKHNTAGK DCERCKPFH FDRPWGRAT ARDANECKA 
CECNQHARR CRFNMELYK LSGRVSGGV CLKCRHYTA 
GRHCHYCRE GFYRDPTKQ ITHRKACKP CDCHPIGSS 
GRTCNQATG QCPCKDGVV GTTCNRCAK GYQQSRSHI 
APCIKIPVV QIMATEEED NDYGDEDPD QPAAGVQCG 
KCKSSTKRL NLNKYCKRD YAIMARVLS RMEGNEDQH 
TKGWTRFMV NIEFIYKKS RDSQIRKGT MPMVVPTAD 
LACKCPKLK PSKSYLFLG REKDDSPGG VLTGSLGVT 
ERSIVIEWR DEWDQRMRR FRRRARKCK
    CDS sequence
    • >TC002285 RA
      atgttattg ttactcgta attgtgccc gttgtgatt 
tgtgtttct gataacttt ctcaagatg ttcgagggg 
caaaaaccc ccggttgac ccctgctac gacgaagac 
cgcccccgt cgttgcatt ccagacttt gtaaatgca 
gcgttcggt atcccagta aaagcgtct tctacctgc 
ggtcttcat tcacctgtg caattttgc gaagtttcg 
gaaccagag ggcaattcc cagtgctac atatgcgac 
gacaaattg ccaaagaat cgatttcca gcatctcac 
ctcacagat cttaacaat cccaacaac gtgacttgt 
tggaggtct gacccgctg cttccagtg acttccatt 
aatgctgca ccagataac gtaacgttg gttctcagt 
ttaggaaag aagtacgag ctgacgtat gtaagcctg 
cagttttgc cccaacaca cctaagccc gattcaatc 
gcaatctac aaaagcatg gactacggg aagacatgg 
caagcgttt cagttctat tcgactcag tgtcgcaga 
gtttacggc agaccaaac aaagcaacc attactaaa 
gtcaatgaa caggaggca cgatgtact gatgctcat 
cggtatacg ggaggtgat aatcaaggt ttcggacag 
tcgtccaga atagcgttc agtacactt gagggccgc 
ccaagtgct ttggatttc gacaactcg ccggtgctc 
caagactgg atcaccgcc accgatatt aaaatcatt 
tttaatcgc ctttacatg cctctagag gatgcgtct 
tccgaaaac ttcgataca ctcgttgac gaattaaaa 
aacaaacaa acagacgat gatcttaat tttaccaaa 
gaaccggtc gtccagttg gtgaacgaa atgcaaccc 
ttagacacg aatgatccc aaaacaccc acatcagtg 
gaattgact tcaaatggg gtagccggt ggttacaac 
caaattact caccagtat gccgtcgcc gattttgcc 
gtcggagga agatgcaaa tgtaatgga catgcaagt 
cgctgcata acaggtaga gatggacaa ttagcatgt 
gagtgtaaa cataatacg gctggaaag gattgcgaa 
agatgtaaa ccattccat tttgataga ccttggggc 
agagccact gctcgggac gcaaatgaa tgcaaagct 
tgtgaatgc aaccaacat gctcgtcgt tgtcgattc 
aacatggaa ctttataaa ctgtccgga agagtttcc 
ggtggcgtt tgtttaaaa tgtcgacac tatacagca 
ggaagacat tgtcattat tgcagagaa ggtttttat 
agagatcct acaaaacaa attactcat cgtaaagca 
tgtaaacct tgtgactgc caccctatt ggatcttcc 
ggtagaacc tgcaatcaa gccacagga caatgtcca 
tgtaaagat ggtgtggtt gggactacc tgcaataga 
tgtgcaaaa ggttaccaa caaagccga tcccatatt 
gcaccgtgc ataaaaatt cctgtagtg caaataatg 
gctaccgaa gaagaagac aatgattat ggagacgaa 
gatccagat caacctgca gctggagtt caatgtgga 
aaatgcaaa tccagcacg aagagatta aacttgaat 
aaatattgt aaaagagac tatgctatc atggcgaga 
gtcttgtcg cgaatggaa ggtaatgaa gaccaacat 
acaaaagga tggacgcga tttatggtg aatatagaa 
ttcatctac aaaaaatca agggattct caaatacgt 
aaaggcact atgcctatg gtcgtgcca acagcagat 
ctggcttgt aaatgtcct aaactcaaa cctagcaag 
tcctacctg tttttagga agagagaaa gacgattct 
cccggagga gttcttacg ggtagttta ggtgtcaca 
gaaagatca attgtcatt gaatggaga gatgagtgg 
gatcaaagg atgcgaaga tttcgtcga agagctcgc 
aaatgcaag taa
    mRNA sequence
    • >TC002285 RA
      acgcatttc gcagtaaat ttaaattgc aataatttg 
atacgaggt cggagcaga gcagacagc ggaccgcca 
gttattcaa cggcagtcg gagtgaggg aagtgttcc 
tcgaattgg acacatcgc acgcggact aataaatca 
aaactatcg gcaacgctg ttttcgaaa tcgatgtgt 
gaaaaacgt gtgtctaaa aacatgaaa tcgtttgat 
tgctaagtt gtgcgattc attcataac atgtgcagt 
gcagtgaat atgttattg ttactcgta attgtgccc 
gttgtgatt tgtgtttct gataacttt ctcaagatg 
ttcgagggg caaaaaccc ccggttgac ccctgctac 
gacgaagac cgcccccgt cgttgcatt ccagacttt 
gtaaatgca gcgttcggt atcccagta aaagcgtct 
tctacctgc ggtcttcat tcacctgtg caattttgc 
gaagtttcg gaaccagag ggcaattcc cagtgctac 
atatgcgac gacaaattg ccaaagaat cgatttcca 
gcatctcac ctcacagat cttaacaat cccaacaac 
gtgacttgt tggaggtct gacccgctg cttccagtg 
acttccatt aatgctgca ccagataac gtaacgttg 
gttctcagt ttaggaaag aagtacgag ctgacgtat 
gtaagcctg cagttttgc cccaacaca cctaagccc 
gattcaatc gcaatctac aaaagcatg gactacggg 
aagacatgg caagcgttt cagttctat tcgactcag 
tgtcgcaga gtttacggc agaccaaac aaagcaacc 
attactaaa gtcaatgaa caggaggca cgatgtact 
gatgctcat cggtatacg ggaggtgat aatcaaggt 
ttcggacag tcgtccaga atagcgttc agtacactt 
gagggccgc ccaagtgct ttggatttc gacaactcg 
ccggtgctc caagactgg atcaccgcc accgatatt 
aaaatcatt tttaatcgc ctttacatg cctctagag 
gatgcgtct tccgaaaac ttcgataca ctcgttgac 
gaattaaaa aacaaacaa acagacgat gatcttaat 
tttaccaaa gaaccggtc gtccagttg gtgaacgaa 
atgcaaccc ttagacacg aatgatccc aaaacaccc 
acatcagtg gaattgact tcaaatggg gtagccggt 
ggttacaac caaattact caccagtat gccgtcgcc 
gattttgcc gtcggagga agatgcaaa tgtaatgga 
catgcaagt cgctgcata acaggtaga gatggacaa 
ttagcatgt gagtgtaaa cataatacg gctggaaag 
gattgcgaa agatgtaaa ccattccat tttgataga 
ccttggggc agagccact gctcgggac gcaaatgaa 
tgcaaagct tgtgaatgc aaccaacat gctcgtcgt 
tgtcgattc aacatggaa ctttataaa ctgtccgga 
agagtttcc ggtggcgtt tgtttaaaa tgtcgacac 
tatacagca ggaagacat tgtcattat tgcagagaa 
ggtttttat agagatcct acaaaacaa attactcat 
cgtaaagca tgtaaacct tgtgactgc caccctatt 
ggatcttcc ggtagaacc tgcaatcaa gccacagga 
caatgtcca tgtaaagat ggtgtggtt gggactacc 
tgcaataga tgtgcaaaa ggttaccaa caaagccga 
tcccatatt gcaccgtgc ataaaaatt cctgtagtg 
caaataatg gctaccgaa gaagaagac aatgattat 
ggagacgaa gatccagat caacctgca gctggagtt 
caatgtgga aaatgcaaa tccagcacg aagagatta 
aacttgaat aaatattgt aaaagagac tatgctatc 
atggcgaga gtcttgtcg cgaatggaa ggtaatgaa 
gaccaacat acaaaagga tggacgcga tttatggtg 
aatatagaa ttcatctac aaaaaatca agggattct 
caaatacgt aaaggcact atgcctatg gtcgtgcca 
acagcagat ctggcttgt aaatgtcct aaactcaaa 
cctagcaag tcctacctg tttttagga agagagaaa 
gacgattct cccggagga gttcttacg ggtagttta 
ggtgtcaca gaaagatca attgtcatt gaatggaga 
gatgagtgg gatcaaagg atgcgaaga tttcgtcga 
agagctcgc aaatgcaag taaattaac tcgtacgtt 
aatgaaagt tactaaatt gttccatac attttgtaa 
aagatgcta gcagtgtca ctgtgattt aattttaac 
gtatctgtt taagagact taaagcatt ttaagggcg 
cgtttaaaa gtacactac ctcatttta tcattatca 
gtttttcct ttagagaat aaagaaatc aaaatatt
    The data is licensed under a Creative Commons Attribution 3.0 Unported License. (CC-BY) CC-BY