[2]bioinformatica componente genético de epilepsia en lóbulo temporal

7/31/2019 [2]Bioinformatica Componente gentico de Epilepsia en lbulo temporal

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Oscar Leonardo Mosquera Dussan.

Ingeniero Electrnico.

Universidad de la Sabana.

Facultad de Ingeniera.

Doctorado en Biociencias.

Componente gentico de Epilepsia en lbulo temporal

Introduccin

Estudios recientes reportan mutacin de la protena leucine-rich glioma-inactivated-1

(LGI1), como causa de epilepsia parcial en humanos [1-3], anormalidad en el gen LGI1asociado a la protena es responsable de epilepsia autonmica dominante de lbulo

temporal [4-6]. Tambin se presenta un rol del gen LGI1 en epilepsias autoinmunes [7].

En la actualidad, poco se sabe sobre el patrn de expresin temporal y espacial del gen

LGI1 durante la embriognesis normal, un reciente estudio con un ratn transgnico

implican que Lgi1 puede tener un papel en el establecimiento de la arquitectura normal

del cerebro y funciones neuronales durante el desarrollo cerebral lo que sugiere que

pueden estar implicados en la neurognesis y la plasticidad neuronal, que se define ms

especficamente en el animal adulto [8]. Otro estudio en animales muestra que el

truncamiento del gene LGI2 (homologo al gen LGI1 en humanos) muestra una remisin de

epilepsia focal en perros [9]; estudios sugieren que ambos genes presentan una gran

similitud en los mecanismos moleculares de la patognesis [10].

En el presente trabajo se realiza un estudio bioinformtico al gen LGI1, se estudian las

secuencias de ADN, ARNm, y la secuencia de aminocidos que forman la protena leucine-

rich glioma-inactivated-1.


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En ncbi se puede apreciar la informacin del gen LGI1 asociado a epilepsia de lbulo

temporal.

EL gen se encuentra ubicado en el cromosoma 10 y la presente secuencia no tiene

splicing alternativo.

La secuencia del gen en formato FASTA es la siguiente,

>gi|224589801:95517566-95557916 Homo sapiens chromosome 10, GRCh37.p5 Primary Assembly

GAAAGCAGAAAGCTGTTTATTTTCTGTGACATCACTTCACTTTGCCTTCGAAGGCTGGTCTGTGCTCAGT

GTTTTCGTGGTGATGCAAGTCGGCTCTCTCCTCCAGCAGTTGGATCCCTCCCATCTCACAGTACCTCACA

GGTCTCTTCCCCCGAGCAGTGCATTGCTGGAGCGAGGAGAAGCTCACGAATCAGCTGCAGGTCTCTGTTT

TGAAAAAGCAGAGATACAGAGGCAGAGGAAAAGGGTGGACTCCTATGTGACCTGTTCTTAGAGCAAGACA

ATCACCATCTGAATTCCAGAAGCCCTGTTCATGGTTGGGGATATTTTCTCGACTGCATGGAATCAGAAAGAAGCAAAAGGATGGGAAATGCCTGCATTCCCCTGAAAAGAATTGCTTATTTCCTATGTCTCTTATCTGCG

CTTTTGCTGACTGAGGGGAAGAAACCAGCGAAGCCAAAATGCCCTGCCGTGTGTACTTGTACCAAAGATA

ATGCTTTATGTGAGAATGCCAGATCCATTCCACGCACCGTTCCTCCTGATGTTATCTCATTGTAAGGCCC

GTAAGCATTTTGATATCTAATTTACGATTTAAAAATTCCAGCCGGTGGATTTGGGGCTTTGCATGTATTT

GTAGAAGGGCATGGAGAGAGAGATTCCTCTTGCATGCTTGGCCATTTGACAGTGCTAACATTTGCTGCAT

TTAGAATTTTTGATTTTTTTAGCTGCTACTGAACATGCTTAGATACCCCCAGCCCTGAACATTATCATGA

GAAACCTGTAGCCGATTCATTTCTCTTACTTCATCTGGGAAGGAATAGTATCGTACTTCATAAAATAGTG

TCAAAATAGTCACTGTTATGCTAAACCGGATTAACATAAGGTTTGTTCTGTGTGTGTGTGTCTCTTTGTG

TGTGTCTGTTTGTTTGTTTTCTCTTTTTTGTTTTCTTTCAGATCCTTTGTGAGATCTGGTTTTACTGAAA

TCTCAGAAGGGAGTTTTTTATTCACGCCATCGCTGCAGCTCTTGTGAGAAATATTTATATCATGACTATT


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TTTAATATGGCATATATTTGGATAAGCCTTCTAGTAAAATGATCTCAATATTAATTTTGTCAAATGTGAT

TCTATTTCTGAGAAAACAGAATATCCGTAAAGTGAGAGGTAGATGGGTTTGTTTGCGACTTCACACCAAC

AGTGCAGGTTGATTCTTACAATGGTAAATCTGTTAACCTGTCATGCTGTCTACTTTAATGGCTATTTATG

AAGTTGTTGGAATCTTGCAACAATGATCCCAATTCCATTCCACTATTTTACTTTCATTTTTAACTTGGGA

ACTTGGGTTCTTTTGCCCTGGAGTTTTTGAATTAGTCAATACAGAACCCAGCATAACATATGCGCTCAAG

ATGTTGTCTCCGGGGATCTGGGGCAGGCTGCTACTCTGTATGATTTACCATGTGGGGAAAAAAAACACCT

CAGCTCTTTCTAGGTAATTCCTTAAAATGTTAATTCTCAAGAGACTGTTTTTTAATCTCATCTAATTTAT

AACTAGTTCCATTACAAGGAGGGAAAGAAAATATTAATATAGGATAGTGCAAAGGATTACTCTCTGCTAT

ATGTTTTGAGTTGGCCACAAGGGAACCACATACTCAGTCTATGCCTGAAAATATTCAAAAAAATAATATT

TGACTAAGAAATCAGATCTGTTCACAGGCATAATGGAACACATAAAATTTGTTCTGATGTGTAATGTTTG

GCAATTGGAGTCCTAGTCCTTACAGCGGTATCACATGGGGGTCAAGAGGTCTCCCAGGACTCAGGTATCA

GGTCGCAGACTTGGTTTGTAGCTGGACGGATATGGGCAGAATTAGACAATTGTGGATCAGCTGAGTCTTG

GCTATCTTAACTGCATGATTCAGGACCCAGGCCTTTCACTTGTTTGTTTTTTATTTTTTTATTTTCTTGC

CTTACTTGGCCATTTTGGCTGTTTGAAGTTACATACACAGAGGCAAACAGCATGGAGTGGACGTTGGAGA

GACAAGTGTTTAAACCTCACCCTGCCACTCATAGAACCTAAACATGTAGTCTTGTGCAGATTAGTATATC

TCACTAAGCCTCAGTCTTCTTATCTTTAAAATGGAAGTGAGAACACATACTTCCAAGGTTTAAGTAGATA

AAACACTTGGCATAGGGTGTGCCAAATGCTTACACATTTATAAATGGTAGGGTTTAAAAATTTTATATCA

AGCTAAAAAGCTAAAAGTCACTCATCTATTGTTTTGTGTATATGAAATTCCTAAACTGGTTTGACTGTTT

CATTGGATTCACAAACTTGATCAGTTGTTTTGACATTATGTAATGATGTTGGCTAATGCCCTTCTACTGG

CTGATGTCTTCAAATGATTAGCAATTGACTAGATATTCCTAAGGGGTTTATCTGTTTGATTGATGGCTAG

TGGTGTGACTGGGGGAAGTGTTAGTTAGCACATCAAACAAATCCAAAAAAGATAGATTCTTTCCCACAGA

AAGGGGCAGAGTCTCTAATGCTGGGATCCTTCCATAGGATAAGAATTTGCTGTCTCTGAGAAAGTGATAA

ATTGTGTTTCTGGTCCTCACTTGTTAAATGAATAAATAGCTCTTTTAAAAAGCATCCTTTTGATATGCTA

AGGCACCTCCCTTCCCCTAGGAAGTTACATAGATCTAGTTACATAGATCAGTCCTTAAAATTCCAGGAGTAGTGTCAGTAGACACTAGATGGACATTAGCTGTGGCACAGAAAGCCTGGAGTGATTAACCTAATCAATTA

CCACATCTCCACTTTGTTTTTGTTGGGTGGACCCAGTCACGGCAAGCACAGATGCTGGACAATGTTATAG

AAATAGTTACCGGCTGCTGCAGGGTAATGTGATTTCACGTATTTAGAATCACAGAGGGAAGCCAAGGGAC

TGGTTTTTAAATAGCCCAACCGAGTGTGTGCCATGCCCGTGCCCCATGCTCCGAGTTCCTATGGAACATT

CCAGCCTTTATTTCTAAAAGCAGTTCAGGTTTCAGAAATAACAAAAGGCGAGTAATTCTCTCCCAGTGTG

TTCTCGGTTAACTCAGATTGGCTAACCTCAACATGGTAGACTTGTGCCAGAGCTGAACTTATGCAAAATT

GTCAGGGGCCAAAGTTTGTCCCTAATCTCCAGGACCCTGTGCCTGAAGACTCTGCTCTCCATCCTTCTTG

CCCAATATTCTCTGCTTCCGCCTATCCTCAGGAAAAGGTCTAATAAACTCATGTGCGGTGTGTAGGAAAT

ATATGAGAAGGCTCTGAATATGAACTATGAAACGATCATAACAATTGTGGGAATGCATGGATCCCACAGA

GAAAGATCTCTTCTGTGAGACAGGGCTGTCCAGTGCCCTGAAAACCCCATATGGGCTGCCAATCCCCCTT

TGGAACATGAAGACCAATGGCATTGGACCACCAGATTAGGCCTAGATCACACAAGCCATTGAGGTTTGCA

ATGAATTCCAACAGCATTTGTGATTGTGAATTGCCACACTCACCCATCATACACTGTGAAGAGATAAATT

TCAGAATCAATTCGGCTTGATTGACGTAGGAAGACAGTTCGTTGGTTTCTTGCTTTATTGTTGGGAAGGG

TTAAAGCAAATGTCCTATTTCCATCATCCACCCTAAAAATCTGATAATGTCAGTATGCCCCCAGATGCTT

TTTCAGAGCTTCTGAAAAAGCTATGATGAGAAGTACTTGTTGAAATGTCAGTCTGGGGTACTGAGGAAAATAGACATGGTATCTGAAGTTACATGCAGTGTTTGGGAAAAGATCCTGGTAGGCCATGGCTGGCAGTTTGT

GTTGGAGAACAAGAAAAACAAAAACCCACATTCCGTAGAGAAGAGAGAGAAAGAATAAAATTATTCAATA

AAAATTCATTAGATTAGTTGTAATATACATTTTTTAAAAATCTCATTTATGGGTTTAAACATAACAATAA

AAACCTTTCCCAAGCAAATGCAATTTCATTCATGTTTTACATAGGGCCAGTTTCGAAACATAACCAATGA

CAACGATTATGCGTTCTAGCTTGCTTTTAGTGATAGAAAGTGGTACTTTTAGTGAATGCAGTTTAGGGAA

ATGTGTTTTCACACATTACAGCCCTGTTCCTTCTCAACTACAGACTGAAGTCCCCAATGATATGGGCTCA

TGATGGAAGTGAAATTCAAATTTAAGAGGACAAAATGTGGCCACTTCGCCACCCACTTATAACATATTTT

AATTATAAACCCCTGTAATTCCCGAGAGTGTTCTATTTTCAGGGAGTGATTTCCAGGGTAGTTTTAGTAT

CATGCTCAAATAAAACAACACAAAACAAAAACACTGCACGTAAGAATCCGACATGACCAGAAAAAATTTC

TTAGTATTCCAATTGGATGTGGTCTTGTTTGAAAGACAGAATTGATCTTTCAGGGTCAAAGGAGGGGAAT

AGCGTTATTTTAAAAATTAATCCACAATCAACACATAAATACCTGATCCATAAGAAATTAAAAACTAAAA

ACAAATGGAAAAGCAAAAGGCATGAACAAAAGAAGGAATAAGTCCATCCTTACTAAGGCTTTATCATTTA

GTCCTTCAAAATATGATCTGTCCAGGAAAAAATATCCATGGCCTCCTTTACCTTTAAAGCAATTGCTACC

TTTTTCTATTCCTCCTTATATTAGAAGCCTACAATTTAGCAGTCTTCAATGACCACTCAAGCCAAACCTA

TCAGCCAAGGGTGTTTTTGGAGGAATTATTAGCTGGTTATAGGTGAGCACGTTTTGGTTTGTATCCAGCT

GATGCCCCCATGATGGACCAAAAAGCAAAAATTTCAGTCATCTAGGCTGTTTTGTCTACAGTTTGCCCAA

TGATCCATAGATCTAATCTTTAACTTTTTAATTAATTACTTCTTTTTTGTTTTTACTTTCTTAAAAATAA

TTTTAAATTTTATTTTAGATTCGAGGGTCCATGTACAGGTTTGTTACTTGAAGTGAATTAATTCTCGTAA

CTGCACAAACTAGCACTCACCACAATTGTTTTCTCTGAAAGTGTATTTCATCCTTTCAGTTATTCAGGCA

AGAAACTTCAGAGTTACCTGACCCCTCTCTTTCACTCTCCACTTCCACCTGGACAAGCATCCTGTCCGAC

AGCATGAGAATCTGCCTCCTCCTCTTCACCACAGCACCACTGCTTTCACTGAGGCTGCATTTCATTCACT

GTTTCACAGGCTGTGGCAGGAGCCTCCACGCCTCACTGTCTGCTTTCAGTTCCCATCTGACCCATCTCCA

TTAGCGCTGCCTTTCCTGAGACACAGCTCTCCGTGCTTTCATGACTCCCTAGAAACAGAGAAAGTCCAGA

CACCTGAGCTGGCATCCATAGTGTTTGGCCCTTTCTATTTGTCCAAGGTTATCACTCACATCATTGACTC

TACACACACAGACACACACACACACACAGACACACACACACACACGTGCCCAAACAAGTTCTGCAGGATC

TCATTCTATGACCTCTGTTGATTCTCAAATTCTCTAGACTTTACTGATGTCTGGCACTGTGTGCCATTTG


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CTAGAGTTATGGTGCTTGTATCTGCCTTGTGTCTTTCATGGAGGATCACCAATAAACTGTGGTCCCAGAG

AAAAACCCAGACATGTTTTCCCATGTATTTGTTGAATCCAGTTTATGTTTCCATCGATTTTGTGCTGAAG

ACTCCTGTGTTACTCTCAGCAGATAATGCTGGTCATGTTCACACTCTTTCTGATGTTTGGTGCACCCTAT

CTGAATTCACGTGGACTAATAGTGTGGAGGTCTGGGAAGTGAGCCGAACTAAAAAAACTCGAGGAGATAT

TTGCTCATGAAGTTGTGAATTCAAACTTCCTCAGCAGAGATTTCCAGCATACCAGATTTCAAAGGCAAAG

CATCTAAGCCTTTCCTTAGACCCACCGCTCGAATCTCTTGTGTCCCACGCTGACTTCACATTTGGTCTCC

TTGGTTTTTAGTCAGACTGCAGAGGCCGACTAGTCTGTCCTGGGAAGGGTAAGATGCTCCTTTATCCAGC

CTGACCGGACATCCAGAGGGAAATGTTAGTTAAGCATTATTAATATGAAAAGAAAAATCAATAACACAAA

GATAATTTCCTTTTTGATTTAAGTACTGCTTAGCCAAAATAAGTATTTATTTATTGTATAGTTGCAAGCA

GCAACAAAATGAAAACAAAAGCCTCCCATTTTAGCAGACATGTTTTGAGGCTCTACTGGGTAGCAGGTAC

AATGTTGGGCTTTGTGAAGGACACAAAGATGAGTGACACGCTGTCACTTTTCACCCTGATATGGCAGCTC

CAAGCTGGTAGTGATTCTTGATATGGTAAATTATACTTTGCCTGTATTTGAATGCATTAGTTTCATTTAA

AAAATTATTTTTATGTAAGTAGAGATGAGGTCTTGCTATGTTGCCCACGCTGGTCTCGAACTCCTGGCCT

CAAACAATCCTCCCACCTCACCCTTCCAAAGTGCTGGGATTATGGGTATGTGCCTGGCCTCCTTAAATGT

ATTATAAGGTAGTCTTGATAAGCATTCTCATTTTGTTCAAAATGAGATTCAGTTGATTAGTGATGATGGT

GATGCTTGCTGGTTGTTGATCCTGTGGCTAATACGGGCTACAGAATGTCTGCAAGGGCTTTACAGCATCA

GCTGTAATATCAAAACAGCTGACCCTGGTGAGCTGGCAATGAGGCAGACAACACAGACTTGTGGGCAGAT

AAGCATGGGTTCAAATCCCCACTCTGCTTCTTCCTAGTTGTATGATTTGGGGCAAGCTTAATCAAGTCTT

GATATCTATATCTACAAAATGAGGAAGAACCGTAGTACCTATTGCACAGAATTACAGTAAGGATTAAGTA

AAACAATGCATGAAAAATGCTTTGCAAGGTTCCTGTAACTCAATACACATTAGCTTTATTACAGTATCTG

AAAATCACTTTAATTGGAACTACCATAACATCAGATTAGTGTCTGATTGTATAATCTGGGTTTGCCGATA

ATCTCAGCTTTAAACATTTTGTGGTTCTACACACAGTTCCCCAGCAGAACTTGCTGAGAAATCTTTTCTT

TAAATACTTCTTACAGGAAACATGAACTATTTACCTTTCAAAAAAAAGTCATAACCCTCTCCTTTCTTCC

TCATGAATAAAATGACTGGCACCACGTTTTGTAAAACATGCCAGATTTTGTTTAAATAATTAATATTGGCAGTCTTCAGATGAGTGGTTCTATGGTAGCATAGAAAGAGGCCTAAACTAGAAATCAGGAAACATGGGTTT

GAAACTCAGTTTGGCCACTATTGGGCTGCGTGATCCAATAGTTTGGGTAGGTCACAAAACTACCTAATAG

TTTGGGTAGGTCACAAAATATCACTGGACCTCAGCTTTTATTGCATAAAATATTAGAGGTAGATTAAACT

GTGGTTCTGAAACTCAAATGCTAGTGGGGTTTGGGGCGGTAAGACCAATGAAGGAAGCAGTTGAGTATAA

GACAATAAGGAGTAGTGGTGACTGAGGTAAACCAGAGAAGACATGTCTTACCTAAAAATCCTCTGCTCCA

ACTGACTATTGCTGATGGGATTGTGGTACATGCACATGGAGCCCTATCTTCCTCATTTTTAGGGGAAGGT

GGAATTCTGGAAGTAGATTTTTAAACAGGATAAAGACCAAACAAATATAAGTTGGCATTTTGAGACCCTT

GCATTCAATTACATCTAAGGTCTCCTCCTATCTTAAAATTCTGTTGTATTCTACAAACAGTTACGTTAAT

ATAATATAGAAATGGCATGGTTAAAGAAATGGACAACGATGGCTTGGCGCGGTGGCTCACGCCTGTAATC

CCAGCACTTTGGGAGGCCGAGGAGGGTAGATCACGAGGTCAGGAGATGGAGAACATCCTGGCTAATACGG

TGAAACCCCGTCTCTACTAAAAATACACAAAATTAGCCATGCGTGGTGGCGGGCGCCTGTAGTCCCAGCT

ACTCGGGAGGCTGAGGCAGGAGAATGGCGTGAACCCAGGAGGCGGAGCTTGCAGTGAGCCGAGATCGCGC

CACTGCACTCCAGCCTGGGCGACAGAGTAAGCCTCCGTCTCAAAAAAAAAAAAAAAAAAAAGAAATGGAC

AAAGATTATTGAATCAGTTCTAACAAACCAATACATTAGGTTGTTCATTGAAAGAAACTCATAATATGAA

ACTGGCTGTTATAAGGTTATTAATACAATAATTGTAGTTCCCAATCTCCCAAACAGGTCCAAAGGGACCTTACCAGGCTCTCCCTGTGGTGGTTGATGATAAAATGATGTTTCAGTATCCCTCTCATGGAGCAAGGATTG

GAAAAAAATTGTTAGGCCCATTTTTATATAGCAAGATGGCAGGTGCTTGCATGTGTAAAATGTGATCAAA

AGGCAATAAATCTTTAAAAATACAAACTAGAATGTATACATACAAATAACTCTTGACTTCACAGAGGGCC

ATAGATTTTGCCCAACTGTGCTTCCATGGCTAAAGATTTCTGGACCCTCCTTTGAGAATTGTCTTCATTG

CCAGTTTACAAGCCACGCAATAAAACCAGGCAAGGTTTTATTAGAGACATTAGTTATTTTTGTATTGCTT

GGTGCTAAGCATTTTATAGATCTCTTTTTTTTTTGAGACGGAGTCTCGCTCTGTCCCCCAGGCTGGAGTG

CAGTGGCGCGATCTCGGCTCACTGCAAGCTCCGCCTCCCGGGTTCACGCCATTCTCCTGCCTCAGCCTCC

CGAGTAGCTGGGACTACAGGCGCCCGCCACCACGCCCGGCTAATTTTTTTGTATTTTTTTAGTAGAGACG

GGGTTTCACCGTGTTAGCCAGGATGGTCTCGATTTACTGACCTCGTGATCCTCCCGCCTCGGCCTCCCGA

AGTGCTGGGATTACAGGCGTGAGCCACCACGCCCGGCCTATAGATCTCATTTTTAATGTCATCATCATGG

TAACCTTTTGAGGTAGATATAATTATCTCCATTTTGCAAATGAAGCGCTGAGTCCTAAAAGATAACCTCC

TCAATGTCACGCCCCTATTAAGTAGCAGAGTTGGAGTTTAAACCCATGTCCTCACTTTTAACCACTTCTG

TCTACTTCCTCCTGAACATGAATCATCATGCTTCACTTTGCATAGTTTTGTTCCCAAAATCAAATCCCCT

CTCAAAGGGTCAACCTTTGCCATTAACAAGAGTTTTCAGGAGAATGTGCCCTAATTCCTGGAGACAATGA

CTGAAAGGAGTTTCAAAAGCCCTTTGAAAGAGTGGCCGCATTGCTGGCAAGAGCAGCTAGTTTCCCTAGG

TTGCAACTCTCATTTATATGTGTAAGCTCTGATCTCCTTGCTTAAACAAAAATAGAGAGAAAGAAAAGAA

AAAAGCAAAAGAAAAAGGCCTTATTTACTTTAAAGTTACACCTTAGACTACTGTTGTCTAAACTTGTGTC

CTGTGGAGCAGTTGACCTGAAAGAAGAGTTCTGTGCTCAAATAAATTTGGGAAACTGCACGTTCTATCCC

TGCTTGGTTATTTACAATGAAGTTACCTTGGCATAGAAACATCTCTGAAATTATTCAAAATTGTTTCACT

TTTCTTAACATCCCATAGAATATTGGTTCTATGGAACATACAGTACTTTGGAAATATATGCATGTGATAA

TTCATCTTATTTTTAGCTTAACTATTTGTACCCCACCTCATTCTAGAGAGGTTGGATAGCAAAGGATACG

CAGGTGGAAAGAATCTCATCCTAGTGGATACATTAAACGGTCTGTCTCCATATAAGGAGCAACTCAAGAC

CATTTTGTTAGTGTGGATTCGTTGATGTGACCTCTGGGAGTCAGGCTCCTCAGTAGGCTCTCTACCTGGT

CAAGCAATTTAGCACACACCCCTTCTTTAGGGACCTCCCAGTAGATCTCCATCTTTGGGAGGAAGGAGAT

GACTTCTTGCAGCTCATTCAACAGGAAAAGGCTTCTGAGTGTGTAAATATACACTGTCACTGTTTTTATT

TGGAGCAGATTTCATCACAGCTATTTTCTAAATGGCTAAACAAGCATTTCCCTGGGTATGTTCCATGGAA


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TATTCATTTTGTAGGAAGCTCAATGATAAAAGAGTCGCATTGTCAATGAGACCAGGAAACTGTATATTTA

ATTCCATTTTGAAGAGTCTCAATTTACTTAAGGATAGAAAAGGCACAGTTAAGAACCCTGATTAACTTCT

TTAACCCACTTTTCCTAAATGTATCTGCCAGTTTTTGTGTACATAAACCTCTCAACCCTTTGAAGATCGT

GCGTTCCAGGGAATACACTCTGGGAAATTCTGGGCAAGACTGTTGCAGGTTTGCAGCAGATACTAGGCAG

AGCTGATACTAAAAAGAGGGAGCTGGCTTCCTCATGGCCACTCACCAGTCCTGGGGAAGTCGGGGAGGGA

GAGAGGAAGCCTGAGCCTGGAATCCCAGCTCTGCCACTTACAAGCTTCAAATCACTTCACCTCCCTCACC

TCGGTTTTCTTTATCTCTTACGTGGAGAATATAAAACCTACATCTTAGTATTCATTTGAGGATTAAAATC

AGATGTCAAGCTGTTGAAGATGAGGCCTGGCATGGAGTAGACCCTTCTCCTTGATGTTCCAGGACTGGGG

AGATCCAGGGTGATTTTATAAACACATGGGGAGGGTGGGCTGCTGACTAGCTGTGCCAATTCCTAGAAAG

GAAGAGTTTCCACTGCTCTGGGATGAGAGATAATCCCAGGAGGATTGAGGATTACCAAAAGGGGGTTACC

ACTCCAAAAGGAGAGGGTCCATGCTCGAATGTTTGCTAGTGTGCATGTCAAGGACATCCCTGCAAATCTG

AAATCCACATCCTAAATCCTAGCCCCACCACTGACAAAAGATGTGACCTTGGTTAAGTCACTTAACCTCT

GCCAGCCTCAGTCTCCTCATCTGTAAAAAGAGGAGTTGGACTACGTATCTCTCTGGAGTACCCCCAACCC

TCAGATTAGTGTGGAACCAAATTAAGGTTATTCCAATCAATCCAGGTTGAAGAGTTGGTAATCTAATTAA

GGATCAGCTGAATTTTCAAGGTTGAGAGTCAAAAAGAACTGTCAAATAATGTACTTGTGTGTGATGCTTC

CAATTTTAATGCTTTTCTGTGTTAGGAGCATATTTTTAAATATTCAAATGTGAATTATTCACATGGCACA

TGCACTTATAATGTGTGCATTTAACTAAAGTGAATCATCAGCCTATTATTAATTATCATTTAACCAGCCC

TATTCTTTTGGATAAAGGAGAGTGTTAGTAAAAACCAAAGGGTTTGGATCATTTAAGCAAAGCCAGCTCT

AAGCAATTTGGCAAGCCCCTCCAGCTGTCCCTCCATATCTTCCAACAGCTATAACCTGTGCATCCTGTGC

TCTTTCATTTACATATACATATACATATGCAAATAAACCCATGTTCACTTGGGAGTGTGCACACTCATGT

TTGTACACACTGTCCGTGTCCTACCTAATATCCTAGATGTCCATCAAAGTCTTCTTGGGGCAGGTGACAT

CCTCACGGGACCTGAGTTTCCTTAGCAGTTAAACACGTGTTCTTTTCCTAGATCTAAGTAAGAGCTCTTC

CAGCTCTGACATTTGATGTCTGTGCTCTTTACTTAGCTATTCCTTGGCAGAAGCATTGGAGACATGCTCA

TACACATTATCTCACATAATTCTTAAAATCATCCAGGAAGTCTTTTTGCATCCTCAATCCTATTTTAACAGATGATGAAACAGATTTACCTACTTGATGTGTAAACATACAATAATAACTGGCAGTTACAAGCTTAGAAA

CCTGATTCTCTATTCTGAATCCAATCAATTCATTCTCCAAGTGACAACCAGGCACTGGCTACTCACTTTT

CCCTTCTTAATCAGAGTGGTTTTTGTGGAGTTGGGAATCATCTGGAAGAGCCTCCTAGATCATCTCCCCT

CCATAGCCAGGAAAATCTGCTCTAGGCTGAAACATGGGATGTAGGCCACTCATGGGCCAGATACAATTCT

AATGGCAATCAAGATATTATAGGTGACTGGAGAGAGTCTGAAGAAGTACATGTCATTAGAGCCAGGGTGC

CTGGCACGGGACCAAATGAGCAGTCTAGTTTGAGACAATGGGAAGTTTTCTTAGCAGGAGTCACCCTTCC

CCCAACCATTCAGCCATCTGCAGACCAGCCTCCCCGCTCCCCAGATTCCACATGCCTACTCTTTCATGAA

TGAAGGCTACAGTGCTATAAGCATAGACTCACACATCTTTAGAGCTACAAAAGACCTCACAAATGATCTA

GTCTAGTCTCCTCGCTTTACAACATAGAGAAAAGTGGTATGCTCTAGGACACAGAAGGTATGGTCAAATT

TATATTAGGCTTCCTGATTCACTCTTCAGTGTGCTGCTTCCCTGGCCTCTGAAGAGGCGAGGCCCCAGGG

CAGGAAAGCACCTCAGTGGCCCACCAGACTTAGCACCAACACATGAGCCTGCCCAGTCCTTTCGCTCTTA

TGCATTCCCGTCTCTGGCCTCTCACCCGGTATTTGGGCAGCCTTACCCTTGACCCCTTGTAGCTATATCC

TCATTCTTAGATCCTCTGCTTCTTCATTTACTTCTCTGTTGCTGGCCCTGGTTCCCTCTGAACTCTGAGC

TCCATGTTAACCCTGTTGCCTACTTTTCCGTTCCTTTTGAAGTAAATTCTGTGTGTCCTACCTCTCCGTT

CAACCAGGAACCCCCTAATAGCTTTATGACCTTGGTGTGAAAGTGTCACTTAGTCATGACCCGTCCCTACAGACAGCAGAATCTGGAGGAATTAGAGCTTAATGTTAGCATTTTACAGGTCACATCCTCTGATCCCAGAG

CAATATTAATAATGAAATTATGAAAGCTTTTTTTTAAAAAAAACAATTACAGGCAATTTTAAGAATATTA

TTCTAAATTCCCATTGAAATCAAATACGCAATTTTAAAAGATGAGTACAGAGCAAAACTTACTGGATGCA

TTACACAAAGTAAAGTTCCATTTCTAAATACTTTCATTTTTTAATCAGAAAGAATAAAAGTATATTATTG

AGCACTAAACTTAATAAGTATCCTAAGGAAATCAGGAGAAAAGCAATAAAGAAAAGATAAAATAATAAAT

TAGAAAACAGTGGGAATAAAAAAATAAATCGAAGATTTGATCCTTGGAAAATGCCAAAAAAAAATGTGCC

AGACATTTGAAGGATATCACATACTCAAATAGGGGAGATTCTGTTAATTCTGTTAATTATTCAACAGAAA

GCCTTGGGTAAATTTGGGTAAATATTTAGAAAATATCAAGGCTGTGTCTTACCTCACATCATACATAAAA

GTAAGTCCCAAATGTATTGAAGAGTTAAATATTAAAAAGAAAATGTTAAGGGGAAGATGTAGGCAATATT

TCCTTGATCTCAAGACAGGAAAGGATATTTAAAGAATGAAATCATGTCTTTTGCAGCAACATGGATGGGT

TGGAGGCCATTATCTTGAGTAAAATAACTCAGAAAGTCAAATACCGCATGTTTTCACTTATAAGTGGGGG

CTAAATAATATGTACTCATGGACATAAAGTGTGGAATGATAGACATGGGAGACTGAGAAGGGTGGGGGTG

TAGGAGGAAGGGAGGGATGATGCAATACTTAACGAGTGCATTGCACACTATTCGGGTGACGGTTACACCA

AAAGCCCAGACTTCACCACTACACAATATATCCATGTAACAAAACTACACTTGCACCCCCTAAATTTATA

ATTTTTTTAAAAAAGGATTAAAGGCAGGCCAGGCGCGCTGGCTCATGCCTGTAATCCCAGCACTTGGGAG

GCCGAGGAGGGTGGATCACGTGAGGTCGGGAGTTCGAGACCAGCCTGACCAACATGGTGAAACCCCGTGT

CTACTAAAAATACAAAAATTAGCCGGCACAGTGGCACATGCCTGTAATCCCGGCTACTCAGAAGGCTGAG

GCAGGAGAATCTCTTGAACCCGGGAGGCGGAGGTGGTGGTGAGCCGAGATCGTGCCATGGCACTCCAGCC

TGGGCAACAAGAGTGAAACTTTGTTTCAAAAAAAAAAAAAAAAGATTAAACGCAAAGAAATAATACATAA

TAGGAGTTGATGTATTTTGTTAAATACAAATTTAAACTTCTATATGTTAAAAATCATTAATGAAAAGGCA

AATTGGTAATCAGTAGGAAAAAACTTTTAGCATCAAAAGAAATAGGAAAAGATGAAGTAATATCCTTAAT

AAATAAAAAGTGCTTAGAAAGCAACAAAAGGGGTCAAAGGACATGATTTCATAGAGAAATAAAAATGATA

ATTTTAAATGTTGGTGAGGATATGGTCAGATAGGCATTTCCTTACTCAGAGTTGGACATGTAATTTGGTA

CAAGTCAGCAGTAAAGAACTAGAGATTTAAAAACCTTCTATAATCTAATAATGGTACTTTTAGAAATCTA

TCCTAAGTCTATCATAAGGAAATAAGTAGAGATAGGAAAAATATTTATATATAAGGATGGTTATAATCAT

GTTTATAATAGTAAACATTGGAATCGATAATTTAAAAAGTTACATCATGATATATCCATAATACAAAACT


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TACTCATCTATGGAAACTATATTTTTGAAAAATTGATTGTCATGAGAAATTGTTCATGATATAATAAGCA

AATGAAAAGAAGGATACACAATGATATAATATTACATCAATTTTATAAATACATATGTGTATATATCATA

TATGCATTATGCTTATGCATATCAGTGTCTTTGGGTAGTATGATTATGGTGCACTTCATTTTCTTCTTTA

AGCTTTTGTGTTTTCCAGAATTTCCACAATGAGCATATATTATTTATAAACAGAATTCACCAAAGTGTAT

TCAAGGCTGGGTACGGTGGCTCATGCCTGTAATCTCAGCACTTTGGGAGGCCGAGGCGGTTGGACCACTT

GAGTCCAGGAGTTCAAGACCAGCCTGGGCAGCATGGTGAAACTCCATCTCTATAAAAAAAAAAATACAAA

AATTAGCCAGGCTTGGTGTTGCGCTCCCGTGGTCCCAGCTACTTGGGAAGTTGAGGTGGGAGGATTGCTG

GAGCCAGGGAGGCGGAGGTTGCAGTAAGCCAAGATCGCGCCACTGCACTCCAGCCTGTGTGACAGAGCGA

GACTTTGTCAAAAAAAGAAACAAAAAAAAAAAAACTGGAAAAACCTCACAAAGCGTGTTCAAAATTTTCA

AACTTTCTACTTGAAAAACACAGATTGATATTATCTGGATGTGATTTTAAGACTGCTTACTCTAATTAAT

TCCTCTAAGAAAGGCATTATTGTTTAATTACATTTCTTAAATCCGTATGAGCTGAGTGGTGTTATTATGG

CTGCTCGCCAGAACGTGGTTATTATGCCATTATGTGACCTGGGACCTGTGCTGAGAGGCCACCCAGTGTG

TGGAAAAGGGTACTGAACCAGGGGTCTTGGGCCTTGCGACCTCAAGGAAAGTGTTTGGTAGCCTTCTGGG

CCTCAGTTTCCTCTTCTGTCAAATAGATCTTACCTGCTTTACTACTTTCACAGAATTGTCTAAAGACCAA

ATAAGAAAATCCAGGCAGGAGTCTATGACATGTAGGCTATTATGAAGCCAAAGATCATTATTCAAAGAAT

AAGCTAGTACCTGCCTGGAATTCATAGTTCATATAAATGATTTTTCTAAATCTCCCTCTTGGTAAGGAAA

CATACTCCCGTGGTTGCAGAAGAAAAAAGCCTCCCCTCTCCTCCCACAGCCCCTTTTCTTACTGAATTAA

TAAGTGCACAGCCCTTTGGGGAGGGTGTAGACAGATCAGGCACACCCCTGTGTCCACCTCCACCAAAATT

CTAGGGGAAAATGCCTGGCTTCTTAGGAAAATGCTTCCCTAAAAAAAGAGGAGAAACCTCAAGTGTTCCC

ATGGAACTGGGGCAGAGGGCAAATTCCGCACAACCTCTGCACAAACCCACGGGCTGGCTGCTTGGCAGGC

CTACAGGGTCCAGATCTCTGATCTGTGGCTCAGAGTAACGAGGTCATTTGGATGGTACATTGGTTTCATA

AACCCCTCCATGATGCTGCTGCTGTTGTGAGGATAGTTGTCACTTCCAACTCATATTATTGCAGACTCTA

GGCTACACGTAGTTATAGGGACAAGAAAGTCCACAGCTCCTCCACTCCCCACACCAACGGCTCCAGGCAG

ACTTGCTGCAAGGAGCAGAGACCCCTTGGTCACCACAGGTAAAGGGGACAGTGTTTTGACTGACTTGGCAAGCTTACCATGTGCAACCCTGGCTGCATATGAGTCTCCTAGGGAGCTTTTTAGTAACCCAGGTGACACCC

CACGTTTAGAATTTAACCAGAATCTCCAGGAGTGGGAACCAAGTATCAGTATTTTTAAAGCTGTCTGGGT

GATTCCAAGAGCAAGCAGGATTCAGAAGCATTGGCTCAGGTTTCAACACAGATCTAGGTATCTCTCCCAC

ACCAGTCTTCAAAAAACTTATCTTGGTGGGTTTTCCACCACAATTCTACACTCTCCTAAGCATTCTTTGC

ACGTAATTTTACCTACCATGGATCCAATTCAACCCTAAGGCATCCTTTATCCTTTAGCTTCTCTACCGGC

TGGCTCCATTTCTCAGTCTGCCAATTCCAGATCCCCAAGAAGGGTGTCGTCTTAGCCCAACTCACCTTTT

TAAACCAGGCTACTTGGGCCATGGGATGCTGGTTGATTTAGAGACTGGCTACTCTGTGGAAAGGGACAGA

GGTTGTGCAGTGTAGAACACGGCCACCCTGGTCTGCCCCAGTTCTGTTTTTTGTGTAGGTGGGGTGGGTT

GGGCACGGTTTCCCTTAACAGAGACTGTGGAATACTTTAACATATCTGGTTCAATAACAAATTATAATAA

TGAAATCAAACATATTTAGAGGAATCCATACAAATTAAGGGTCAGAGTTTCATCCTCTGTATAGAATATG

ATGTAGGAGTCTTTTTAAGTATACGTAGGATAATAAAATGGATAGCCCACTCAACTATCTTTAGAATGTA

TGTATAATTTTATACATCTTTTTCCATAGAAACTACAATTGAATTTAGCATTGAGAGATTATGGTATTCA

TTATTATCTTAGCCAGAGGGTGTTTTTTTAGCTTTTATAAGAAACTTTTAAATTGAAGTATAATATACAT

AAAGAAAAAGTGCACGTTATAAATGTACATCTCAATGACTTTTTACAAAGTGAATACCCTTGTAACCAGC

ACCCAGGTCAAGAAACTCAATATTATCATTACCCCAAAAGATGCCCCTTGTGTTCTCTTCCAATTACTCCTTGCCTCCAAGGGTAACCACTCTCCTGATTCTAGCAGCATAGATTAGTTTTTGTACTTTATATAAGTACA

GTCATATAGGATGTACTTTATTGTGTTTTGGCTCCTTTCCTTGAATATTCATCCTTAGTTTTGCATATGC

ATTTGTAGTTCTCACCAGAGGTTTTAGTCCTTGAAATGTAGTTCAACAAACATTATTCAGCCAGGAACTG

TGCCCGGGGCTGGGGACACCAAAACAAATAAGGGCAAATTCCTGCTGTAAGAAATATTTAATCCAGTAGT

CTCGTAATGATCAGAATTTAGTGTAAGGTGAATTCCTCTTTGTCCAACAAATATTTATTCAGTGTCCACT

AGAGGACAGGCGCTGTATCACAGGTGCTAGGGATAAGAAATGAACAAGCAGACAAAAAATCTAGCAGAAA

TCCTCTCTTTTCTTCCCGTGACGTGCATGGGCAAGTTCTGCCCACTAATATTCATTTCCCACTATGTCCT

GCATCTGATTTAACATAAAGGGAAGTAGCAATGGAAACTATTTCTTCTGGCAACTTGGAATATGAGAAGT

CCCTGGTCCTTGGGCCATTTTTCAAATCAGTGAGTGTGGGAGGTATAATATTTGTGTGTACCAATTTCTT

CCTTATTCCATTCTCTCCACTGCTGATGCTGCCTATACTGAATGCAATGAAAGTCTGGAACCTAAGGAAG

CCTTTGGGTGTTAGCTTACCTTGGAGTCAAGCTGAGCAGTCTTCTTGTTTTCCAGAGCCATGAAGTGAGA

AGAGACACAATTGCCAAAGCTGTGATGGAAATCATACAGCTTTGAATTTGTTTTAGTAACATGGAATTCT

AACATGTGTCACTGTTCATTAGTACTGGCTTTTCAGAGCCTCGTGAATTACTTGGGTACAAATCCATGAC

ATTAGAGGCATGAGGGATTAGAAGACAATCCAACACCACTCTAGGATTGATAGTTTAGGAAGAAATGCAA

GAAATCATCTCATTTTGTTTGGTTGGTTCATTCCTACCCCCCATTCTCCACATTTTTATGAAAAATTTTA

AGTATATATAAATGTAGACAAAATAGTAAAATTCACTCTTATGTATCCATCTTTCAGCTTCAAAAATCAT

CAACTCATGCCAATTCTTCTCTAACCCCTTGTTGTCCCCCTCCTCTGATTATTTGAAGCAATCCCAGATG

ACAAATAAATTACTCATAAATGTTCACAAAGTGAGATCTCCTAGTTTTAATTCCTGTAGTTCACAGGTTC

AGCGGTGAATTCACTAAGCTAGTTAGTGGTACTTATATTTAATCCCTGGCTTCAGAAGTAAAAGTGATAA

GCTTTACTAACAGAATTACTATTATTATTATTACATTATGACATAATATAATATATTCTTGTACTGTTTG

GCCTAAAACTACCTCTTTTAAGCCTCTCATTCAGTTCTCCAAGGAGTTCAACAGGGTGTGGGATGGCTGA

TTGATGTTCTTTTTCATCAGTAATTTCTAAACCAAATCCTTGTGGATTTTGAAATTGCAAATATATTTGT

CCAAGTAAAAGCTTCAACTATTTGGTAATAAAATGGGTCTAAGACTCTTCCCAAACCTCATGTTTCCCAT

TTTCAGTCTGTGTGCAAAGGAGGAGGTTGGCTGTTGTTCATGGAGCCAGTGTCAACTGCCTGTCTGTTAC

GAGATGTCACAGCACAACCAGGCATGCAGCTTACTTTTTTTTAGGTTTCCCAGGCTCAAAACCGCAAAGT

ACCATTGTTTTTGCCAGTTAGAACACTCCAGAGGTTTCTAGAACAAGCAGAAAAGATTGTTAGTGCCTTT


7/28

GTCATGAAAATATGTAAAATGTTGCTTTGGCTGCTTTGGCTATCATAGCTGCTCTGATTGTATCTCAAAA

TGTCACCCAGGGTATGTGGCAGTCATTGTGAGGAATCGGGCACCAGGCACCCCTTGATGAGCCTTTGATG

AGGAGATGATTAGGAGTAAAAAAATGCTGCATAGATTATCTGCATAACTAACACTGTAGCAGACAGCCAT

GCAGACATTTTTCTGTATACAACTCCCACTCATTTTTCTGAGAGATAAAAGCAGCCAAGATTGACAATCT

GTCAGTTTCACCATTTTCATTGTGTACTTTTTCTGGGCAGGTTATTCACATCGAACTCCTTTGATGTGAT

CAGTGATGATGCTTTTATTGGTCTTCCACATCTAGAGTATTTGTAAGTAAAAAAGCTTTTTTAAAACATG

ATGATTCAGGACAAGTACTCTCAAGTTCCTGTAACTGTTTGACAAAAAATATTATAACTTATTGCAGATT

CATAGAAAACAACAACATCAAGTCAATTTCAAGACATACTTTCCGGGGACTAAAGTCATTAATTCACTTG

TAAGTATGAATGTTGCTATTACTTTTTAAGCTTGCTAATGGACAATGCAGTTTGATCACCTGTGGTTAAT

GCACCTACTTTATGAGTGTCCATAAAAATTTAAGAAACCCAAATGACTTCTCTCCATGCACACTTGCCAT

CTTTCCCTGTCATCTGTCAGAGGGTGTTCAATAAATTGATTACTATTAATATTTTTATCCAAAACCAACC

ACAATTAGAAAAGCAATCTAATGCAGGGAAATTGTGTGCCTGAAATAACTTCTTTTATTATCTACATCAT

TACTTGCTTCATGGATCATTATGAGTTGACTGTATAATTTGATATCAGCTTTTTTTCCCTCTATAAGCCC

TCACTTTATATACATTTAAACATAATATAGCCACAGGCGATGTCTTCATAGTACCTGATCAACTTGTTTA

TCAGTGAAATATTTAATTACTCAATGGATGATTACAGCTAACAGCAGTTGTTCTTAACAGGGAACAATTT

TGTCTCCCAGGGAACATTTGGCAATATCTAGAGACATGTTTGGTTGTCACAACTGGGGATGTAAATGGCA

TCTAGTGGGTGAAAGGCAGGGATTCTTCTACTGCTTAGGACAGCCCTTCACGACCAAGAATTATCCAGCC

TAAAGTGGCATCGTGGGCAGGTTGAGAAACCCTGAACAACAGGACCCAAACAATTTGTTTCTTCTAGCCT

CCCTCACCCTCTACAGACAAACACATTCACACACACACACACACACACACACACACACACACACAGGCAC

ACATGTGCATACACACACACACTCACACACACACTCTCACATACACACAGATTATTTTAAGGAAACTAGA

AGAGCATGGAAAGAAAAGGCACTAACATTTACATCACTTTTCATCTAATCCTCTCAATAATCCTGCCAAA

CAGGCACAATAATCCCTGTTTCAGAAATGAGGAAACAGTCTTGGAGGGGATATATGCCTCGTGAGCTGAT

TAGTTACGGAATTATGAGAACATCTACTTAATTGTTGAATTGCAGTGACTCTTCATCCTTTCAACAGCTA

TTTCTCAATCTACCTAATATGTATCTTATCAGTTCTAGATACAGATGCAAGAGATCCAAGTGTCATAGTCATTCTGTCAGCTTTAACCTGTTCTCTCATCATACTTCATTCCCAGCTCTGCTCTAGGCCCTAGGATGCAG

CAGGGAACAAAGGAGACAAAAATGCCTGTCCTTGGACTGAGCCTGATTTCCAGTGTGTCCACGCGGTTGT

CACTCTGCCTCCACCAGGCCCCTTTCTCTCCTGTTGCTTGTTTTGTAGCAAAGAGAAGCTAATAGCCAGA

TATATTTTACAAAATCATGCCTTTCAAGGCTTCTGTATAGAGTTATTGTAATAAAAAAACAGTGTTTGCA

ATACTACTCTTCATGTCAATGACATGATATGATGCAAAGATGGCTGTTTACAGAATGAATGCTATGCAAT

TTTATCACAGAGCTCAACACTGCCAAACCTCATTTTTCAGACAACAAATAAACAAAAGAAACAAATATAT

GGAAGGAGAAATGGAAATTCATGACCTCAACTTGAAATCCACTAGATTCACATACATCCCAATCCACATG

GCCTCTGTCCAGTGCTTAGCATCATGAGAGCTGTAGGGAGGATGCACAGCCCAATTCATCCAGCTGTGTC

TCCTCTCCAGCCTAAAAGCCTGTGGTTTCTCTCAGGCTCCATGCACAGAACAGGAAAAAATGTTTCCCTG

TCTTGGAAGGAAGGAGGGAAGGAAAGAAAGAAGGAAGGAAGGAAGGAGGGAGGGAGCGAGGGAGGGAGGG

AGGGGAGGGGAGGGGAAAGGAGGGAAGGAAGGGAGGAAAGAGGAAAGGAGGGAGGGAGAAAGAAAAAGAG

GAAGGAAGATGAGAGAGGAAGGGAAGGGGGAGAAAGGAGGGAAGGGGAAGAGGAAAAAGGGAAAGAAAAA

GTCTGTTTGACATCCTAGTGTAGGACACCCATTTTGTTTACTGGAGCCTATGATGTGTATCAAATGAAAT

GGGAATTTAAATATGGGTCTTAATGATGCCCTTTCTTTAGCAGTATGGAGCCTGTAAGAGAGAGAGACTG

ATACAGAACACGCTTAACATTCAGAAAATTTCAGGTTCGAGGAACACCAAGGGCAGCCTTCAAAGAGAGGCATGACTCTTAACAGGCAGTGAAAGAGAAGTCCCACCTCTCTGAGCTGGTGCTGGAGGTAGGAAGGTGTT

ATGAGGGAACAGGGGTTAAGGCTGTGGCTAAATGAATATGACCCTTAGGTCTCTTGTATCTTTAGCTAAC

ACTTATTAGGTTGACTGATACGGCATTGCCAATGTTAGGCTGTTTTTTATCTACAAAAATGGCAATGCCA

TATGGTTCATCTTAAATAGTTTCTAAGATGTGACACATGCTTTACAAGGAGTAGGGCCTACAAAGATGAG

TAAGATCTAGTCCCACCTTAGAGAAGCTCAGGCTAGCAAGAGAAATTGGACAAATATTTTCTCACTGAGT

GCCTTTGTCCCCAAGTTATGTTCTCCTTTCAAATTATGCTATTCTTCATGGTACAATTCCTTCCTTCCAT

CCTTCATTCTTTCCTTCCTTTCTTCCTTCCTTCCTTCTTTTATTCCTTCCTTCTTTCCTTTCTGTCTTTC

AAGGAGAGATGGAGTAGGGAGGATCTGAAACCCAAATTTCCCTCTGCCGGCTCAGTAAGTCAGGTTCATT

TTCCATTATTTATGGCGTATTAATAAATCTGGCATTTGTCTGAGCCATTAGTTTCCTTTTTAAGACATTA

GGCTTCAAAGTGCACTTTTCTCCACCTCAGATCAATCCTTCCCAATCAAGGCAAACATTCAAGCTGTGAG

GAATTAGTACCTCACCCTCTAACCTGCATGCATTGCAGGAAGAGGTTACAAAGCTTTCTCATATTCTTGA

CTTCATCATAGTCTCCTGACGACCCCGTGAAAGAGACAGGGCAGTAGCACTAGGTTCATAGATGAACGAG

CAAGTGGAGGTATACCATGAGTTGAAGCTGCTCCCCAGTTACTAAGTGGTAAAGCCAGACAGCTCCCACC

GTCTTTGATGAGACGTCCAGTGCTACGTCCACTGTGCCAGTTACCGCAGGACCAGATAGCTTTTATTGAG

CTGGCTGGATCCTTCCATGGGACATGATTTGAGGAGAAAATATGACTAGAGAAGAAAGAAAAGATCCTGA

AAACAGGAAACCTACCCTCATATTTCATCTCAAAATGCAGATAGTTGGGATTAGACGTATACTTTCAGGT

CCAGCTGGTTCCCACTCTGGCCTAACATTAAAGCCACTCCCTTACCTGCGCCTTTATATAAATTTAGTTC

ACGCCTAAGAAACAATGCACTTTCTCACCTTCTTATACAGAGATGTCAGTAGATTTCTCTTCTAAGAGAC

ATTTACAGATAACTTAAAAGTTATTATAGGCCGGGCGTGGTGGCTCACACCTGTAATCCCAGCACTTTGG

GAAGCCAAGGAGGGCAGATCACTAGGTCAGGAGATCGAGACCATCCTGGCTAACATGGTGAAACCCCATC

TCTACTAAAAAATACAAAAAATTAGCCGGGCGTGGTGGTGGGCGCCTGTAGTCCCAGCTACTCTGGAGGC

TGAGGCAGGAGAATGGCATGAACCCGGGAGGCGGAGCTTGCAGTGAGCCGAGATCACGCCATTGCACTCC

AGCCTAGGTGAAAGAGCAAGACTCCGTCTCTAAGAAGTAAATAAATAAATAAATAAATAAATATAAAAAA

GTTATTATATATACCTGGCTATCAGGCGAGATCCTCCCCTCCCCTGCAAATTAACCCTTAAAACCCTGCA

AATTAACCCTTAAAAAGGGAGAGAGACTTCTTAAAGTTAAGTCCTTTCAAAGCCTGTCAAATGTTGGGAT

TCTCAATTACTTTGTTTTGAATCATTGTTCTAATGTTATGCATGTTTCACTTTAATGTTTGAATGGTTTG


8/28

TATATTTTAGTAATCTTTTGTATATTTGAATTTTTCTGATGAATATATGTTATTTTGGTAATCAGGAAAA

CATGAATAAAAAATTAGTTTATGAATAAAAAATTAATTTATGGCCAATGATGACAAAATCTTCAAACATT

ATGTATTGGCTTCTAGTAATACCTATGAGTCTTTAGTAATGATTGCTTTGTGTGCCATTAAGTGTCACTG

TGGCTAAGGCCCAGTGGAGCCAGCATTGTTTGCATGCATATATATAAATATTTGGAGAAAATTATCATCA

ATCTATATGTATTGTAGAGTATCCAATGGTTGCTCAGCACTGAGGGGGTACAAAGGACTATATAACAGTC

CCCAAACTCAGGATGCTTGTGTGTTCCCAATCAGTTGCACAGGATGTCTTTGTTTTAGCCTTCACATTGC

CTTATATGTAAAGAGGTAGTGCAATGTAGCAGCTAAGAGGGTGATCTCTGCCACCAGACTGCCTGGGTTC

AACTGTCTCTCTGCCAGCTCAATAGGACAAGTTTATTTTCCATTATTTACTACTTATTAATAAATCTGGC

ATCTATCTGAGCCATTAGTTTCCTTTTTAAGACTTTAGGCTTCAAAGTGCACTTTTCTCCACCTCAGATC

AGTTCCTCGGCTTTGCACCTTAACAGCTGTGGAATTTGGGGCAGGCCATTTAGCTTCACTATGCTACAGA

CTGGGCATGTAAAATGGGGTTATAATAATAATCTCTTAAAATGGGATGGGGAATAACAAGGCATTTAAGA

GTATTAGTGCCCAAGGTTGTCTTGAGATTAAGTCAGTTAATAAATGCAAAGTGCTTAGAACAGGGCCTGG

TATGTAGTAAGCACCACTGTATAACTAAAACTCACTGCCCAACCTCCATTAGTCCTGGATCAGAATTCTA

AATGCTATAGTGTATATACCATTTAAACATTTTCTGTGAAATTTAAGTAACTACAAAGTGCTCAGAACAG

GGCCTGGTATGTAGTAAGCACCACTGTGTAGGAAAAAACTAAAACTCACTGCATAACCTCCATTAGTCCT

GAATCAGAATGCTAAATGCTACAGTGTATATCCCCTTTAAACACTTTCTATGAAATTAAAGTAACTGCAC

TTGCACCGCCGCAGGTTCAGAGAGACACAAACCCAAGCTGAGAATCTGCATTGCAGGGGGGCTGGTGCAC

CCCAGATGGCTGTGGGCGATGCTTTCTTAGCAGCAGAGCCCGGTGGCACTGAAACAAACGCGGTGTTTGA

GCCAGTCTGGTCTGCCTTAGAGAGAAGACTTTCCAGTGGGTTCCACAGTCACAATCGGAGGTTTTCTTGG

GTAAATGATGAAAACACCAAAGGGCAGGAAATGGTCATCATTTCTGTGAAGAAGGAATGGCCGTCTGCCT

TTGAGAACACTTGACCTTACTCAGCCAGTTTCAAGGTAACTAGACATTCAGCTGCGCAATATCTCAGTTG

TTTTAAAGAATGTTTCTGGCCAGGTGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGT

GGGCGGATCACAAGGTCAGAGATCGAGACCATCCTGGCTAACACGGTGAAACCCCATCTCTACTAAAAAT

ACAAAAAATTAGCTGGGCGTGGTGGCGGGCGCCTGTAGTCCCAGCTACTCGGGAGGCTGAGGCGGGAGAATGGCGTGAACCCGGGAGGTGGAGCTTGCAGTGAGCCGAGATCGCGCCACTGCACTCCAGCTTGGGTGACA

GAGCGAGACTCCGTCTCCAATAAATAAATAAGTAAATAAATAAATAAAAGAATGTTTCTTAGGTGAACTT

TGAACCAGGACCTAGAGAATGGTGCTTAGTTGAAGGCAACTTTAAAGAGCCTCCACGTTGCCTTGGGATT

TCTACCACAGTGGGGCTGTGGGGAGGGAGGGTCCTTCCTGAGGTGGGGGTCCACACCAGCTGGTGGGGAC

TGCACTAGTCACTCACAGGGCTTTGAGCTTTCTCCCCCAGTGCCTTGGCACAGGGGGCCTCAAAGGAGCA

TCCTCTGCTCTTTTCTTTGCCTAGATATGTACGCGTCCTCTCGTCTACTCCAGCCTGCCTCATTCATTCA

TTCATTTAAAAGTATCTATTAGGCTGTGTGCGGTGGCTCATGCTTGTAATCCCAGCACTTTGGGAGGCCA

AGGCGGGCGGATCACTTGAGGTCAGGAGTTCAAGACCAGCCTGGCCAACATGGTGAAACCCCATCTCTAC

TAAAAACACAAAAATTAGCCGGGCATGGTGGCGTATGCCCGTAATCCCAGCTACTTAAGAGGCTGAGGCA

GGAGAATTGCTCGAACCAGGGAGGCGGAAGTTGCAGTGAGCCGAGATAGCGCCACTGCATTCCAGCCTGG

GTGACAGAGTGAGACTCCATCTCAAAATAAATAAATACATAAATAAATAAAAGTATCTATTGAGGGCTTA

CTTTGTGCCAGGCACTATGCTAGCACTACAGATAATGGAAAGAGAACCATCCTTCTAGTACTCATTGCAG

AATTATCCTAGAAATAAAAGAACATTGATTAAATGTTTCCTCAAGTCTCTCATTGACTGTGTCTTCACCC

CTCTCCCAATCGGCTCCACCCCACCCCAGTCAGATATTCTAGTGCCACCTAGTGTGACCTCCATGCCCTG

GAAAAGCCTGTTGTCAAACTCACTGACCCCTAAGTACGTGGCCTAAAGTATCACCTATCCTAGTGTCATCTATTAATTTTAAAGATGAAGCCATAGCCTCTCAGTGAAAATGACAAAGCTGTGATTTAAGAGCAAGAATA

GGACTTGGAGATCATTCTGACCCAGTGATCATTCACTTTATAGAAAAGGGAATAGCCTGAGCTCAAACTC

AGATATCCACTTCCCTGTCCACGTCACCCCTGTACTCTGTGGCTGAGTTCTGGGCCCTAAAGTGAGTCTG

ACTGGCAAGGGGTCCACTTTGGCCAACACAGGAGCCTGGTACTCCTTAAACCAAAACATGTAGAAAGTCT

TTTTCCTGACAACTCTGGTGGCTACCTGGGACTCCTTGCCTCTCTGTCCTTCATAATTTTTCTTCCTCCT

ATTCCTAAGAATTAAGAATTCTTATATCTAGTATTAAAATTCAGCTCTGCTTAACAGCTCTTGGCTAACA

GATCTTTGCAGAGGAAGGAGGGTCCCCTACTGCAATTCAGGGTGACACTCTCTCAAGTCGTGACACTCTC

TCTAGTCATGACACTCTAGAGGAAAGAGAAGGACTAGACACTCTGTGGGCCAGGATCCATAACATGATGT

TCCAGAATCACTTGCTTTTGATGGGCTCTGTATTAATGGCTGGAAGAAAACATGACTAAATCTTAACAGT

GGTTACTTCTGCTATGATAATTATTATTTCTCTCCTTTTTTAAAAAAATAATTTTTGCACTTTCCAACTT

TTCTTGAAGTGAAGAAATAATTATTATTCCATATATATGTGCATATGTAGTGTGTGTATATGTGTGTGTG

TGTATCAATAAAAGTAAAAGATGGGACTTTTAAGAATACCAATGCATAGGATTATCCCTACTAAGAGAGG

CAGAAAGAATAGATGATCTCAGCTTCCTGAAGCAAATATTTTAAAGTGTTTAGATATTTAATATCACTGT

TTAATGACAATAACAACAAAGAAAAAGATTAGTTTTGTGGTCTTAACACATAAGGTTTAAAAATTCACCT

GCAGATACAGTTTTTCCTGGAATCCATTACAAAGATATGTATATAAAAATATTAGTAGCTACATGTGTTA

ATTCTCACAATAAGTGAAATTCATATCCTTTACTCAGTTTTGCAGATGTCAAAACAGAAACCCAGAGAGG

TGAAATTAACTTGGCTAAGGACACATTCCTAAGAGTGATGACGTTCAAATTTATTCCCTGGTGGATTTGG

ACGAAGTTGGCACTTAAACCACTATACTCCCCTAAGTGATGCAGGAAAGAATAGCTACAACCAGTTTTAA

AAATACTTAGCACGTATAGCAACTAGAGCTTCTGTTGAGGAAAAGTTAATAATAATATTATTATATCATT

ACTCTGTGAAGCTGGGAGTGGGATGAAGACAGAACTGGGAAAATTTTATCCAGGTATTTTGCTTTCTGGT

AGCAAAACTCGGTGCAGAGGTGGAATCTGAAGAATCAAATAATCCTAATATCAACCCTAAAATAACCCTA

ACCCTAACCCACAAAGTGCTATCTCAGTCTCTCTAGCTGTTAAAATTCCCTGATAGACACAGGATCTCAT

TCTACTTACCCCTTTTTTAATGACTAAATGCTGAGGAGGCTTCAGGGAACGTCGCGTGACTTGCCCTTTT

TTTTTCCTGTTGCCCCTGAGCCCGGTGCCCTCAGCAGCCCTCCGCTGCAGCAAATCTCCCTGAAGCCCTC

AGATGCCCATGATGATTTGTGGAGGCAACAGGCCCTCATCACAGCTGGCTTTAAGCTGGCGCAAAGAACC

ACAGCGGTGGCTTCAAGCCTCGGCTGCCCTGTAGCCCCAAACCTCCCTAAAGGGTGAGGGCCTGAAACCG


9/28

CATGAGAGTTTTCTAGGAAACAGGCAGCTCCCCGCTGCAGGAGGTCTTGTGAAAGACATTTGCATGACCT

GACCACTCAGGCCCCCGAGTTCGGTAATTCCTAATCTAACCCTGTAGGTAGCTTTGGAACTTGACAAATG

CAGCCAAACGATTGATTTCGAATGACTGAACCCTCATTGGACAGAACCATAGATATATACAAATACTAAG

CAACAGGATCCTTTCAAAAAGTCAACTTTATTCTTTGTTTCTTCTGATTATAAAATAATAATACATGCTT

GATGATAAAAACTCACAACATAAATATGTATTTACACAGAAAAGTGAAAGATTCCAGTAACCCTACACCT

ACCTCATTTTTAAAATCTCCTACAAAATATTCCGTGTTACATATGGACCATAGTTTATTTACATGATCCC

TTATATCTCTTTGTTGTTGTTGTTGTTGTTGTTTTTGAAACAAGGTCTCACTCTGTCACCCAGGCTGGAG

TGCAGTGGTATGATCATGGCTCACTGCAGCCTCAAGTTCTAGGCTCAAGCCATCCTCCAACCTCAGCCTC

CCAGAGTAACTAGGACCACAGGCACACACCACACCCAACTAATTTTTGTATTTTTCGCAGACAGAGGATT

TTGCCTTGTTGTCCAGGCTGGTCTCAAACTCCTGACCTCAGGTGATCCGCCCACCTCTGCCTCCCAAAGT

GCTGGGATTACGGGCGTGAGCCACCATGCCCTGGCAACCTGTTACATTTTTTGCAGAGTAATTCTCAGGC

TCTGTCAGCATTGCTTTCCTAAGTCGTTCTCTGCCCAAATCCCTCTGCCTACTTTCTTTTTATCTAAATG

TAACCTGTCACTGGAGCCTCCCAGAGACTTAGGGAAGCTGTCTGAACTCCAGCTCCCTAGCCTTGGATGT

CTGGAAGCCTCACTCTCATTTCTGAATCTTGCTTCCTCTTGAGTCTGCTTCTCTTAGTGAATCCAGGCAG

CCTTCTCATGCCCATCACTCACCAAACCTAGACATGAAGCTTCATTCTCTCTCCTCTAAGAGCAGTTCAT

TGTGGGCAAGGATTTCATTGAATTTTTGGTAGCGGAGCATCAGAGGGTTGACACTGGGTTCAGCGAATCC

ACCCACCATTTCTCCCTCTGGCTCCCCTGCCTCCCCCACCCTCTGATTCCCAAGGCAAAAGCCTGTCACA

AGAGGTTCTCAGGAAATTTAATGCCTCATTCCACAGCCCATCGGGCCAGCCTGTCCTTCTCAGCCCCATC

TCACAATTCTGGTGAATTAGAAGCCCTCCATCTTGTCATGCAAAAATACTGCCTCTCCATTCTGGAAGCC

CCATAGCTCCAAGTCTGCAGCTCTGTTTTGCCATCTGTTCTGTGGTTAGCTTGCACGTGGATCATGTGAG

GCCTAAAGCTCTACTCCTTTGGGCAGGAAGTAGAACTTCCAGATTCACTCATTATTTAAAAGAATCCCAC

AGGGTACAGTGGCTCACACCTGTAATCCCAGCACATTGGGAGGAAGAGGCATGAGGATAGCTTGAGCCCA

AGAGTTCAAGACCAGCCTGAGCAACATAGCAAGACCCTGTCTCTACAAATAAAAAAAACTTAGTTGGGCA

TGGTGGGACACACCTGTGGTCCCAGCTACTGGAGAGGCTGAGCCCAGAGGATCACTTGAGCCAGGGACGTTGAGGCTGCATTAAGCTGTAATTGCACCACTATATTTCAGCCTGGACAACAAAGTGAGACCCTGTCTCAA

AAAAAAAAAAAAAAAAAGAATTCCCCTTGGACAGTAAGACAAGCATGGTGCCTTCTCCTGTATAGCCCCT

ATTGGCAGTAGTAATTCAGGATTTGACTGCTTAATCATTGCATGCCCACTGTCCTGTGACTCAGCCTCCT

CTAAATTTATGCTCTGCAGCCAGTTGCAGTTTTTACCAGCTTCAGAGGAAGGGACATCCACTTAGAAGTT

AGTATGATAACTTTAAGCCACATTGTGCCAGAAAATAAACTGAGACACATAACATGGGAGTGACTCTGGA

CTGGTCCAAGACATCAGAAAATCTCTTCATTCAAACACCAGTCAGTAAGATGAATTATGGAGACATTCTC

TTGAATAGTCTTCCTTAGCAGCATTTTATTAATTTTGCTGTATGTGGACAGCCATAGCAGTTCATTCATG

TGGTCTGTTTCTAAACGTTGTTTCTTGGACAACATACGTACAGAAGCTGTTCTCTTCTGACACCAGCCAC

TCTACTGAGAGTAGTTCAGACACCTGCACCATCCTTGATTATCTCATTTCCTTTTTTCAATAATCTTATG

AGATAAGGTATTATTATCTTCACTTAAAAATGAAACAACTGAATTTCCAAGAAGATACATTACCAAAGTC

ACACAGCCAGTAAATGCTGGAGTCAGGATTCAAACATAGCTCAGAATCACTCCAAAAGCCATGCTCTTTG

TCACAATTGGACCGTCATTGACAATGGAACATTCTGACTCAGTTCCTATTCTTGCATTCCAAGGTTCATT

GAGAACCATTTTCCAAACTAGCAGTAATTTCTAAAACCTAGAAAAACAACATAACTAACTTAAAAATAAG

TTCTAAAGTTCATGAATGTTTGCACTTGAGAAACCTTATATTTAATTAGTGGAGGTAGAAGACATAGACT

TTTGAGAATGTTTTAAAGGGAAGTTGAGAGAATTTTCAAGGGTTTAGAGGCTAATGGTATGGGCTCTTTAGTTTTAGTTTAGTTTTTTATTTTTATTGTGGAAAAAAAAAACACCTCTAAGAAAAGTTTATAACGTGTAT

ATATATGGTGCTGGTTAAAAATAGAAAATTACACTACTTGGTGACCTTCCCCAGTCATACAGCATTAGCA

CTGTGCTATGTCTATATTTGTGTACTAGGGACACATTTCCCTTTCCTTGACATTATCAGGACAATTTTTT

ACTCATTAACCTTTATTAGAATCATTCTAGTGATTTACGGAAGAACAAATAGAAAGGGAAAGGGAAAAAC

ATTCCTGTGATCACAGGAAAAGAACCAGAAGAAGGAGAAAGAGGGGGATGATTAAAGAGAATAGATGGAT

AGGTTTTTATAAGAAAACTTTTTTCTGAGGTGGAATGAATGGTGCTAGAAAGGAAAAGGAGGCGTGGGCT

TTAGAAAGGAGAAAGGATGTACTGGGGAAGAGATAGAGCTACTGGCACTGTGGGTTGGAGGTTTGGTTGC

TCTCCGGAGCAAGCGAGGAGGAAGCAGGCAGAAGGGGCAGCCCAGGCAAGAGGAGGGGGCGCATTTTGGA

GATGGACACTCACCAGTTTGGTTAGTCATCATTTGGGAGATATCCCCTAGATTGAGCGTCTGAGAGTGTG

AATCTCTCGTGTTCTGTTCTAAATGGAAAGATCAATGCCCAGGAATCATTGTTGTTTTTAACCAACATAA

AGTGTTGTTTAAATATTGAGTGCACCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGTGGATCACTGA

AGCTCAGGAGTTCAAGACCAGCCTGGCCAACATGGTGAAACCCTGTCTCTACTAAAAATACAACAATTAG

CCGGGTATGGTGGCGGGCACATGTAATCCCAGCTACGGCAGGCTAAGGCAGGAAAATCACTTGAACCCGG

GAGGCAGAGGTTTCAGTGAGCTGAGGTCACACCACTTCACTCCAGCCTGGGTGACAGAGCGAGACTTTTG

TCTCAAGAAATAAAAGTAAATAAATATGGAGTGGGTGTTGAAGTGAACAGGTTAGGAACTGAAAGGACAA

TAGCAGGAATCTGAGTAGTAGTTCAGAAGAAAAAAAAAGGACCACAAGTCTTTTAGTAGGCTGGAAATGA

CAAAAGAGACTCATCACTAAGCTTTATCATTAAATGCCTTTGTTTAATTTATCACTACAGTTTACATCAC

CTTTTTTTTTTTTTTTCCAGGAGCCTTGCAAACAACAATCTCCAGACACTCCCAAAAGATATTTTCAAAG

GCCTGGATTCTTTAACAAATGTGTAAGAGGACCTAAGAAATCACTGAACAATTAATTAATTTGCAGTCAT

TAACAAGGAAGCCTGGTATTGATTATTATAATTTTTAATTGGCTTTTAAATTAAAATTAGGATTTTTAAA

TCTAAATTTTAACTGGCCAAAAATTTAAATTTACATGGACTAACATTTGAGTCTTCTATGGTATTTATCA

TTGGGAATTCTGAATACATGGCACCCAGGCATTCCTTTGACAAAGTGTGTGTCAATACGGCAGGGAGCGA

TGATAAAGGACTTTGACGGGGTGGGAAGAGACCCGGCTAGAAATTTCAAAATCCCTTTTTTCTCATGAGG

TCCAGGAAATAGGGCTACAAAGGAAAAACATAAAGGAGTCTGGGAAACTGACAGAATAAAGATGAAAGGT

TACATCCTTGGGTTGGTCAATCAACAGAGAAATGGAACAGGAAGTGGGGGAAGGGAGAAAAGTTTGCCTT

TTTTCTCATTAGACTGAACAACAACTCTAAGCTTAATCCCCAGGAATTTGGCTTAAGCCCCAGGAAGGGA


10/28

ATGAACTTAATTATTTTTGACCCTTTTTCAAACAAAAGAGCTTTCAAACTTTGACTTTTAAGCCTCCGAG

TGAAAGATCTTTGCAAGGAATTTGTATATTTTGCTGTAAGCAAAGCAAGTAATATATGCCTAAACTTCTC

AAAAGCAATTCAGCTTCATTATTTGCCTTCCAGAACATTAGAAAGGTATTTAAATGTCATAAGGTGGAAG

ACAGGAACAAATGAAAGGATATATGAAAACAAAAGCTTTTTTAAAAAATTATTCAGGTACTTGTCTGTAG

AATATATATTCAAAACAACTTTTCTCCAATAACAAACAAAAAGAAAATCTGAGTCAAGTACTTTCTTCCA

AGCCCAGTATTTAACTTCAAATCAGTAGCCTAATGAAAAACTTTCTTTGTTCCTTGCAGTATTTCCCCAG

CCCCTCCTCCATGTCTATTACCTCAATTCCTGAATGATATGGTTTAATTCCAGGAGAATGCCCAAATCAG

GATTCTTCCAAGAGAGTCCTGGACAGACCATAGTTATCCTCTCTGGTTTACAGTAGCCTGAAAGGTTGCC

ACTCATTAGTGTGGGTCAGAGTTCTCTTGGGAGACTAGGTCAGTTCTGGGAGTGTCTTGGAAGTTAGAAC

ACACTCCATGGGTGACGTGGGATGTAGCTCATTGGGGGTCCTTTACCCCATTTTTGTGTCAGTCTATACC

CTACACTAGTGAAAGACAAAACAAAAAAATATTGAAATTGGCTCAGTCTCTCATGGGAATCCCAAGATGG

GTTTAGCCTTTTGGACCTACTCTAATATGCCCAAATCAAGAATTATCTTAGAAGTACAAGGATCCATGCC

AACTTGCCTTTTAGTGGATTTCTTGGCTTTCTTGAAAGTATCCTCTAAAAAACATTTTTAAATGTTTGGG

CGTTTAAAAATTATTTATGTGTGGTGTGAAGAGTAGGCAGCACCTATCTTAAGAATTCTGTGTGACCAGG

AAAGGAGGTGGAATTCCTGAACAGAAGCAATGCAAATACACAGAGAACTTGGTGAGTTGGGGTCATATGT

GGATATGTAAATGGTCTATGCTGTATAACTTATTACAGGCATGAGCGATTGTATGCCTGTGTTAACTCTG

CTGTGTCAAAGTCATTTCCTATTTAAACTGAATTTGTAGACCACGGAAGAGGATCAGGATTAATTATGTC

TGTGAGGAAGAAGAAAAGCAAATAGCTCACTTGATTAAATACATTACAATAATCACTACATTCTGTCCTT

TAGACCTGTGCTGTCCAATAGGGTAGCCACCAGACCTTATGGTCACTGAGCACCTAAAATGTGCTCCTAG

TACAACTGAGAGACTGAATTTTAAATTTTACTTAATTTTTTAACAGTTAAATTTAAATTTAAAAGCTGAT

TCTCAGCTCAATTATTGGAAAATGTTAAGTACGCTTGGAATAATTTGGGTATATACACCTATTTTTTTCA

ATTATGAATTTTATGACATCTAAATATAGATCACCTATTTCTGGTAAAATTTAGCATCTGAATTGAGATA

TATTGTAGGTATAAAATACACACTGGACTTCAAAGACTTAGTATAAAAAAGGAATGTAAAATATCTCAAT

AATGTTTATATTGATGATGTGTCAAAATGATAATCTTTTGTATGTATTGGGTTAAATAAAACATATTATTAAAATGAATTATACCTGCTTCTTTTTACTTTTTTAATGTGGCTATAGAAAATTTTAAATTACAATTACGG

TTCATATACTGTTTCTATTGACAGCACAGCCCTAGACTAAGCCGCTTTGGAATTCAAGAGGGAGTAAGTG

ATGAGGTTCCATTGACTGGGTAGTCTTCAAGTGTGCATGGTGCTAACTCTCTGAGCCCAAAGTGAATGAG

TGGTCAGTCAGGTTCCAGGCAGGTTATAGGGCAGGATGCAACGCCGGGTAAGGTCATTCTGCACATGTTA

ATTGTTGATGTAGAACTCTTTCCTGCGTGGGTAGGGCCCTTGTACAGCAAAAGCAGCTGAAGTTTGTCTT

TCAGGGACCTGAGGGGTAATTCATTTAATTGTGACTGTAAACTGAAATGGCTAGTGGAATGGCTTGGCCA

CACCAATGCAACTGTTGAAGACATCTACTGCGAAGGCCCCCCAGAATACAAGAAGCGCAAAATCAATAGT

CTCTCCTCGAAGGATTTTGATTGCATCATTACAGGTAATGTACTCATCATCATTCCACCTCAAAAAATTA

AAATAAGGGCTACCTTTTTTTTTCATGTGCAGGAACTGATATTTTTTATATCTTAAAAACTAGCTGAGCA

ACTTAATTTTAAAAAAATTATGAACCATTGACAATGCTTCATGTGTTTAAAAGTAAAATGGCCATTTTAC

TATTCTCTGAAATAAATGTATTTCTTGTGAATATTTAAGATCTAGCCAAGGAAAGAGGTATTAGCTCACA

GTTACTTATTATTTCCTATTTTTGCAGAATTTGCAAAGTCTCAAGACCTGCCTTATCAATCATTGTCCAT

AGACACTTTTTCTTATTTGAATGATGAGTATGTAGTCATCGCTCAGCCTTTTACTGGAAAATGCATTTTC

CTTGAATGGGACCATGTGGAAAAGACCTTCCGGAATTATGACAACATTACAGGTATGAAAAGCCTAATGA

TATTTTGAGTGGTAATTTAAACTGCTTCAGCCAAGGGCAACAAGGAAAGATGAGTGGTATAGGGGAATGCTTTAGCATTTGAATTCCAACTCTACCATTTGTTAAGTGACCTGGGATTGTTCTCTAAGCCATAATTTCCC

CACTTGTAAAACGGGAATAATATTAATACTTAACTCACAAGGTTGTTAATAAGATCATGTGAACACATAT

TCAAGAAACTTAGCATAGGGTCTAGTATAATACATAAACAGTAAATATTTGATTATTTTTCTTCAAATAA

AAGTATTGGATGGTGAATCATGAGTTCTAGTCCAGGTTCTGCCACAGTCTATTTGGGCAAGCTGCTCATA

CTCACTGACACCCCTCAACCCCTTTTTCTTAACTATAAAATAAGAAGGTTATTTTAGATCAATAAGTCTC

AAATTTGTTACACAAACGTGTCTTCTACAAAATGTTAATGTATGCCTTGTAATGAAAAGGATTTTGTGGT

CCAATAAATTCATGAACCATATCTTGGTCTTGTAGGTTCATAATACAGACATCTGTGGATCTGAGAAGTC

CTGCAGTGAGGAAATTTTTCCAATATTTTTCACCCTTAATTTGGCCATGGAATTTAATTCTTTCTTTTCT

TTTCTTTTTTCTTTTTTTTTCTTTTTTTTTTTTTTTTTGAGACAGAGTCTCGCTCTGTCACCCAGGCTGG

AGTGCAGTGGCACAATCTCAGCTCACTGCAACCTCCAACTCCCGGGTTCAAGCAATTCTTCTGCCTCAGC

CTCCCAAGCAGCTGGGACTACAGGTGCGTGCCACCATGTCCAGCTAATTTTTGTATTTTTAGTACAGACA

GGGTTTCACCATATTGGCAAAGCTGGTATTGAACTCCTGACCTCATGATCCGCCCACCTTGGCCTCTCAA

AGTGCTGCCATTACAAGCGTGAGCCACCGCACCCGGCCGGAATCTAATTCTTTCTATGAAAACTTTTACT

TATCTGGATCTCTCTTTTTTTTTTTTTTTTTTTGAGATGGAGTCTTGCTCTGTTACCCAGGCTGGAGTGC

AGTGGCGTGATCTGGGGTCAATGCAACCTCAGCCTCCTGGGTTCAAGCGATTCTTGTCCTTCAGCCTCCC

AAGTAGCTGGGACTACAGGCATGTGCCACCACGCCCTAATAATTTTTTGTATTTTTAGTAGAGATGGGGT

TTCACCAAGTTGGTCAGGCTGGTTTCGAATTCCTGGCCTCAAGTGATCCACCCGCCTTGGCCTCCCAAAG

TTCTGGGATTACAAGAGTAAACCACCTTGCCTGGGCTTACTTAGCTGATCTCTTAAGTTTCTTTCCCATT

TTAATAATTTTTAAAATTATAAGTCATAAGTTAGAACATAGGGCTCCCTCTACAATTTTTAATATCAGTT

TTAGCTTCTAATACCTTTAAATCTGCTCTCAAGAGCACTCACACCTCCCCATAAAAGGTAACCCTTTAGA

CAAGGCATGGAGGGTCATGATAGATTTTGCTGGTAGCCATCACCCTCATTGCTCAAAGGACCAAGACAGG

TCTGGGGCTTGCTTGAGGCTGGGGTTGCTTAAATAAAGGGATCCCTTCCAAACTGAGACCCTTTTGGAAT

CCTCCTTTCTTTTAGAATCCTCCTCTCTGAAGGAAGAAGGTCATGCTTCCTTAGGCCCCCATAAGTTTTC

CAGTGGACTATAGCAGGGTTTTGTGCGGTCGAAACCAGGCTTTTCTTACTTGTGTATGGTTCATCAATTT

CTTTGAATGACTCTTTAGATGAGCACTTACAAGAGAAATAAATCATACATCTGCAAACTTTCTGAGGGCA

TCTCAGAGCTCATCTTGTCTAGGATGATGTCTTAGTCCCTTCCTGCTGCTGTAACAAAAAATACCTTGAC


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TGCGTAATTTATAAGAACAGAAATTTATTTCTCATAGTTCTGGAGGCTGGGAACTCCATGATCAAGGCAC

CAGGAGATTTAGGGTCTGGTGAGGGCTCACTCTCTGCTTCAAAGACGGTGCCTTCTCTGTGTCCTAACAT

GGCAGAAGGGCAAAAAAAGATCTAACAGACTCGCTCAAGCCCTTTTGCAAGGGCACAAATTCCATTCATG

AGTGTGGAGTCCTCATGATCTAATCACCTCCTAGACACCCCACTTCTTAATACTATTACACTGGGGATTA

AGCTACAACATAAATTTTGGAGGGACAGAAACATTCCAACCATAGCAGATGACAAATATATGCCCCATAC

TCAGTCATTATCCCTTCCTTCACTCTAGACAGGCACCACTAATCTATCATGGGAATCTTTCATGTAGAGT

GCAGACACGGCCACAGAATCCTTCTCAACACAGTTCCCCAGACAATCACACGCAATGAGCCAATCAGTAT

TGGTACATGTGTTGGAATCTGGTGGCCATCCTTAATCTAGTCTAAAGTCTCATTGTACAGAAAAGAAAAC

TGAGCCTCAGAGAAGTTAAATGATTTTCTTAAGATCATACAATCAGTTTAGCCCTGAAAAGAGTCAGAAA

TAAAACTATTTTGCCTATGGATGAAGCCAATTAGTAGAAAGAATTAATGTAGAACTTTCTGCCCCGCACT

AGCGCTGTAGTCAGAAGAGGCCTAAAGCCCAGATTTGTTCAGCTGTCTCTGGATTTTCTAGAGCCAAACT

CCTGCAAGATCAGAATCTACTGATAAATGTCAAACTCTTCCCCAAAGGATACCAAGCTAGGCCACTGACA

GATCCCACATCATTTTCTGTGATTTTCCAAAATAACTTTCAGGAGCAGTGCCCATGGCTGCACCCTTCTT

TCGATTTTTTTAAAGATTCCTTTTCCTTCTCTTCACTCCTGCCACCAGTGACCTAAAGCTCCAGAAAAGT

GACAAGTGGCATCTCCTTTCTTTGCAGGGGAAAGGCAAATTATTCTAGAGCAGGAAGCAGTTCAGACTTA

GAGCAAAACAATTACAGTAGAGCCATGGGCTACCCAGACCACAACGCTAGCCTTTGGTTATCTAAGATCT

TAGATAAACCAAATTTGAAGTCCTGGAATAGCTAACTTGTCCCCAGCTTGGGTTAAAAGCATAGAGATGC

TGGTAGGCCTGGCTTTGAATCCCCAACTCTGCCTTCTGCTACCAGAACAGCCTCTCTGAGCTTCAGTTTA

CTCATGTGGAAAAAGGATAATATTTATCTCTTAAGATTGTTGGGAAAATTAATGAGGTAAATTGAGAAAG

CACATAATAGATGCTCAGTAAACAGTAGTTTTCATTAGAATTATGATTAACTCATTTGTGTCAGGGAAAC

TAATGCTTTCTTTCTGCAAGAAGTAAGAGGAGAACACTCGGGCCATAGCTGTGTGTCCTGAACGTCTAGC

GCAGGCTAGATATGACATTAACAACTCAATTGTTGGCAACAAGGCCCCACGAGGCACAAAGGCACGGAAC

TTTAGGACACTGCTGCCATTGGGCTTTGGAGACCAGCCTTGCCTAATCAACCAAGGAGATCTCTTGTTTC

AGGCTGATTTGGGTGGAAGTTGTATGGCCCCAGCCCGCATGTTTACATGCTCCAAAAGAGGATGGCCACACAACTAATCTCTCCTTTGTCTTTTCCCAGGCACATCCACTGTAGTATGCAAGCCTATAGTCATTGAAACT

CAGCTCTATGTTATTGTGGCCCAGCTGTTTGGTGGCTCTCACATCTATAAGCGAGACAGTTTTGCAAATA

AATTCATAAAAATCCAGGATATTGAAATTCTCAAAATCCGAAAACCCAATGACATTGAAACATTCAAGAT

TGAAAACAACTGGTACTTTGTTGTTGCTGACAGTTCAAAAGCTGGTTTTACTACCATTTACAAATGGAAC

GGAAACGGATTCTACTCCCATCAATCCTTACACGCGTGGTACAGGGACACTGATGTGGAATATCTAGAAA

TAGTCAGAACACCTCAGACACTCAGAACGCCTCATTTAATTCTGTCTAGTAGTTCCCAGCGTCCTGTAAT

TTATCAGTGGAACAAAGCAACACAATTATTCACTAACCAAACTGACATTCCTAACATGGAGGATGTGTAC

GCAGTGAAGCACTTCTCAGTGAAAGGGGACGTGTACATTTGCTTGACAAGATTCATTGGTGATTCCAAAG

TCATGAAATGGGGAGGCTCCTCGTTCCAGGATATTCAGAGGATGCCATCGCGAGGATCCATGGTGTTCCA

GCCTCTTCAAATAAATAATTACCAATATGCAATTCTTGGAAGTGATTACTCCTTTACTCAAGTGTATAAC

TGGGATGCAGAGAAAGCCAAATTTGTGAAATTTCAGGAATTAAATGTTCAGGCACCAAGATCATTCACAC

ATGTGTCCATTAATAAGCGTAATTTTCTTTTTGCTTCCAGTTTTAAGGGAAATACACAGATTTACAAACA

TGTCATAGTTGACTTAAGCGCATGAGACACCAAATTCTGTGGCTGCCATCAGAAATTTTCTACAGTACAT

GACCCGGATGAACTCAATGCATGATGACTCTTCTTATCACACTTGCAAATGAATGCCTTTCAAACATTGA

GACTGCTAGAACCAAGCACTACCAGTATCTCCATCCTTAACTGTCCAGTCCAGTGATGTGGGAAGTTACCTTTTATAAGACAAAATTTAATTGTGTAACTGTTCTTTGCAGTGAAGATGTGTAAATAAGCGTTTAATGGT

ATCTGTTACTCCAAAAAGAAATATTAATATGTACTTTTCCATTTATTTATTCATGTGTACAGAAACAACT

GCCAAATAAAATGTTTACATTTTCTTTCATA

La secuencia del mRNA es la siguiente,


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>gi|171846229|ref|NM_005097.2| Homo sapiens leucine-rich, glioma inactivated 1 (LGI1), mRNA

GAAAGCAGAAAGCTGTTTATTTTCTGTGACATCACTTCACTTTGCCTTCGAAGGCTGGTCTGTGCTCAGT

GTTTTCGTGGTGATGCAAGTCGGCTCTCTCCTCCAGCAGTTGGATCCCTCCCATCTCACAGTACCTCACA

GGTCTCTTCCCCCGAGCAGTGCATTGCTGGAGCGAGGAGAAGCTCACGAATCAGCTGCAGGTCTCTGTTT

TGAAAAAGCAGAGATACAGAGGCAGAGGAAAAGGGTGGACTCCTATGTGACCTGTTCTTAGAGCAAGACA

ATCACCATCTGAATTCCAGAAGCCCTGTTCATGGTTGGGGATATTTTCTCGACTGCATGGAATCAGAAAG

AAGCAAAAGGATGGGAAATGCCTGCATTCCCCTGAAAAGAATTGCTTATTTCCTATGTCTCTTATCTGCG

CTTTTGCTGACTGAGGGGAAGAAACCAGCGAAGCCAAAATGCCCTGCCGTGTGTACTTGTACCAAAGATA

ATGCTTTATGTGAGAATGCCAGATCCATTCCACGCACCGTTCCTCCTGATGTTATCTCATTATCCTTTGT

GAGATCTGGTTTTACTGAAATCTCAGAAGGGAGTTTTTTATTCACGCCATCGCTGCAGCTCTTGTTATTC

ACATCGAACTCCTTTGATGTGATCAGTGATGATGCTTTTATTGGTCTTCCACATCTAGAGTATTTATTCA

TAGAAAACAACAACATCAAGTCAATTTCAAGACATACTTTCCGGGGACTAAAGTCATTAATTCACTTGAG

CCTTGCAAACAACAATCTCCAGACACTCCCAAAAGATATTTTCAAAGGCCTGGATTCTTTAACAAATGTG

GACCTGAGGGGTAATTCATTTAATTGTGACTGTAAACTGAAATGGCTAGTGGAATGGCTTGGCCACACCA

ATGCAACTGTTGAAGACATCTACTGCGAAGGCCCCCCAGAATACAAGAAGCGCAAAATCAATAGTCTCTC

CTCGAAGGATTTCGATTGCATCATTACAGAATTTGCAAAGTCTCAAGACCTGCCTTATCAATCATTGTCC

ATAGACACTTTTTCTTATTTGAATGATGAGTATGTAGTCATCGCTCAGCCTTTTACTGGAAAATGCATTT

TCCTTGAATGGGACCATGTGGAAAAGACCTTCCGGAATTATGACAACATTACAGGCACATCCACTGTAGT

ATGCAAGCCTATAGTCATTGAAACTCAGCTCTATGTTATTGTGGCCCAGCTGTTTGGTGGCTCTCACATC

TATAAGCGAGACAGTTTTGCAAATAAATTCATAAAAATCCAGGATATTGAAATTCTCAAAATCCGAAAAC

CCAATGACATTGAAACATTCAAGATTGAAAACAACTGGTACTTTGTTGTTGCTGACAGTTCAAAAGCTGG

TTTTACTACCATTTACAAATGGAACGGAAACGGATTCTACTCCCATCAATCCTTACACGCGTGGTACAGG

GACACTGATGTGGAATATCTAGAAATAGTCAGAACACCTCAGACACTCAGAACGCCTCATTTAATTCTGT

CTAGTAGTTCCCAGCGTCCTGTAATTTATCAGTGGAACAAAGCAACACAATTATTCACTAACCAAACTGACATTCCTAACATGGAGGATGTGTACGCAGTGAAGCACTTCTCAGTGAAAGGGGACGTGTACATTTGCTTG

ACAAGATTCATTGGTGATTCCAAAGTCATGAAATGGGGAGGCTCCTCGTTCCAGGATATTCAGAGGATGC

CATCGCGAGGATCCATGGTGTTCCAGCCTCTTCAAATAAATAATTACCAATATGCAATTCTTGGAAGTGA

TTACTCCTTTACTCAAGTGTATAACTGGGATGCAGAGAAAGCCAAATTTGTGAAATTTCAGGAATTAAAT

GTTCAGGCACCAAGATCATTCACACATGTGTCCATTAATAAGCGTAATTTTCTTTTTGCTTCCAGTTTTA

AGGGAAATACACAGATTTACAAACATGTCATAGTTGACTTAAGCGCATGAGACACCAAATTCTGTGGCTG

CCATCAGAAATTTTCTACAGTACATGACCCGGATGAACTCAATGCATGATGACTCTTCTTATCACACTTG

CAAATGAATGCCTTTCAAACATTGAGACTGCTAGAACCAAGCACTACCAGTATCTCCATCCTTAACTGTC

CAGTCCAGTGATGTGGGAAGTTACCTTTTATAAGACAAAATTTAATTGTGTAACTGTTCTTTGCAGTGAA

GATGTGTAAATAAGCGTTTAATGGTATCTGTTACTCCAAAAAGAAATATTAATATGTACTTTTCCATTTA

TTTATTCATGTGTACAGAAACAACTGCCAAATAAAATGTTTACATTTTCTTTCATA

La siguiente informacin presenta la regin correspondiente al exn, la secuencia

codigicante (CDS) y la protena traducida.

Mediante la herramienta clustalw se realiza un alineamiento entre la secuencia total del

gen y la secuencia del ARNm.


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Los resultados muestran un score de 100 entre la secuencia A (ADN) y la secuencia B

(mRNA) , lo cual confirma que el mARN de 2366 pb es la transcripcin del gen ILGI1 de

47351 pb.

El alineamiento en detalle se presenta a continuacin,

CLUSTAL 2.1 multiple sequence alignment

EpilpesyDNA TTCTAAAGTTCATGAATGTTTGCACTTGAGAAACCTTATATTTAATTAGTGGAGGTAGAA36000EiplepsymRNA ---------------------------------------------------------GAA 3

***

EpilpesyDNA GACATAGACTTTTGAGAATGTTTTAAAGGGAAGTTGAGAGAATTTTCAAGGGTTTAGAGG36060EiplepsymRNA AGCA------------------------GAAAGCTG------------------------ 15

** * *** **

EpilpesyDNA CTAATGGTATGGGCTCTTTAGTTTTAGTTTAGTTTTTTATTTTTATTGTGGAAAAAAAAA36120EiplepsymRNA -----------------------------------TTTATTTT--CTGTG---------- 28

******** ****

EpilpesyDNA ACACCTCTAAGAAAAGTTTATAACGTGTATATATATGGTGCTGGTTAAAAATAGAAAATT36180EiplepsymRNA ------------------------------------------------------------

EpilpesyDNA ACACTACTTGGTGACCTTCCCCAGTCATACAGCATTAGCACTGTGCTATGTCTATATTTG36240EiplepsymRNA ACATCACTT-----------------------------CACTTTGC-------------- 45

*** **** **** ***

EpilpesyDNA TGTACTAGGGACACATTTCCCTTTCCTTGACATTATCAGGACAATTTTTTACTCATTAAC36300EiplepsymRNA ------------------------CTTCGA-------AGG-------------------- 54

* * ** ***


14/28

EpilpesyDNA CTTTATTAGAATCATTCTAGTGATTTACGGAAGAACAAATAGAAAGGGAAAGGGAAAAAC36360EiplepsymRNA ----------------CTGGT--------------------------------------- 59

** **

EpilpesyDNA ATTCCTGTGATCACAGGAAAAGAACCAGAAGAAGGAGAAAGAGGGGGATGATTAAAGAGA36420EiplepsymRNA ----CTGTGCTCA----------------------------------GTG---------- 71

***** *** **

EpilpesyDNA ATAGATGGATAGGTTTTTATAAGAAAACTTTTTTCTGAGGTGGAATGAATGGTGCTAGAA36480EiplepsymRNA ------------------------------TTTTC----GTGG------TGATGCAAG-- 89

***** **** ** *** **

EpilpesyDNA AGGAAAAGGAGGCGTGGGCTTTAGAAAGGAGAAAGGATGTACTGGGGAAGAGATAGAGCT36540EiplepsymRNA --------------TCGGCT---------------------------------------- 95

* ****

EpilpesyDNA ACTGGCACTGTGGGTTGGAGGTTTGGTTGCTCTCCGGAGCAAGCGAGGAGGAAGCAGGCA36600EiplepsymRNA -----------------------------CTCTCC-------------------------101

******

EpilpesyDNA GAAGGGGCAGCCCAGGCAAGAGGAGGGGGCGCATTTTGGAGATGGACACTCACCAGTTTG36660EiplepsymRNA ----------TCCAG--------------------------------------CAGTT--111

**** *****

EpilpesyDNA GTTAGTCATCATTTGGGAGATATCCCCTAGATTGAGCGTCTGAGAGTGTGAATCTCTCGT36720EiplepsymRNA -----------------GGATCCCTCCCA---------TCTCACAGT----ACCTCACAG141

*** * ** * *** * *** * *** *

EpilpesyDNA GTTCTGTTCTAAATGGAAAGATCAATGCCCAGGAATCATTGTTGTTTTTAACCAACATAA36780EiplepsymRNA GT-CTCTTCC-----------------CCCGAGCA-------------------------158

** ** *** *** * *

EpilpesyDNA AGTGTTGTTTAAATATTGAGTGCACCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGGGT36840EiplepsymRNA -------------------GTGCATT----------------------GCTGGAGCGAG-176

***** ** * *** *

EpilpesyDNA GGATCACTGAAGCTCAGGAGTTCAAGACCAGCCTGGCCAACATGGTGAAACCCTGTCTCT36900EiplepsymRNA -GA-----GAAGCTCACGAAT---------------------------------------191

** ******** ** *

EpilpesyDNA ACTAAAAATACAACAATTAGCCGGGTATGGTGGCGGGCACATGTAATCCCAGCTACGGCA36960EiplepsymRNA -------------------------------------------------CAGCTGC----198

***** *


15/28

EpilpesyDNA GGCTAAGGCAGGAAAATCACTTGAACCCGGGAGGCAGAGGTTTCAGTGAGCTGAGGTCAC37020EiplepsymRNA -------------------------------------AGGTCTC----------------205

**** **

EpilpesyDNA ACCACTTCACTCCAGCCTGGGTGACAGAGCGAGACTTTTGTCTCAAGAAATAAAAGTAAA37080EiplepsymRNA --------------------------------------TGTTTTGA-----AAAAGCAG-221

*** * * ***** *

EpilpesyDNA TAAATATGGAGTGGGTGTTGAAGTGAACAGGTTAGGAACTGAAAGGACAATAGCAGGAAT37140EiplepsymRNA -AGATACAGAG-----------------------------------------GCAG----235

* *** *** ****

EpilpesyDNA CTGAGTAGTAGTTCAGAAGAAAAAAAAAGGACCACAAGTCTTTTAGTAGGCTGGAAATGA37200EiplepsymRNA ---------------------AGGAAAAGG---------------GTGGACT--------251

* ****** ** * **

EpilpesyDNA CAAAAGAGACTCATCACTAAGCTTTATCATTAAATGCCTTTGTTTAATTTATCACTACAG37260EiplepsymRNA ------------------------------------CCTATGT-----------------258

*** ***

EpilpesyDNA TTTACATCACCTTTTTTTTTTTTTTTCCAGGAGCCTTGCAAACAACAATCTCCAGACACT37320EiplepsymRNA ------------------------------------------------------------

EpilpesyDNA CCCAAAAGATATTTTCAAAGGCCTGGATTCTTTAACAAATGTGTAAGAGGACCTAAGAAA37380EiplepsymRNA -------------------GACCTG--TTCTT-------------AGAG----CAAGA--278

* **** ***** **** ****

EpilpesyDNA TCACTGAACAATTAATTAATTTGCAGTCATTAACAAGGAAGCCTGGTATTGATTATTATA37440EiplepsymRNA -----------------------CAATCACCA----------------------------287

** *** *

EpilpesyDNA ATTTTTAATTGGCTTTTAAATTAAAATTAGGATTTTTAAATCTAAATTTTAACTGGCCAA37500EiplepsymRNA ----------------------------------------TCTGAATT--------CCAG299

*** **** ***

EpilpesyDNA AAATTTAAATTTACATGGACTAACATTTGAGTCTTCTATGGTATTTATCATTGGGAATTC37560EiplepsymRNA AAGCCC-----------------------------------TGTTCATGGTTGGGGAT--322

** * ** ** ***** **

EpilpesyDNA TGAATACATGGCACCCAGGCATTCCTTTGACAAAGTGTGTGTCAATACGGCAGGGAGCGA37620EiplepsymRNA --------------------ATTTTCTCGAC----TGCATG-------------------339


16/28

*** * *** ** **

EpilpesyDNA TGATAAAGGACTTTGACGGGGTGGGAAGAGACCCGGCTAGAAATTTCAAAATCCCTTTTT37680EiplepsymRNA ---------------------------------------GAA---TCAGAA---------348

*** *** **

EpilpesyDNA TCTCATGAGGTCCAGGAAATAGGGCTACAAAGGAAAAACATAAAGGAGTCTGGGAAACTG37740EiplepsymRNA ---------------------------------AGAAGCA-AAAGGA---TGGGAAA---368

* ** ** ****** *******

EpilpesyDNA ACAGAATAAAGATGAAAGGTTACATCCTTGGGTTGGTCAATCAACAGAGAAATGGAACAG37800EiplepsymRNA ------------------------------------------------------------

EpilpesyDNA GAAGTGGGGGAAGGGAGAAAAGTTTGCCTTTTTTCTCATTAGACTGAACAACAACTCTAA37860EiplepsymRNA ------------------------TGCCTGCATTCCC------CTGAA-AAGAATT----393

***** *** * ***** ** ** *

EpilpesyDNA GCTTAATCCCCAGGAATTTGGCTTAAGCCCCAGGAAGGGAATGAACTTAATTATTTTTGA37920EiplepsymRNA GCTTATTTCCTA------TGTCTC--------------------------TTATCT----417

***** * ** * ** ** **** *

EpilpesyDNA CCCTTTTTCAAACAAAAGAGCTTTCAAACTTTGACTTTTAAGCCTCCGAGTGAAAGATCT37980EiplepsymRNA -----------------GCGCTTTTG----CTGACT-----------GAGGGGAAGA---442

* ***** ***** *** * ****

EpilpesyDNA TTGCAAGGAATTTGTATATTTTGCTGTAAGCAAAGCAAGTAATATATGCCTAAACTTCTC38040EiplepsymRNA --------AACC----------------AGCGAAGC-----------------------C455

** *** **** *

EpilpesyDNA AAAAGCAATTCAGCTTCATTATTTGCCTTCCAGAACATTAGAAAGGTATTTAAATGTCAT38100EiplepsymRNA AAAA-------------------TGCCCTGCCG---------------------TGT---472

**** **** * * * ***

EpilpesyDNA AAGGTGGAAGACAGGAACAAATGAAAGGATATATGAAAACAAAAGCTTTTTTAAAAAATT38160EiplepsymRNA ------------------------------------------------------------

EpilpesyDNA ATTCAGGTACTTGTCTGTAGAATATATATTCAAAACAACTTTTCTCCAATAACAAACAAA38220EiplepsymRNA ------GTACTTGT----------------------------------------ACCAAA486

******** * ****

EpilpesyDNA AAGAAAATCTGAGTCAAGTACTTTCTTCCAAGCCCAGTATTTAACTTCAAATCAGTAGCC38280


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EiplepsymRNA GA----------------------------------------------------------488

*

EpilpesyDNA TAATGAAAAACTTTCTTTGTTCCTTGCAGTATTTCCCCAGCCCCTCCTCCATGTCTATTA38340EiplepsymRNA TAATG-----------------------------------------CTTTATGT------501

***** ** ****

EpilpesyDNA CCTCAATTCCTGAATGATATGGTTTAATTCCAGGAGAATGCCCAAATCAGGATTCTTCCA38400EiplepsymRNA ---------------------------------GAGAATGCCAGATCCA------TTCCA522

********* * ** *****

EpilpesyDNA AGAGAGTCCTGGACAGACCATAGTTATCCTCTCTGGTTTACAGTAGCCTGAAAGGTTGCC38460EiplepsymRNA -------------CGCACCGT-----TCCTC-CTGAT-----------------GTTATC546

* *** * ***** *** * *** *

EpilpesyDNA ACTCATTAGTGTGGGTCAGAGTTCTCTTGGGAGACTAGGTCAGTTCTGGGAGTGTCTTGG38520EiplepsymRNA --TCATTA--------------TCCTTTGTGAGA----------TCTGG-----------569

****** ** *** **** *****

EpilpesyDNA AAGTTAGAACACACTCCATGGGTGACGTGGGATGTAGCTCATTGGGGGTCCTTTACCCCA38580EiplepsymRNA --------------------------------------------------TTTTAC----575

*****

EpilpesyDNA TTTTTGTGTCAGTCTATACCCTACACTAGTGAAAGACAAAACAAAAAAATATTGAAATTG38640EiplepsymRNA ----------------------------------------------------TGAAAT--581

******

EpilpesyDNA GCTCAGTCTCTCATGGGAATCCCAAGATGGGTTTAGCCTTTTGGACCTACTCTAATATGC38700EiplepsymRNA -CTCAG------AAGGGAGTT-----------------TTTT------------------599

***** * **** * ****

EpilpesyDNA CCAAATCAAGAATTATCTTAGAAGTACAAGGATCCATGCCAACTTGCCTTTTAGTGGATT38760EiplepsymRNA -------------------------------ATTCACGCCA--TCGC-------TGCAGC619

** ** **** * ** ** *

EpilpesyDNA TCTTGGCTTTCTTGAAAGTATCCTCTAAAAAACATTTTTAAATGTTTGGGCGTTTAAAAA38820EiplepsymRNA TCTTG-------------------------------------------------------624

*****

EpilpesyDNA TTATTTATGTGTGGTGTGAAGAGTAGGCAGCACCTATCTTAAGAATTCTGTGTGACCAGG38880EiplepsymRNA TTATTCAC---------------------------ATC----------------------635

***** * ***


18/28

EpilpesyDNA AAAGGAGGTGGAATTCCTGAACAGAAGCAATGCAAATACACAGAGAACTTGGTGAGTTGG38940EiplepsymRNA ----------GAACTCCT------------------------------TTGATG------649

*** **** *** **

EpilpesyDNA GGTCATATGTGGATATGTAAATGGTCTATGCTGTATAACTTATTACAGGCATGAGCGATT39000EiplepsymRNA ---------------------TGATCAGTG--------------------ATGA------662

** ** ** ****

EpilpesyDNA GTATGCCTGTGTTAACTCTGCTGTGTCAAAGTCATTTCCTATTTAAACTGAATTTGTAGA39060EiplepsymRNA ------------------TGCT-------------------TTTA--------TTG----673

**** **** ***

EpilpesyDNA CCACGGAAGAGGATCAGGATTAATTATGTCTGTGAGGAAGAAGAAAAGCAAATAGCTCAC39120EiplepsymRNA ---------------------------GTCT-----------------------------677

****

EpilpesyDNA TTGATTAAATACATTACAATAATCACTACATTCTGTCCTTTAGACCTGTGCTGTCCAATA39180EiplepsymRNA -----------------------------------------------------TCCA---681

****

EpilpesyDNA GGGTAGCCACCAGACCTTATGGTCACTGAGCACCTAAAATGTGCTCCTAGTACAACTGAG39240EiplepsymRNA ------------------------------CATCTAGAGT--------------------691

** *** * *

EpilpesyDNA AGACTGAATTTTAAATTTTACTTAATTTTTTAACAGTTAAATTTAAATTTAAAAGCTGAT39300EiplepsymRNA ------------------------ATTTATTCATAG--------------AAAA------707

**** ** * ** ****

EpilpesyDNA TCTCAGCTCAATTATTGGAAAATGTTAAGTACGCTTGGAATAATTTGGGTATATACACCT39360EiplepsymRNA ---CAAC-------------AACATCAAGTC-----------------------------722

** * ** * ****

EpilpesyDNA ATTTTTTTCAATTATGAATTTTATGACATCTAAATATAGATCACCTATTTCTGGTAAAAT39420EiplepsymRNA ----------------AATTTCAAGACAT-------------AC---TTTCCGG------744

***** * ***** ** **** **

EpilpesyDNA TTAGCATCTGAATTGAGATATATTGTAGGTATAAAATACACACTGGACTTCAAAGACTTA39480EiplepsymRNA --------------------------------------------GGACT-----------749

*****

EpilpesyDNA GTATAAAAAAGGAATGTAAAATATCTCAATAATGTTTATATTGATGATGTGTCAAAATGA39540


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EiplepsymRNA -------AAAG-------------------------------------------------753

****

EpilpesyDNA TAATCTTTTGTATGTATTGGGTTAAATAAAACATATTATTAAAATGAATTATACCTGCTT39600EiplepsymRNA -----------------------------------TCATTAA------------------760

* *****

EpilpesyDNA CTTTTTACTTTTTTAATGTGGCTATAGAAAATTTTAAATTACAATTACGGTTCATATACT39660EiplepsymRNA ---TTCACTT----------------GAGCCTTGCAAACAACAATC----TCCAGACACT797

** **** ** ** *** ***** * ** * ***

EpilpesyDNA GTTTCTATTGACAGCACAGCCCTAGACTAAGCCGCTTTGGAATTCAAGAGGGAGTAAGTG39720EiplepsymRNA ------------------------------------------CCCAAAAGATA-------808

*** ** *

EpilpesyDNA ATGAGGTTCCATTGACTGGGTAGTCTTCAAGTGTGCATGGTGCTAACTCTCTGAGCCCAA39780EiplepsymRNA -----------------------TTTTCAA------------------------------815

* *****

EpilpesyDNA AGTGAATGAGTGGTCAGTCAGGTTCCAGGCAGGTTATAGGGCAGGATGCAACGCCGGGTA39840EiplepsymRNA -------------------------------------AGGCCTGGAT-------------825

*** * ****

EpilpesyDNA AGGTCATTCTGCACATGTTAATTGTTGATGTAGAACTCTTTCCTGCGTGGGTAGGGCCCT39900EiplepsymRNA ------------------------------------TCTTT-------------------830

*****

EpilpesyDNA TGTACAGCAAAAGCAGCTGAAGTTTGTCTTTCAGGGACCTGAGGGGTAATTCATTTAATT39960EiplepsymRNA -----AACAAA-------------TGT-------GGACCTGAGGGGTAATTCATTTAATT865

* **** *** **************************

EpilpesyDNA GTGACTGTAAACTGAAATGGCTAGTGGAATGGCTTGGCCACACCAATGCAACTGTTGAAG40020EiplepsymRNA GTGACTGTAAACTGAAATGGCTAGTGGAATGGCTTGGCCACACCAATGCAACTGTTGAAG925

************************************************************

EpilpesyDNA ACATCTACTGCGAAGGCCCCCCAGAATACAAGAAGCGCAAAATCAATAGTCTCTCCTCGA40080EiplepsymRNA ACATCTACTGCGAAGGCCCCCCAGAATACAAGAAGCGCAAAATCAATAGTCTCTCCTCGA985

************************************************************

EpilpesyDNA AGGATTTCGATTGCATCATTACAGGTAATGTACTCATCATCATTCCACCTCAAAAAATTA40140EiplepsymRNA AGGATTTCGATTGCATCATTACAG------------------------------------1009

************************


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EpilpesyDNA TCTAGCCAAGGAAAGAGGTATTAGCTCACAGTTACTTATTATTTCCTATTTTTGCAGAAT40380EiplepsymRNA ---------------------------------------------------------AAT1012

***

EpilpesyDNA TTGCAAAGTCTCAAGACCTGCCTTATCAATCATTGTCCATAGACACTTTTTCTTATTTGA40440EiplepsymRNA TTGCAAAGTCTCAAGACCTGCCTTATCAATCATTGTCCATAGACACTTTTTCTTATTTGA1072

************************************************************

EpilpesyDNA ATGATGAGTATGTAGTCATCGCTCAGCCTTTTACTGGAAAATGCATTTTCCTTGAATGGG40500EiplepsymRNA ATGATGAGTATGTAGTCATCGCTCAGCCTTTTACTGGAAAATGCATTTTCCTTGAATGGG1132

************************************************************

EpilpesyDNA ACCATGTGGAAAAGACCTTCCGGAATTATGACAACATTACAGGTATGAAAAGCCTAATGA40560EiplepsymRNA ACCATGTGGAAAAGACCTTCCGGAATTATGACAACATTACAGG-----------------1175

*******************************************

EpilpesyDNA TATTTTGAGTGGTAATTTAAACTGCTTCAGCCAAGGGCAACAAGGAAAGATGAGTGGTAT40620EiplepsymRNA ------------------------------------------------------------

EpilpesyDNA CACATCCACTGTAGTATGCAAGCCTATAGTCATTGAAACTCAGCTCTATGTTATTGTGGC44220EiplepsymRNA CACATCCACTGTAGTATGCAAGCCTATAGTCATTGAAACTCAGCTCTATGTTATTGTGGC1235

************************************************************

EpilpesyDNA CCAGCTGTTTGGTGGCTCTCACATCTATAAGCGAGACAGTTTTGCAAATAAATTCATAAA44280EiplepsymRNA CCAGCTGTTTGGTGGCTCTCACATCTATAAGCGAGACAGTTTTGCAAATAAATTCATAAA1295

************************************************************

EpilpesyDNA AATCCAGGATATTGAAATTCTCAAAATCCGAAAACCCAATGACATTGAAACATTCAAGAT44340EiplepsymRNA AATCCAGGATATTGAAATTCTCAAAATCCGAAAACCCAATGACATTGAAACATTCAAGAT1355

************************************************************

EpilpesyDNA TGAAAACAACTGGTACTTTGTTGTTGCTGACAGTTCAAAAGCTGGTTTTACTACCATTTA44400EiplepsymRNA TGAAAACAACTGGTACTTTGTTGTTGCTGACAGTTCAAAAGCTGGTTTTACTACCATTTA1415

************************************************************

EpilpesyDNA CAAATGGAACGGAAACGGATTCTACTCCCATCAATCCTTACACGCGTGGTACAGGGACAC44460EiplepsymRNA CAAATGGAACGGAAACGGATTCTACTCCCATCAATCCTTACACGCGTGGTACAGGGACAC1475

************************************************************

EpilpesyDNA TGATGTGGAATATCTAGAAATAGTCAGAACACCTCAGACACTCAGAACGCCTCATTTAAT44520EiplepsymRNA TGATGTGGAATATCTAGAAATAGTCAGAACACCTCAGACACTCAGAACGCCTCATTTAAT1535


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************************************************************

EpilpesyDNA TCTGTCTAGTAGTTCCCAGCGTCCTGTAATTTATCAGTGGAACAAAGCAACACAATTATT44580EiplepsymRNA TCTGTCTAGTAGTTCCCAGCGTCCTGTAATTTATCAGTGGAACAAAGCAACACAATTATT1595

************************************************************

EpilpesyDNA CACTAACCAAACTGACATTCCTAACATGGAGGATGTGTACGCAGTGAAGCACTTCTCAGT44640EiplepsymRNA CACTAACCAAACTGACATTCCTAACATGGAGGATGTGTACGCAGTGAAGCACTTCTCAGT1655

************************************************************

EpilpesyDNA GAAAGGGGACGTGTACATTTGCTTGACAAGATTCATTGGTGATTCCAAAGTCATGAAATG44700EiplepsymRNA GAAAGGGGACGTGTACATTTGCTTGACAAGATTCATTGGTGATTCCAAAGTCATGAAATG1715

************************************************************

EpilpesyDNA GGGAGGCTCCTCGTTCCAGGATATTCAGAGGATGCCATCGCGAGGATCCATGGTGTTCCA44760EiplepsymRNA GGGAGGCTCCTCGTTCCAGGATATTCAGAGGATGCCATCGCGAGGATCCATGGTGTTCCA1775

************************************************************

EpilpesyDNA GCCTCTTCAAATAAATAATTACCAATATGCAATTCTTGGAAGTGATTACTCCTTTACTCA44820EiplepsymRNA GCCTCTTCAAATAAATAATTACCAATATGCAATTCTTGGAAGTGATTACTCCTTTACTCA1835

************************************************************

EpilpesyDNA AGTGTATAACTGGGATGCAGAGAAAGCCAAATTTGTGAAATTTCAGGAATTAAATGTTCA44880EiplepsymRNA AGTGTATAACTGGGATGCAGAGAAAGCCAAATTTGTGAAATTTCAGGAATTAAATGTTCA1895

************************************************************

EpilpesyDNA GGCACCAAGATCATTCACACATGTGTCCATTAATAAGCGTAATTTTCTTTTTGCTTCCAG44940EiplepsymRNA GGCACCAAGATCATTCACACATGTGTCCATTAATAAGCGTAATTTTCTTTTTGCTTCCAG1955

************************************************************

EpilpesyDNA TTTTAAGGGAAATACACAGATTTACAAACATGTCATAGTTGACTTAAGCGCATGAGACAC45000EiplepsymRNA TTTTAAGGGAAATACACAGATTTACAAACATGTCATAGTTGACTTAAGCGCATGAGACAC2015

************************************************************

EpilpesyDNA CAAATTCTGTGGCTGCCATCAGAAATTTTCTACAGTACATGACCCGGATGAACTCAATGC45060EiplepsymRNA CAAATTCTGTGGCTGCCATCAGAAATTTTCTACAGTACATGACCCGGATGAACTCAATGC2075

************************************************************

EpilpesyDNA ATGATGACTCTTCTTATCACACTTGCAAATGAATGCCTTTCAAACATTGAGACTGCTAGA45120EiplepsymRNA ATGATGACTCTTCTTATCACACTTGCAAATGAATGCCTTTCAAACATTGAGACTGCTAGA2135

************************************************************


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EpilpesyDNA ACCAAGCACTACCAGTATCTCCATCCTTAACTGTCCAGTCCAGTGATGTGGGAAGTTACC45180EiplepsymRNA ACCAAGCACTACCAGTATCTCCATCCTTAACTGTCCAGTCCAGTGATGTGGGAAGTTACC2195

************************************************************

EpilpesyDNA TTTTATAAGACAAAATTTAATTGTGTAACTGTTCTTTGCAGTGAAGATGTGTAAATAAGC45240EiplepsymRNA TTTTATAAGACAAAATTTAATTGTGTAACTGTTCTTTGCAGTGAAGATGTGTAAATAAGC2255

************************************************************

EpilpesyDNA GTTTAATGGTATCTGTTACTCCAAAAAGAAATATTAATATGTACTTTTCCATTTATTTAT45300EiplepsymRNA GTTTAATGGTATCTGTTACTCCAAAAAGAAATATTAATATGTACTTTTCCATTTATTTAT2315

************************************************************

EpilpesyDNA TCATGTGTACAGAAACAACTGCCAAATAAAATGTTTACATTTTCTTTCATATCCCAGAGG45360EiplepsymRNA TCATGTGTACAGAAACAACTGCCAAATAAAATGTTTACATTTTCTTTCATA---------2366

***************************************************

EpilpesyDNA TAATTATTTACAGGAGCTGTTTCATTCTTGTTGTTGGTATGTTGAAGAAATAGTTTTATA45420EiplepsymRNA ------------------------------------------------------------

Con la herramienta expasy toolse realiza una prediccin de la transcripcin con base al mRNA,

debido a la naturaleza de cdigo gentico degenerado se presentan 6 frames, el frame elegido es

aquel con menor nmero de stop codons.

La secuencia de aminocidos es corrida en Blastprotein con el fin de identificar a que

protena pertenece.


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La protena con mxima identidad es NP_005088 Leucine-rich glioma-inactivated protein 1

coincidiendo con lo reportado en ncbi para el gen ILGI1.

Seguidamente se realiza un traduccin reversa partiendo de la proteina NP_005088 .1, se

obtienen dos posible secuencias.


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En la herramienta clustalw se realiza un alineamiento entre las dos secuencias obtenidas

en la traduccin reversa y la secuencia de mRNA correspondiente a LGI1.

Entre la secuencia Reversa1 y la secuencia mRNA se logra el mayor score de alineamiento(74.0), seguidamente se corre en Blast-nucleotide la secuencia Reversa1 y se aprecia que

evidentemente coincide con la secuencia del ARN mensajero del gen LGI1.


25/28

Con la herramienta expasy-tool calculamos el punto isoelctrico y el peso molecular de la

protena.

Con la herramienta REBsites identificamos las enzimas de restriccin que menor nmero

de fragmentos produce en la secuencia de DNA del gen LGI1


26/28

Para el diseo de primers se tiene en cuenta la regin del mRNA correspondiente a la

secuencia codificante (CDS) que comprende las regiones entre los nucletidos 337 y 2010.

Los primers con mayor porcentaje de GC, es decir los ms estables son mostrados en la

siguiente imagen.


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Referencias

[1] Mutant LGI1 inhibits seizure-induced trafficking of Kv4.2 potassium channels. Smith SE,

Xu L, Kasten MR, Anderson MP. J Neurochem. 2012 Feb;120(4):611-21. doi:

10.1111/j.1471-4159.2011.07605.x.

[2] Familial temporal lobe epilepsy with psychic auras associated with a novel LGI1

mutation.Striano P, Busolin G, Santulli L, Leonardi E, Coppola A, Vitiello L, Rigon L,

Michelucci R, Tosatto SC, Striano S, Nobile C. Neurology. 2011 Mar 29;76(13):1173-6.

[3] Electroclinical characterization of epileptic seizures in leucine-rich, glioma-inactivated

1-deficient mice. Chabrol E, Navarro V, Provenzano G, Cohen I, Dinocourt C, Rivaud-

Pchoux S, Fricker D, Baulac M, Miles R, Leguern E, Baulac S. Brain. 2010 Sep;133(9):2749-

62. Epub 2010 Jul 21.

[4] The leading edge of epilepsy research. Ikeda A. Rinsho Shinkeigaku. 2011

Nov;51(11):993-6.

[5] Epilepsy gene LGI1 regulates postnatal developmental remodeling of retinogeniculate

synapses.Zhou YD, Zhang D, Ozkaynak E, Wang X, Kasper EM, Leguern E, Baulac S,

Anderson MP. J Neurosci. 2012 Jan 18;32(3):903-10.

[6] Low penetrance and effect on protein secretion of LGI1 mutations causing autosomal

dominant lateral temporal epilepsy. Di Bonaventura C, Operto FF, Busolin G, Egeo G,

D'Aniello A, Vitello L, Smaniotto G, Furlan S, Diani E, Michelucci R, Giallonardo AT, Coppola

G, Nobile C. Epilepsia. 2011 Jul;52(7):1258-64. doi: 10.1111/j.1528-1167.2011.03071.x.

Epub 2011 Apr 19.

[7] Autoimmune epilepsies. Irani SR, Bien CG, Lang B. Curr Opin Neurol. 2011

Apr;24(2):146-53. Review.


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[8] The temporal and spatial expression pattern of the LGI1 epilepsy predisposition gene

during mouse embryonic cranial development. Silva J, Wang G, Cowell JK. BMC Neurosci.

2011 May 13;12:43.

[9] LGI2 truncation causes a remitting focal epilepsy in dogs. Seppl EH, Jokinen TS,

Fukata M, Fukata Y, Webster MT, Karlsson EK, Kilpinen SK, Steffen F, Dietschi E, Leeb T,

Eklund R, Zhao X, Rilstone JJ, Lindblad-Toh K, Minassian BA, Lohi H.PLoS Genet. 2011

Jul;7(7):e1002194. Epub 2011 Jul 28.

[10] Similarity of molecular phenotype between known epilepsy gene LGI1 and disease

candidate gene LGI2. Limviphuvadh V, Chua LL, Rahim RA, Eisenhaber F, Maurer-Stroh S,

Adhikari S. BMC Biochem. 2010 Sep 24;11:39.

[2]bioinformatica componente genético de epilepsia en lóbulo temporal

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