Universidade Federal do Maranhão - UFMA

Curso de Licenciatura em Ciências Naturais

Campus de Codó
Genética e Evolução I

Os genes são feitos de DNA

A estrutura do DNA
Genes e informação biológica

Msc. Jefferson Almeida Rocha

Créditos Giovanny Rebouças

Gregor Mendel (1822 – 1884)

Genética e Evolução I
Gregor Mendel (1822 – 1884)
 Cepas de Pneumococcus

Frederick Griffith
1881 – 1941

Genética e Evolução I
Griffith (1928): Transformação Bacteriana

1º - IS vivas 3º - IS mortas por aquecimento

2º - IIR vivas 4º - IS mortas + IIR vivas

Genética e Evolução I
Griffith (1928): Transformação Bacteriana

4º - IS mortas + IIR vivas

Genética e Evolução I
Avery, MacLeod e McCarty (1944)
Hershey e Chase (1952)

Genética e Evolução I
Hershey e Chase (1952)
 Proporções de Bases de Chargaff

Erwin Chargaff
1905 – 2002

Genética e Evolução I
DNA: Molécula de Estrutura Regular

Rosalind Franklin
1920 – 1958

Maurice Wilkins
1916 – 2004

1962
James Watson e Francis Crick (1953) 1962

Genética e Evolução I
James Watson e Francis Crick (1953)

Genética e Evolução I
Componentes dos Nucleotídeos

Nucleotídeo Pirimidinas

Base
nitrogenada

Grupo
fosfato Citosina Uracila Timina
Açucar de 5 (C) (U) (T)
carbonos
Purinas

Ribose Desoxirribose

Adenina Guanina
(A) (G)

Genética e Evolução I
Ácido Fosfórico e Polinucleotídeos

γ β α

5’

Genética e Evolução I
Polinucleotídeos

Genética e Evolução I
Polinucleotídeos

410 = 1.048.576 sequências

A – T – A – G – A – A – C – A – G – G

A – A – A – G – A – A – C – A – G – G

A – T – A – T – A – A – C – A – G – G

A – T – A – C – A – A – C – A – G – G

A – T – A – G – A – G – C – A – G – G

Genética e Evolução I
DNA vs. RNA
Complementaridade de Bases

Genética e Evolução I
Genes: Segmentos de DNA

3’ Gene A 5’

5’ 3’

Filamento molde Gene A

3’ 5’

5’ 3’

Filamento complementar

Genética e Evolução I
Cariótipo Humano

Genética e Evolução I
Cromossomos: DNA + Proteínas
Genes: Segmentos de DNA

Gene I Gene II
3’ 5’

5’ 3’
Gene III

Genética e Evolução I
Genes: Segmentos de DNA

Gene I Gene II
3’ 5’

5’ 3’
Gene III

Genética e Evolução I
Genes: Segmentos de DNA

Gene I

3’ 5’

5’ 3’

Gene I

5’ 3’

Genética e Evolução I
Genes nos Bancos de Dados

Genética e Evolução I
 Genes Podem Ocorrer em Grupos

Óperon lac de E. Coli

Z Y A
5’ 3’

Genética e Evolução I
 Genes Podem Ocorrer em Grupos

Famílias multigênicas simples

 rRNA 5S de Drosophila

Genes (120 pb)

5’ 3’

Regiões intergênicas (250 pb)

Genética e Evolução I
Genes Podem Ocorrer em Grupos

Genética e Evolução I
 Genes Podem Ocorrer em Grupos

Cromossomo 11 (11p15) – Cluster β-símile

ε Gγ Aγ ψβ δ β
5’ 3’

60 kb

Cromossomo 16 (16p13) – Cluster α-símile

ζ ψζ ψα2 ψα1 α2 α1 θ
5’ 3’

30 kb

Genética e Evolução I
Genes Podem Ocorrer em Grupos

A
5’ 3’

A A
5’ 3’

Aα Aβ
5’ 3’

Genética e Evolução I
Recomposição de Éxons

Gene A Gene B

AI AII BI BII
5’ 3’

AI BII
5’ 3’

Genética e Evolução I
Dogma Central da Biologia Molecular
Histonas

Genética e Evolução I
Histonas

Genética e Evolução I
Solenóide, fibra de 30 nm

Genética e Evolução I
Fibras de 300 nm e 700 nm

Genética e Evolução I
O arcabouço cromossômico

Genética e Evolução I
Topoisomerases
Modificações das Histonas

Genética e Evolução I
Modificações das Histonas

Genética e Evolução I
TAAAGGTATTTTGGGGGTGGGCAGGGAGAAGACAGAGAGAGAAAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGAGACAGGCTGGCCTCCCAGAGCGAACGGAAGAGGACTGAGGACTGAACCCAGGGAGCCCCTAGCACTGGCCATTTGGCAGGAGGCGAGGAAGGGCGAGGGCACCGCGGCTTCCCCCCA
AGCCGAGCAGTGGCCACAGCCTGAAGGTGCCACGGGGCGGCTCTGGGATCTTCTTGGCTTTTCTAGGCTCTGGGCTCGGCGAGGCTGCCGGGTTAGCGGGAACCGGCAGGTTGCTGGAGAAAGGAGAGGGACAAAGGCCTGGAAGTGGGGGAGGCACCAGGGACTGGGCGGCCGGGATGGGAGCCTTTGCCTTTAGG
GCTCACTGGACCCGTTTGCCAGCTCCGCGGACAAGGGATCCCACCTTCCCAGGGTCTGCAAAAAGAGAGACGTTTGGGGCACTACAAAGTGACGCAGGTGTCTGCCAAGACTTTCCTTCTCCAAAAAATGCCAGTCTTCACCCTTTCCAGCGCGCCGGCGCTGCGCCTCTGCTTGACCGGGGAAAGAGAGAGTTTGG
GAGTTGGCAAGAAAGGACAGCACAGAAACTTGCACCCTCCGAGGACTGGGAGTCCCGAGTCCAGCTTAGGGGGAGTGGGGGCGCGACCCCCAACCCAGAAACCTTCACTTGACCGCTCAAGTTCGCGGCAGCAGGGCGGGCCGCGCCGAATCTCGGCGTGCGCGGAGCGGGGAGATGCAGGCGAGCGCCAGAGCCCG
GGCTCGGGGGCCCTGCGCCGGGGAGAGGAGCCGGGACCCACCGGCGGAGCCGAAAACAAGTGTATTCATATTCAAACAAACGGACCAATTGCACCAGGCGGGGAGAGGGAGCATCCAATCGGCTGGCGCGAGGCCCCGGCGCTGCTTTGCATAAAGCAATATTTTGTGTGAGAGCGAGCGGTGCATTTGCATGTTGC
GGAGTGATTAGTGGGTTTGAAAAGGGAACCGTGGCTCGGCCTCATTTCCCGCTCTGGTTCAGGCGCAGGAGGAAGTGTTTTGCTGGAGGATGATGACAGAGGTCAGGCTTCGCTAATGGGCCAGTGAGGAGCGGTGGAGGCGAGGCCGGGCGCCGGCACACACACATTAACACACTTGAGCCATCACCAATCAGCAT
AGGTGTGCTGGCTGCAGCCACTTCCCTCACCCACACTCTTTATCTCTCACTCTCCAGCCGCTGACAGCCCATTTTATTGTCAATCTCTGTCTCCTTCCCAGGAATCTGAGAATTGCTCTCACACACCAACCCAGCAACATCCGTGGAGAAAACTCTCACCAGCAACTCCTTTAAAACACCGTCATTTCAAACCATTG
TGGTCTTCAAGCAACAACAGCAGCACAAAAAACCCCAACCAAACAAAACTCTTGACAGAAGCTGTGACAACCAGAAAGGATGCCTCATAAAGGTGAGTCCGCTTCTTTCTTCTCGCTTTATTTTTATTGCAATATTCAGACAGGTCTCCCCCTTCCTCCCCCCTTCCTTCCTCCCCTCTCGCCGGTCCCCTCCCCCA
CTGCTACGCCGGGAGAGTTGGGCCGGAGAAGTTTCCACGCAGGAGCCCAAACTTTCTACTTCCAGCGAAAGCCCGCGTCGGAGGGCGACTGCCGGCGAGCGGGAGCGGCGCAGGGCTCGGGGCGGGCGGCCAGCTCAGCCCCAGCGCCAGCGCCAGCGCCAGCGCGGGCTGAGCTCGCGGGAAGAAGGGAGACTCCA
GGCGCGACAGCAGCCGCGGCTCCTAGCCCCAGCGTCGCCCAATGCTCCCGACCCGCGGGAAAAGACGAAGAGGCTCTGTGGTGCCCAAGGCCCTGGAACGGCCGCAGAGAGCAACCGCTGCCGGCTGCTTTGTCCAGCCCGAGGCCCAGCGAACGCGCAGAGAGCGGGCGCTCCGAGGACTCGCCGAGGGAGCGCCG
AGGGAACCTGCTCGCCGCGTCTCCGCCCGCCCGCCGGCCCTCGGGCTTTGTGCCGCACTGGGCTCCGGCGCAGAAGAGTCAGCCGGCACTCGAGCGCCGAGGGGGGCACCGCGCCCGCCACCAGCCCGAGTGGAGTCAGTCGGCAAGGCAGCCGCACGCTGGAGGTAGAGGGAAGAGCGAGCTAGCGCGAGCCGGGA
AGGAAGCCACCAGGCCAAGGCGGTGGAACGCGCGCTCCGAGGGAGCTCAGAGCCGAGCGGGAGGACTGTCAGCTTCCACCCAGCCCCCGGGCTCTTGCCCCCAACTCCACTGGAGCGCTGAGCTCGGAACTTGAAAACTCTCTGCTCCCCAGGCTTCCCCCGACTCTCATCTCCCTTGCCTTGCGGAGGCTGGGGCT
CTTCCCTGTTCTCCGGCCCCCTGCGCTTGGTGGGTATTTTTCCTTGTTTTCCTCTGATCCAGTCTCACCAGGTGTTGGGATTTCAGCAAGTTTTGAGGTGCAGAGTTGGTTTGCTTTTTTGTTTGTTTTACTCCGAATCCCCTTATGTTTTTCTTGGTAAGGCCTTGAAAATAAATCTGTATGAAAGCATTGGCCTT
CCCCCTCGTCTGATCACTTCTTCTCCCGGCTAATTAGTCGGAGTAATTTGAGAGCTTTCGATTCTAAGATCCCAGGAGGAAAAGTGTCTTTTCAAAGTTCATAAAGTTGTTGCCTCTTTCCTTGTGCAGATTTTCTCAGTCTCCCTGCGCCATAATAGCCCTGAATTTTAGCAAGTGTAATTGGGGGAAATGGAGTT
GAATTTCAAGTGGAAATGCTTTCTTTTTCGAGTGCTAAAACCTGGCTCTTCATTCATGAGCGATTTCTAGAAAGTTTAAAAACAAAGTGAACGTGGTTTCTTTCTTTCTTCCTTTTTATTTTTCTTATACTCTCCCAAGCTCCCTAAGCCATTCTGGACGTTTAACTCGAACTTGGGAAGGTTTTAGAAGGGGCTGG
GAGCAGAAAATGAAATGAAAGGCAAAGAGCTTGAGCCTGGCGAGTTTACTGAAGAGAAATAATAGTTGTTGCGGTTGACATTACATTTTTTATAGCCAGTGACCTTTGCAAAAGCGTGAAGGCAGTTTGATTAGTTGTTATCTTATTTGGCCCTAGAGAGTAAAACTTTGTCATCATAATTGCTAATTACTCTTTTG
GCTGGGGGCGGGAGGACCGAGAGCTCTCCCCTTTACCTCAGTTAAAGAGTTTGGGGATGGAATTTGAGAATTAAGTAATTAAAAAAAGAACAGCATTTGAAAACTGAGGCTTGTGTTGGGGACAGAGAGGTGGGGGCAGTGACCACTCTCTTGTGGTCCAAGGCTGGGGCGACTCCAAAATGTCTGGAGACTCCTTC
GTTCAGGATGTGGTTCTATGGCCCCAGCGAGGCCGTACAGAGCCTCGGGCTGAGCTGGGGGGCTGAGGCTGCAGTTGGGGGTCTGACCTCTCCGGTGCACAGGACTGCTTCCGGGTGTCGATGTGCCCCACTTCCCGGGTTGCTTCTGCACTTAGTGTTCACGTTTACTTAAGTAATTAGATAGCTTCTTAGCGAGA
GGGAAGTGGGAATGGAGCAGAACTGGAATTTGAAATACTACCACCTTCCCAGCTGCTTCGAAAACTAATCAACGAGGCCTCTTTGTGCTCAGCTACTGAATTTAAAAAAAAATGGTATCAAGAAGTTACAAGCCAGGATGGGAGCATTCTGTTGTGATTGTGCACAGCGTGGGTTACAAAGTGGAGTTCTGGAAGTT
TTACCCCTCCTAGGGGAATTCCATTCCCCATCTCCCCACCTACTACTCCTTTGCAGCTTCAGGGTCCTGCATTTGTTGGGGTGGGGTATTTTGCATTAGAGTTGGAGATTTTGCCTATCCAGGGCATGGCTATGGGTGCCGGGACTGAGAGACAGGAAGGAAGCATTGGAGAGCCAACCTAGATAAGGGTAACTAGT
AACCCTCTGCTGTGGCCAGTATTTACCCAATGCTGAGAAAAAGTCCTCATTTTCGGTTTATTTTTATGGATTTAAGCTGTCTACCAAGTAGTTAAAAAGTAGACCAGGAATGGCCTTGTAGAGTAAAATGTGCTTCTTGAAATTCTTTGCTTGCAGGCAGGCAGATCAATAATCACCATAGGTAAAACAGAAAAAAT
AATGCATTTAAAAAAAAACAGAGAGAAATGATGCTGTGACTGTTTTGTTATTTTACCTCTTTTTGGGGGGCAGACCTCTTGAATGGGCTCTTTATTGTAACTCTCTCTTCCCAATTGAGCTCCCCACGGTGCCGTTGTATCTTTTTACAGCCCCTAACAACTCACACCAGTAACACAATTACCTCCAGATATTTACA
ACAAGAAATTACTTTTCTATTTTCTCCACTCACCCAAAAGACTTTTTTTTTTTTTCCTTTGGGAAAGGTAGGGAGGTGTTCGTACGGGAGCAGCCTCGGGGACCCCTGCACTGGGTCAGGGCTTATGAAGCTAGAAGCGTCCCTCTGTTCCCTTTGTGAGTTGGTGGGTTGTTGGTACATTTGGTTGGAAGCTGTGT
TGCTGGTTAGGGAGACTCGGTTTTGCTCCTTGGGTTCGAGGAAAGCTGGAGAATAGAAGCCATTGTTTGCCGTCTGTCGGCTTTGTCGACCACGCTCACCCCCTCCTGTTCGTACTTTTTAAAGCAGTGAGGCGAGGTAGACAGGGTGTGTCACAGTACAGTTAAAGGGGTGAAGATCTAAACGCCAAAAGAGAAGT
TAATCACAATAAGTGAGGTTTGGGATAAAAAGTTGGGCTTGCCCCTTTCAAAGTCCCAGAAAGCTGGGAGGTAGATGGAGAGGGGGCCATTGGGAAGTTTTTTTGGTGTAGGGAGAGGAGTAGAAGATAAAGGGTAAGCAGAGTGTTGGGTTCTGGGGGTCTTGTGAAGTTCCTTAAGGAAGGAGGGAGTGTGGCCC
TGCAGCCCTCCCAAACTGCTCCAGCCTATGCTCTCCGGCACCAGGAAGTTCCAAGGTTCCCTTCCCCTGGTCTCCAAACTTCAGGTATTCCTCTCCCCTCACACCCCTTCAACCTCAGCTCTTGGCCTCTACTCCTTACTCCACTGTTCCTCCTGTTTCCCCCTTCCCCTTTTCCTGGTTCTTTATATTTTTGCAAA
GTGGGATCCGAACTTGCTAGATTTTCCAATTCTCCCAAGCCAGACCAGAGCAGCCTCTTTTAAAGGATGGAGACTTCTGTGGCAGATGCCGCTGAAAATGTGGGTGTAATGCTGGGACTTAGAGTTTGATGACAGTTTGACTGAGCCCTAGATGCATGTGTTTTTCCTGAGAGTGAGGCTCAGAGAGCCCATGGACG
TATGCTGTTGAACCACAGCTTGATATACCTTTTTCTCCTTCTGTTTTGTCTTAGGGGGAAGACTTTAACTAGGGGCGCGCAGATGTGTGAGGCCTTTTATTGTGAGAGTGGACAGACATCCGAGATTTCAGGCAAGTTCTGTGGTGGCTGCTTTGGGCTCAAAACCCACAAACAGTCAAAACAAACTATTTCAGTAT
GCTTCTTCACTATAGTTCAGATAGAAGAAAATAAATCAAAATTGGGGCATCGCTTCTACTGATTAAAGGGTTAACTGCTAAAGAATGTAGGGGAAACAGATTGGGGATATTCCAGTACTTTGTTTCAAGCCCCAAAGGGTAGATTTTGTATGCACTGCAGGGCAGAGCTGAGTGACCCTCAGATCGCCCCAAGAGGT
TGAGTGGATCAATTCCTAAAGAACGGAGATTCTCCTGTCCTAGCCCCAGGTCCACCTCGGTTGGGAGTTCAGGCCTACCTGATGCAGCTGCCCGAGGATTAACTCCTATTTTCTTGCTAACAGAGCCCCATATTCGAGCCCCGTGGAATCCCGCGGCCCCCAGCCAGAGCCAGCATGCAGAACAGTAAGTGCCTCTG
GTCTTTCTGGGACTTCGGGCTCGGGGTGCGCGGACCCGAGGGTCAGGGGAGGACACAGGGACTCGCGACGCCCGCGCTGGCCCGGCCGCCGACCGACTGAGGCCCGGGGACCTGCGGCGGCTGCTCCCCGCTCCGCGCCCGGCAGCCCGGGAGGGGAGGGCGTTTGCTTGGCTCTTCTCGATACTGGAGAAGCAGGG
GCTGGGCCCTTAAGAACAGCCCGCCCGAGTTTTCGAAGCTGCGGTAGAGAAACCCCATCCCCCCCAAATCCTGTAACTCACACCCCCTCTCGCCCCTGCCCGGGCTCTGACCCCGGAGAGAGGGGCTGGGCTGATCAGGGCGGGGCGAAGTCTTCTCCTAGTTGAGCGAGAAGGAGGCCCCTTTGGGCTTAGCCAAG

Craig Venter Francis Collins

ACTGAAAGTCTCCACCAACCCGGCGGGGTTGGGGGCTTCTCTCCCCAAGTCACTCTCAGGGCAGCTCCTCCCCTCCTCACCCCACTACGGGCCTAGAAGGGATGGGGAGAGGAGCCCCCAGGCCTGCAGCAGGGTAGGGGTGGTAAACTCGCTGTTACAGGGCGCGGGAGAGAGCACGGTTTACTGGGTCTGGTAAG
GAGGTGCCCAGGAATTGGAAAATCCCTGCCCTGGCAACTGCAATTGCTTGGGTCCTGATAGTCCCAGGCCCAGAGCGCTTTTGATACTTATGGCCCTTGTACCTCCCTGCTTTCCTCTGCCCAGACCCCGTGGGGTCCCACCCACCTTCCTGTTCGTGGTGGGTGCTGGTACGCGGCAGGGCTAGTCTAGAGCTCCG
ACCTGGGAGCCTGGAGGCCCAGCGAAACCAGGCCCGGTTTGAGGTTACGGTTGAGGCACACGGCGTCGGGGCTCAACTGAACTCAAAGTGTGGAAAGGCCCGGGTCTTCCAGCAGCCTGCCCTGGCCGAACCACACAGGCTTAAGGAGGGTCCCCAGCACCTTATCCATCTGTTTTGGAAACGCCGGTCGCCCCCTG
GTGCTTCCGGGGCTGGTAAGCGCGTAGCTGAGGAAAGGGCACAAAGGTGGCGAGCTTTGCGGGAGTAGTTGTGCAGAACCTGCCGGACCCCAGGGCTTGGCCGGTAGGCTCGCCTTCGGCGGCTGGGCTCTCCCCTTGGAGCTCAGACTCCCCAGCCGCAGGCTGTCTCTCGGGCGGGCCCCAGCCAGGGCGCGCAG
CCCTGAGCGTTTGTCGCTGCGGCCCGGCTGGCAGGCCCCGAGGGGCGCGGGGTCGCGGGCCGGCCGGCAGGGCTTTGTGCCGCTCGTTCCCGGGTGTGCGCGAGGCGCGGAGCATCCAAATTGACACCATATGTTTTCCTATTAGTTGCTTCGCGGTCGAGTTCTAGGCGCATAATCATCGCCAGTGGGCGAGAGCG
CCAGCAGTCCCTAGGGAAGGGACACAATGATTGAGGCTTAACCTCTGAAGGGGAATTTGGAGCTGCGCTTTCTCTCTGCCATTTCGATGCTGGGAGTGGCGCTCTGGCCCTGGCGTCTCCTGGGCAAGCACCAGCCGGCGGTATCTGCGGAGGTGGCTGGCACGTTGTTATTTTTTGAAATGAGTGAGGAGGGAGGT
CTAGATTTAGGCGGCCTTACGCGCCCGCCTTGGCATTAGCAGACTGGGAATTGCCGTGGCTATGCCCGAAGTTTGGAAAGTCTCTCTCGGTCTCTTTCTGGGACAGCCTTTCTTTTTCCGGGAAGCTTCCTGTGCCTAGAGGTGGGGCTCTGTAGCTGGAGGGGTAGATGGAACTTGCGAAGCAAAGGAAGGCAATA
AAAGGAAGTTAGGAGAAACCGGAAACGTGGGCCAGGCCTTGCTCTGTTGGAGAAGCGGTGTCCCCGCAAAGTCCCTGCTTGCGCTGGTCCCGGCCGGAGCCCAGATCCCCCAAACGCCTGTCACTTCTCATCGAGTTGAGGCTCCGGCCCCCACCCGCGCCTTGGTGAGGGCCCCCCCTCAGCCCCAAGCCTTCGGC
TACCCTGAAAACGCGGCTCCCCTCGAAGGGGAAACAAGTGCAGTTCAATCTCGTCTGAGTGATCTACAAATAAGGACGGAAAGGGTCGTTTTATCACGGTCCCGTTTGTCGTGACGATGCAATTTCCCGGAGCGGAGCACTGTCACAAAGTGACAAGGCTGCCACAAGCGCCCCGACTGATCTTTTCAATTAGCCTT
CCATGCATGATCCGGAGCGACTTCCGCCTATTTCCAGAAATTAAGCTCAAACTTGACGTGCAGCTAGTTTTATTTTAAAGACAAATGTCAGAGAGGCTCATCATATTTTCCCCCCTCTTCTATATTTGGAGCTTATTTATTGCTAAGAAGCTCAGGCTCCTGGCGTCAATTTATCAGTAGGCTCCAAGGAGAAGAGA
GGAGAGGAGAGGAGAGCTGAACAGGGAGCCACGTCTTTTCCTGGGAGGGCTGCTATCTAAGTCGGGGCTGCAGGTTGGAGATTTTTAAGGAAGTGGAAATTGGCAATTGGCTTTGTGTGTCTGTGGTTTTTGGGGAGGGGGACTACAAAGAGGGGCTAACTCCCTCTCCCTATTCTCTAAGGTTGGACCACAGGGAT
GAGGTTGTGAGATACAAAGATAAAGGAGGGATGGGGAACACTATGATGTGGTATTTTTCTTTTCTGTTTTTTCTTTTTGATAATATCTATCCTTGGCTAAGGGGAGGGCGGAGTTCAGCGGCGGAAATAAAGCGAGCAGTGGCTGGTGCGAACCGACTCCCGGCTCTAAGCCTTACTTGCGGTGGCCGGACTTGTCT
GTGGCTGAAGCCGAGCCCGGGCTCTGACTCTCACGTCTGCACTGGAGGTGCGGAAACCTGGACTGGGGTTCACCAGCCACATACTGGCTGCTCTGGTTGTTCTCTCCTCTTCCTTCTTCTATTCTAACCAAACAAAACCCAACTCGATGCTTGTGCCAGGCCTTGGCCAGTTTGGACGGTGATGGAAACATTTCTGG
ATTTTAGCGTCTAAGGGAGCACTCAAGGGCTGTAAGGTTTGCTATCACTGTCCCAACACTGCAGAGACCTTGAAGGTTCAGTGTGGGATCTGTAGAACCCATGGTTTGCGGTGACACTCAGAGGGGATCTTTGGGAGATTTATAGAGCCGGTTCTTAGCGCTTTGTGGGTTCAGAGGCTGGCTGCAGTGTTTATGAA
GAGGGGCAGTGGGCTGGGGACACTGCTGGGGTTATGGCTGTAGTGAGGTCCATGTGTACTTGTTCCTTGGCATGTGTCTGACTCTGTGTTGCTGCTGCAGTACAGTGGGCAGGGGCACGGTTGCTTGGACTGGGCTGCCCGATGTCTGGCATGGCTGGTGGTCCTGTTGTCCTTTATTTGATCGATAGCAGGGAACT
GACCGCCGAGGTTGGCACAGGTTGGCAGGGGGATGAGGATGCATTGTGGTTGTCTCCTCCTCCTCTCCTTCTTCCTCTTCCCCTTCCTCCTCTCCTTTCTGTTCTTGTTCTCCCTCATCTTCCTCTTCCTTCTTCTCCCTCTTCTTCCTCTTCACTCTGCTCTCTTCTCTTCTTTTCCCCTTTCCTCTCCTCTCCCT
TTCCTCAGGTCACAGCGGAGTGAATCAGCTCGGTGGTGTCTTTGTCAACGGGCGGCCACTGCCGGACTCCACCCGGCAGAAGATTGTAGAGCTAGCTCACAGCGGGGCCCGGCCGTGCGACATTTCCCGAATTCTGCAGGTGATCCTCCCGGCGCCGCCCCACTCGCCGCCCCCGCGGCCCTCCACTCTCAACGCCC
TCTCTTCATTTCTTACTGTAAACGATGCTAATTATGGACCCCCCCACCCTCACCCACCCCAGTCCCCAGTCCCCCCACCCACTCCCCTGCCTTCCCACTTTCCCCTCTCCTTCCACCATCCTTCCCTATCTCTTTCAACCTGGGTCAGTTACATAAGATAACTCATCTGCTTCAGAAAAATATTGTGTGCGGATTTT
TTTAAAAAAATCTTTCTCTTTTTATTTGGTAAAGACATTCATTGTGGGAACAGTTTATGAACCGTAATAAGCTGAGTTATATAAACCGGCATAATTTCATTCTGCTCTCCCCAGCCCATGCTTACCTCAGCTTTTGAGGTATTTGTTTATTCTTCATGTTTATGAATAATATATATTGATTTTAAAAGGCAAATGCT
ATTTACTCCTCCCTAACTCACATTTACTCAATTGAGTATTTTTTAAAGAAGAAGAAGTAAAAAAATCAGTTTATTTTTTACCTTTGTTCTTTAAAACATAACGCCACTTTAAGCAAGGTCAGCACAAAAATAAATTTATCTACTTCGTTTTGATGCATCTTCAGGCAGTGTTTAAGAAAAGTTTTTTTTTTAAAAAA
AGCTTTTAAATTCGTTTTTTAGTTCAAATTGTTTGAAAGTATCATCATATTTGTAGTTTTTAGGGCTACAAATGTAATTTTAAGAAAAAAAGCTCTCTACAGTAAGTTCTCATACCATTGAAGGTATATTTTTGTGTTATAGACCCATGCAGATGCAAAAGTCCAAGTGCTGGACAATCAAAACGTAAGCTTGTCAT
TGTTTAATGCATACTTAAACAATTTTATTTTTGTCTTGAAATTATTAATAATGTGGTTTTCTGTCCACTTCCCCTATGCAGGTGTCCAACGGATGTGTGAGTAAAATTCTGGGCAGGTATTACGAGACTGGCTCCATCAGACCCAGGGCAATCGGTGGTAGTAAACCGAGAGTAGCGACTCCAGAAGTTGTAAGCAA
AATAGCCCAGTATAAGCGGGAGTGCCCGTCCATCTTTGCTTGGGAAATCCGAGACAGATTACTGTCCGAGGGGGTCTGTACCAACGATAACATACCAAGCGTAAGTTCATTGAGAACATCTGCCCTCCCTGCCCTAAGCCCAATGCTCTCTCCTCTTTACCTCCTCCCACCCTCTCTCTCCACTGTCTCTTAGTCTG
TGTCCTCTCCCTGCTCCACATTTGTCTCCTTTGTACCTGGGGGAACAGAGAGGAATGCCCTGACTTTTCTTTGACTGTCTGGAAAATGGGAGTCAAGTGTGGGGAGTCATTCACTTCATTTGCATGCTGCAAAACAGAGGGCGGAGGCACCAGGGAAAGGCACTTGAATGAAGAAGGAAAATGAGAACCAGATTGTA
ACTTCGTCCTAATCCACCTGCCAGAACTTTCCTTCAGGTGTCACACATCCATTTCCATCCTAATATTAAACAATATAATGAAAGAAAGCTTTACAACAAGTCTAAATAGTTTTTATTTTCGGGCAGTCTTTTAACAAAGCAAAGCAACCGTGTGAGTTAGGTCACCAGAGACACCAAGCAATGGTGAAGGACCCCCT
CCGCCCAATTCTCTATCCAACTAAATTTCCATGCCCAAAGTGATAGCTATCATTTTTTCCACGGTGTATCTGCAAATCCACCCACTGTCCCGGGGTGGCTGGGAGCTTTTTAACGGGTTGAGAGTTGCTTTTTAAGGTTGTGGGTGAGCTGAGATGGGTGACTGTGTCTTCAGGAGACACTACCATTTGGTTTGATT
TTGGTTTGATTTGCAGGTGTCATCAATAAACAGAGTTCTTCGCAACCTGGCTAGCGAAAAGCAACAGATGGGCGCAGACGGCATGTATGATAAAAGTCCCCCCACCCACTCCCCTGCCTTCCCACTTTCCCCTCTCCTTCCACCATCCTTCCCTATCTCTTTCAACCTGGGTCAGTTACATAAGATAACTCATCTGC
TTCAGAAAAATATTGTGTGCGGATTTTTTTAAAAAAATCTTTCTCTTTTTATTTGGTAAAGACATTCATTGTGGGAACAGTTTATGAACCGTAATAAGCTGAGTTATATAAACCGGCATAATTTCATTCTGCTCTCCCCAGCCCATGCTTACCTCAGCTTTTGAGGTATTTGTTTATTCTTCATGTTTATGAATAAT
ATATATTGATTTTAAAAGGCAAATGCTATTTACTCCTCCCTAACTCACATTTACTCAATTGAGTATTTTTTAAAGAAGAAGAAGTAAAAAAATCAGTTTATTTTTTACCTTTGTTCTTTAAAACATAACGCCACTTTAAGCAAGGTCAGCACAAAAATAAATTTATCTACTTCGTTTTGATGCATCTTCAGGCAGTG
TTTAAGAAAAGTTTTTTTTTTAAAAAAAGCTTTTAAATTCGTTTTTTAGTTCAAATTGTTTGAAAGTATCATCATATTTGTAGTTTTTAGGGCTACAAATGTAATTTTAAGAAAAAAAGCTCTCTACAGTAAGTTCTCATACCATTGAAGGTATATTTTTGTGTTATAGACCCATGCAGATGCAAAAGTCCAAGTGC
TGGACAATCAAAACGTAAGCTTGTCATTGTTTAATGCATACTTAAACAATTTTATTTTTGTCTTGAAATTATTAATAATGTGGTTTTCTGTCCACTTCCCCTATGCAGGTGTCCAACGGATGTGTGAGTAAAATTCTGGGCAGGTATTACGAGACTGGCTCCATCAGACCCAGGGCAATCGGTGGTAGTAAACCGAG
AGTAGCGACTCCAGAAGTTGTAAGCAAAATAGCCCAGTATAAGCGGGAGTGCCCGTCCATCTTTGCTTGGGAAATCCGAGACAGATTACTGTCCGAGGGGGTCTGTACCAACGATAACATACCAAGCGTAAGTTCATTGAGAACATCTGCCCTCCCTGCCCTAAGCCCAATGCTCTCTCCTCTTTACCTCCTCCCAC
CCTCTCTCTCCACTGTCTCTTAGTCTGTGTCCTCTCCCTGCTCCACATTTGTCTCCTTTGTACCTGGGGGAACAGAGAGGAATGCCCTGACTTTTCTTTGACTGTCTGGAAAATGGGAGTCAAGTGTGGGGAGTCATTCACTTCATTTGCATGCTGCAAAACAGAGGGCGGAGGCACCAGGGAAAGGCACTTGAATG
AAGAAGGAAAATGAGAACCAGATTGTAACTTCGTCCTAATCCACCTGCCAGAACTTTCCTTCAGGTGTCACACATCCATTTCCATCCTAATATTAAACAATATAATGAAAGAAAGCTTTACAACAAGTCTAAATAGTTTTTATTTTCGGGCAGTCTTTTAACAAAGCAAAGCAACCGTGTGAGTTAGGTCACCAGAG
ACACCAAGCAATGGTGAAGGACCCCCTCCGCCCAATTCTCTATCCAACTAAATTTCCATGCCCAAAGTGATAGCTATCATTTTTTCCACGGTGTATCTGCAAATCCACCCACTGTCCCGGGGTGGCTGGGAGCTTTTTAACGGGTTGAGAGTTGCTTTTTAAGGTTGTGGGTGAGCTGAGATGGGTGACTGTGTCTT
CAGGAGACACTACCATTTGGTTTGATTTTGGTTTGATTTGCAGGTGTCATCAATAAACAGAGTTCTTCGCAACCTGGCTAGCGAAAAGCAACAGATGGGCGCAGACGGCATGTATGATAATAAAATTCTGGGCAGGTATTACGAGACTGGCTCCATCAGACCCAGGGCAATCGGTGGTAGTAAACCGAGAGTAGCGA
CTCCAGAAGTTGTAAGCAAAATAGCCCAGTATAAGCGGGAGTGCCCGTCCATCTTTGCTTGGGAAATCCGAGACAGATTACTGTCCGAGGGGGTCTGTACCAACGATAACATACCAAGCGTAAGTTCATTGAGAACATCTGCCCTCCCTGCCCTAAGCCCAATGCTCTCTCCTCTTTACCTCCTCCCACCCTCTCTC
TCCACTGTCTCTTAGTCTGTGTCCTCTCCCTGCTCCACATTTGTCTCCTTTGTACCTGGGGGAACAGAGAGGAATGCCCTGACTTTTCTTTGACTGTCTGGAAAATGGGAGTCAAGTGTGGGGAGTCATTCACTTCATTTGCATGCTGCAAAACAGAGGGCGGAGGCACCAGGGAAAGGCACTTGAATGAAGAAGGA
AAATGAGAACCAGATTGTAACTTCGTCCTAATCCACCTGCCAGAACTTTCCTTCAGGTGTCACACATCCATTTCCATCCTAATATTAAACAATATAATGAAAGAAAGCTTTACAACAAGTCTAAATAGTTTTTATTTTCGGGCAGTCTTTTAACAAAGCAAAGCAACCGTGTGAGTTAGGTCACCAGAGACACCAAG
CAATGGTGAAGGACCCCCTCCGCCCAATTCTCTATCCAACTAAATTTCCATGCCCAAAGTGATAGCTATCATTTTTTCCACGGTGTATCTGCAAATCCACCCACTGTCCCGGGGTGGCTGGGAGCTTTTTAACGGGTTGAGAGTTGCTTTTTAAGGTTGTGGGTGAGCTGAGATGGGTGACTGTGTCTTCAGGAGAC
ACTACCATTTGGTTTGATTTTGGTTTGATTTGCAGGTGTCATCAATAAACAGAGTTCTTCGCAACCTGGCTAGCGAAAAGCAACAGATGGGCGCAGACGGCATGTATGATAAACTCCAGAAGTTGTAAGCAAAATAGCCCAGTATAAGCGGGAGTGCCCGTCCATCTTTGCTTGGGAAATCCGAGACAGATTACTGT
CCGAGGGGGTCTGTACCAACGATAACATACCAAGCGTAAGTTCATTGAGAACATCTGCCCTCCCTGCCCTAAGCCCAATGCTCTCTCCTCTTTACCTCCTCCCACCCTCTCTCTCCACTGTCTCTTAGTCTGTGTCCTCTCCCTGCTCCACATTTGTCTCCTTTGTACCTGGGGGAACAGAGAGGAATGCCCTGACT
TTTCTTTGACTGTCTGGAAAATGGGAGTCAAGTGTGGGGAGTCATTCACTTCATTTGCATGCTGCAAAACAGAGGGCGGAGGCACCAGGGAAAGGCACTTGAATGAAGAAGGAAAATGAGAACCAGATTGTAACTTCGTCCTAATCCACCTGCCAGAACTTTCCTTCAGGTGTCACACATCCATTTCCATCCTAATA
ACTACCATTTGGTTTGATTTTGGTTTGATTTGCAGGTGTCATCAATAAACAGAGTTCTTCGCAACCTGGCTAGCGAAAAGCAACAGATGGGCGCAGAC
GGCATGTATGATAAAAGTCCCCCCACCCACTCCCCTGCCTTCCCACTTTCCCCTCTCCTTCCACCATCCTTCCCTATCTCTTTCAACCTGGGTCAGTT
ACATAAGATAACTCATCTGCTTCAGAAAAATATTGTGTGCGGATTTTTTTAAAAAAATCTTTCTCTTTTTATTTGGTAAAGACATTCATTGTGGGAAC
AGTTTATGAACCGTAATAAGCTGAGTTATATAAACCGGCATAATTTCATTCTGCTCTCCCCAGCCCATGCTTACCTCAGCTTTTGAGGTATTTGTTTA
TTCTTCATGTTTATGAATAATATATATTGATTTTAAAAGGCAAATGCTATTTACTCCTCCCTAACTCACATTTACTCAATTGAGTATTTTTTAAAGAA
GAAGAAGTAAAAAAATCAGTTTATTTTTTACCTTTGTTCTTTAAAACATAACGCCACTTTAAGCAAGGTCAGCACAAAAATAAATTTATCTACTTCGT
TTTGATGCATCTTCAGGCAGTGTTTAAGAAAAGTTTTTTTTTTAAAAAAAGCTTTTAAATTCGTTTTTTAGTTCAAATTGTTTGAAAGTATCATCATA
TTTGTAGTTTTTAGGGCTACAAATGTAATTTTAAGAAAAAAAGCTCTCTACAGTAAGTTCTCATACCATTGAAGGTATATTTTTGTGTTATAGACCCA
TGCAGATGCAAAAGTCCAAGTGCTGGACAATCAAAACGTAAGCTTGTCATTGTTTAATGCATACTTAAACAATTTTATTTTTGTCTTGAAATTATTAA
TAATGTGGTTTTCTGTCCACTTCCCCTATGCAGGTGTCCAACGGATGTGTGAGTAAAATTCTGGGCAGGTATTACGAGACTGGCTCCATCAGACCCAG
GGCAATCGGTGGTAGTAAACCGAGAGTAGCGACTCCAGAAGTTGTAAGCAAAATAGCCCAGTATAAGCGGGAGTGCCCGTCCATCTTTGCTTGGGAAA
TCCGAGACAGATTACTGTCCGAGGGGGTCTGTACCAACGATAACATACCAAGCGTAAGTTCATTGAGAACATCTGCCCTCCCTGCCCTAAGCCCAATG
CTCTCTCCTCTTTACCTCCTCCCACCCTCTCTCTCCACTGTCTCTTAGTCTGTGTCCTCTCCCTGCTCCACATTTGTCTCCTTTGTACCTGGGGGAAC
AGAGAGGAATGCCCTGACTTTTCTTTGACTGTCTGGAAAATGGGAGTCAAGTGTGGGGAGTCATTCACTTCATTTGCATGCTGCAAAACAGAGGGCGG
AGGCACCAGGGAAAGGCACTTGAATGAAGAAGGAAAATGAGAACCAGATTGTAACTTCGTCCTAATCCACCTGCCAGAACTTTCCTTCAGGTGTCACA
CATCCATTTCCATCCTAATATTAAACAATATAATGAAAGAAAGCTTTACAACAAGTCTAAATAGTTTTTATTTTCGGGCAGTCTTTTAACAAAGCAAA
GCAACCGTGTGAGTTAGGTCACCAGAGACACCAAGCAATGGTGAAGGACCCCCTCCGCCCAATTCTCTATCCAACTAAATTTCCATGCCCAAAGTGAT
AGCTATCATTTTTTCCACGGTGTATCTGCAAATCCACCCACTGTCCCGGGGTGGCTGGGAGCTTTTTAACGGGTTGAGAGTTGCTTTTTAAGGTTGTG
GGTGAGCTGAGATGGGTGACTGTGTCTTCAGGAGACACTACCATTTGGTTTGATTTTGGTTTGATTTGCAGGTGTCATCAATAAACAGAGTTCTTCGC
AACCTGGCTAGCGAAAAGCAACAGATGGGCGCAGACGGCATGTATGATAATAAAATTCTGGGCAGGTATTACGAGACTGGCTCCATCAGACCCAGGGC
AATCGGTGGTAGTAAACCGAGAGTAGCGACTCCAGAAGTTGTAAGCAAAATAGCCCAGTATAAGCGGGAGTGCCCGTCCATCTTTGCTTGGGAAATCC
GAGACAGATTACTGTCCGAGGGGGTCTGTACCAACGATAACATACCAAGCGTAAGTTCATTGAGAACATCTGCCCTCCCTGCCCTAAGCCCAATGCTC
TCTCCTCTTTACCTCCTCCCACCCTCTCTCTCCACTGTCTCTTAGTCTGTGTCCTCTCCCTGCTCCACATTTGTCTCCTTTGTACCTGGGGGAACAGA
GAGGAATGCCCTGACTTTTCTTTGACTGTCTGGAAAATGGGAGTCAAGTGTGGGGAGTCATTCACTTCATTTGCATGCTGCAAAACAGAGGGCGGAGG
CACCAGGGAAAGGCACTTGAATGAAGAAGGAAAATGAGAACCAGATTGTAACTTCGTCCTAATCCACCTGCCAGAACTTTCCTTCAGGTGTCACACAT
CCATTTCCATCCTAATATTAAACAATATAATGAAAGAAAGCTTTACAACAAGTCTAAATAGTTTTTATTTTCGGGCAGTCTTTTAACAAAGCAAAGCA
ACCGTGTGAGTTAGGTCACCAGAGACACCAAGCAATGGTGAAGGACCCCCTCCGCCCAATTCTCTATCCAACTAAATTTCCATGCCCAAAGTGATAGC
TATCATTTTTTCCACGGTGTATCTGCAAATCCACCCACTGTCCCGGGGTGGCTGGGAGCTTTTTAACGGGTTGAGAGTTGCTTTTTAAGGTTGTGGGT
GAGCTGAGATGGGTGACTGTGTCTTCAGGAGACACTACCATTTGGTTTGATTTTGGTTTGATTTGCAGGTGTCATCAATAAACAGAGTTCTTCGCAAC
CTGGCTAGCGAAAAGCAACAGATGGGCGCAGACGGCATGTATGATAAACTCCAGAAGTTGTAAGCAAAATAGCCCAGTATAAGCGGGAGTGCCCGTCC
ATCTTTGCTTGGGAAATCCGAGACAGATTACTGTCCGAGGGGGTCTGTACCAACGATAACATACCAAGCGTAAGTTCATTGAGAACATCTGCCCTCCC
TGCCCTAAGCCCAATGCTCTCTCCTCTTTACCTCCTCCCACCCTCTCTCTCCACTGTCTCTTAGTCTGTGTCCTCTCCCTGCTCCACATTTGTCTCCT
TTGTACCTGGGGGAACAGAGAGGAATGCCCTGACTTTTCTTTGACTGTCTGGAAAATGGGAGTCAAGTGTGGGGAGTCATTCACTTCATTTGCATGCT
GCAAAACAGAGGGCGGAGGCACCAGGGAAAGGCACTTGAATGAAGAAGGAAAATGAGAACCAGATTGTAACTTCGTCCTAATCCACCTGCCAGAACTT
TCCTTCAGGTGTCACACATCCATTTCCATCCTAATATTAAACAATATAATGAAAGAAAGCTTTACAACAAGTCTAAATAGTTTTTATTTTCGGGCAGT
CTTTTAACAAAGCAAAGCAACCGTGTGAGTTAGGTCACCAGAGACACCAAGCAATGGTGAAGGACCCCCTCCGCCCAATTCTCTATCCAACTAAATTT
CCATGCCCAAAGTGATAGCTATCATTTTTTCCACGGTGTATCTGCAAATCCACCCACTGTCCCGGGGTGGCTGGGAGCTTTTTAACGGGTTGAGAGTT
ACTACCATTTGGTTTGATTTTGGTTTGATTTGCAGGTGTCATCAATAAACAGAGTTCTTCGCAACCTGGCTAGCGAAAAGCAACAGATGGGCGCAGAC
GGCATGTATGATAAAAGTCCCCCCACCCACTCCCCTGCCTTCCCACTTTCCCCTCTCCTTCCACCATCCTTCCCTATCTCTTTCAACCTGGGTCAGTT
ACATAAGATAACTCATCTGCTTCAGAAAAATATTGTGTGCGGATTTTTTTAAAAAAATCTTTCTCTTTTTATTTGGTAAAGACATTCATTGTGGGAAC
AGTTTATGAACCGTAATAAGCTGAGTTATATAAACCGGCATAATTTCATTCTGCTCTCCCCAGCCCATGCTTACCTCAGCTTTTGAGGTATTTGTTTA
TTCTTCATGTTTATGAATAATATATATTGATTTTAAAAGGCAAATGCTATTTACTCCTCCCTAACTCACATTTACTCAATTGAGTATTTTTTAAAGAA
GAAGAAGTAAAAAAATCAGTTTATTTTTTACCTTTGTTCTTTAAAACATAACGCCACTTTAAGCAAGGTCAGCACAAAAATAAATTTATCTACTTCGT
TTTGATGCATCTTCAGGCAGTGTTTAAGAAAAGTTTTTTTTTTAAAAAAAGCTTTTAAATTCGTTTTTTAGTTCAAATTGTTTGAAAGTATCATCATA
TTTGTAGTTTTTAGGGCTACAAATGTAATTTTAAGAAAAAAAGCTCTCTACAGTAAGTTCTCATACCATTGAAGGTATATTTTTGTGTTATAGACCCA
TGCAGATGCAAAAGTCCAAGTGCTGGACAATCAAAACGTAAGCTTGTCATTGTTTAATGCATACTTAAACAATTTTATTTTTGTCTTGAAATTATTAA
TAATGTGGTTTTCTGTCCACTTCCCCTATGCAGGTGTCCAACGGATGTGTGAGTAAAATTCTGGGCAGGTATTACGAGACTGGCTCCATCAGACCCAG
GGCAATCGGTGGTAGTAAACCGAGAGTAGCGACTCCAGAAGTTGTAAGCAAAATAGCCCAGTATAAGCGGGAGTGCCCGTCCATCTTTGCTTGGGAAA
TCCGAGACAGATTACTGTCCGAGGGGGTCTGTACCAACGATAACATACCAAGCGTAAGTTCATTGAGAACATCTGCCCTCCCTGCCCTAAGCCCAATG
CTCTCTCCTCTTTACCTCCTCCCACCCTCTCTCTCCACTGTCTCTTAGTCTGTGTCCTCTCCCTGCTCCACATTTGTCTCCTTTGTACCTGGGGGAAC
AGAGAGGAATGCCCTGACTTTTCTTTGACTGTCTGGAAAATGGGAGTCAAGTGTGGGGAGTCATTCACTTCATTTGCATGCTGCAAAACAGAGGGCGG
AGGCACCAGGGAAAGGCACTTGAATGAAGAAGGAAAATGAGAACCAGATTGTAACTTCGTCCTAATCCACCTGCCAGAACTTTCCTTCAGGTGTCACA
CATCCATTTCCATCCTAATATTAAACAATATAATGAAAGAAAGCTTTACAACAAGTCTAAATAGTTTTTATTTTCGGGCAGTCTTTTAACAAAGCAAA
GCAACCGTGTGAGTTAGGTCACCAGAGACACCAAGCAATGGTGAAGGACCCCCTCCGCCCAATTCTCTATCCAACTAAATTTCCATGCCCAAAGTGAT
AGCTATCATTTTTTCCACGGTGTATCTGCAAATCCACCCACTGTCCCGGGGTGGCTGGGAGCTTTTTAACGGGTTGAGAGTTGCTTTTTAAGGTTGTG
GGTGAGCTGAGATGGGTGACTGTGTCTTCAGGAGACACTACCATTTGGTTTGATTTTGGTTTGATTTGCAGGTGTCATCAATAAACAGAGTTCTTCGC
AACCTGGCTAGCGAAAAGCAACAGATGGGCGCAGACGGCATGTATGATAATAAAATTCTGGGCAGGTATTACGAGACTGGCTCCATCAGACCCAGGGC
AATCGGTGGTAGTAAACCGAGAGTAGCGACTCCAGAAGTTGTAAGCAAAATAGCCCAGTATAAGCGGGAGTGCCCGTCCATCTTTGCTTGGGAAATCC
GAGACAGATTACTGTCCGAGGGGGTCTGTACCAACGATAACATACCAAGCGTAAGTTCATTGAGAACATCTGCCCTCCCTGCCCTAAGCCCAATGCTC
TCTCCTCTTTACCTCCTCCCACCCTCTCTCTCCACTGTCTCTTAGTCTGTGTCCTCTCCCTGCTCCACATTTGTCTCCTTTGTACCTGGGGGAACAGA
GAGGAATGCCCTGACTTTTCTTTGACTGTCTGGAAAATGGGAGTCAAGTGTGGGGAGTCATTCACTTCATTTGCATGCTGCAAAACAGAGGGCGGAGG
CACCAGGGAAAGGCACTTGAATGAAGAAGGAAAATGAGAACCAGATTGTAACTTCGTCCTAATCCACCTGCCAGAACTTTCCTTCAGGTGTCACACAT
CCATTTCCATCCTAATATTAAACAATATAATGAAAGAAAGCTTTACAACAAGTCTAAATAGTTTTTATTTTCGGGCAGTCTTTTAACAAAGCAAAGCA
ACCGTGTGAGTTAGGTCACCAGAGACACCAAGCAATGGTGAAGGACCCCCTCCGCCCAATTCTCTATCCAACTAAATTTCCATGCCCAAAGTGATAGC
TATCATTTTTTCCACGGTGTATCTGCAAATCCACCCACTGTCCCGGGGTGGCTGGGAGCTTTTTAACGGGTTGAGAGTTGCTTTTTAAGGTTGTGGGT
GAGCTGAGATGGGTGACTGTGTCTTCAGGAGACACTACCATTTGGTTTGATTTTGGTTTGATTTGCAGGTGTCATCAATAAACAGAGTTCTTCGCAAC
CTGGCTAGCGAAAAGCAACAGATGGGCGCAGACGGCATGTATGATAAACTCCAGAAGTTGTAAGCAAAATAGCCCAGTATAAGCGGGAGTGCCCGTCC
ATCTTTGCTTGGGAAATCCGAGACAGATTACTGTCCGAGGGGGTCTGTACCAACGATAACATACCAAGCGTAAGTTCATTGAGAACATCTGCCCTCCC
TGCCCTAAGCCCAATGCTCTCTCCTCTTTACCTCCTCCCACCCTCTCTCTCCACTGTCTCTTAGTCTGTGTCCTCTCCCTGCTCCACATTTGTCTCCT
TTGTACCTGGGGGAACAGAGAGGAATGCCCTGACTTTTCTTTGACTGTCTGGAAAATGGGAGTCAAGTGTGGGGAGTCATTCACTTCATTTGCATGCT
GCAAAACAGAGGGCGGAGGCACCAGGGAAAGGCACTTGAATGAAGAAGGAAAATGAGAACCAGATTGTAACTTCGTCCTAATCCACCTGCCAGAACTT
TCCTTCAGGTGTCACACATCCATTTCCATCCTAATATTAAACAATATAATGAAAGAAAGCTTTACAACAAGTCTAAATAGTTTTTATTTTCGGGCAGT
CTTTTAACAAAGCAAAGCAACCGTGTGAGTTAGGTCACCAGAGACACCAAGCAATGGTGAAGGACCCCCTCCGCCCAATTCTCTATCCAACTAAATTT
CCATGCCCAAAGTGATAGCTATCATTTTTTCCACGGTGTATCTGCAAATCCACCCACTGTCCCGGGGTGGCTGGGAGCTTTTTAACGGGTTGAGAGTT
ACTACCATTTGGTTTGATTTTGGTTTGATTTGCAGGTGTCATCAATAAACAGAGTTCTTCGCAACCTGGCTAGCGAAAAGCAACAGATGGGCGCAGAC
GGCATGTATGATAAAAGTCCCCCCACCCACTCCCCTGCCTTCCCACTTTCCCCTCTCCTTCCACCATCCTTCCCTATCTCTTTCAACCTGGGTCAGTT
ACATAAGATAACTCATCTGCTTCAGAAAAATATTGTGTGCGGATTTTTTTAAAAAAATCTTTCTCTTTTTATTTGGTAAAGACATTCATTGTGGGAAC
AGTTTATGAACCGTAATAAGCTGAGTTATATAAACCGGCATAATTTCATTCTGCTCTCCCCAGCCCATGCTTACCTCAGCTTTTGAGGTATTTGTTTA
TTCTTCATGTTTATGAATAATATATATTGATTTTAAAAGGCAAATGCTATTTACTCCTCCCTAACTCACATTTACTCAATTGAGTATTTTTTAAAGAA
GAAGAAGTAAAAAAATCAGTTTATTTTTTACCTTTGTTCTTTAAAACATAACGCCACTTTAAGCAAGGTCAGCACAAAAATAAATTTATCTACTTCGT
TTTGATGCATCTTCAGGCAGTGTTTAAGAAAAGTTTTTTTTTTAAAAAAAGCTTTTAAATTCGTTTTTTAGTTCAAATTGTTTGAAAGTATCATCATA
TTTGTAGTTTTTAGGGCTACAAATGTAATTTTAAGAAAAAAAGCTCTCTACAGTAAGTTCTCATACCATTGAAGGTATATTTTTGTGTTATAGACCCA
TGCAGATGCAAAAGTCCAAGTGCTGGACAATCAAAACGTAAGCTTGTCATTGTTTAATGCATACTTAAACAATTTTATTTTTGTCTTGAAATTATTAA
TAATGTGGTTTTCTGTCCACTTCCCCTATGCAGGTGTCCAACGGATGTGTGAGTAAAATTCTGGGCAGGTATTACGAGACTGGCTCCATCAGACCCAG
GGCAATCGGTGGTAGTAAACCGAGAGTAGCGACTCCAGAAGTTGTAAGCAAAATAGCCCAGTATAAGCGGGAGTGCCCGTCCATCTTTGCTTGGGAAA
TCCGAGACAGATTACTGTCCGAGGGGGTCTGTACCAACGATAACATACCAAGCGTAAGTTCATTGAGAACATCTGCCCTCCCTGCCCTAAGCCCAATG
CTCTCTCCTCTTTACCTCCTCCCACCCTCTCTCTCCACTGTCTCTTAGTCTGTGTCCTCTCCCTGCTCCACATTTGTCTCCTTTGTACCTGGGGGAAC
AGAGAGGAATGCCCTGACTTTTCTTTGACTGTCTGGAAAATGGGAGTCAAGTGTGGGGAGTCATTCACTTCATTTGCATGCTGCAAAACAGAGGGCGG
AGGCACCAGGGAAAGGCACTTGAATGAAGAAGGAAAATGAGAACCAGATTGTAACTTCGTCCTAATCCACCTGCCAGAACTTTCCTTCAGGTGTCACA
CATCCATTTCCATCCTAATATTAAACAATATAATGAAAGAAAGCTTTACAACAAGTCTAAATAGTTTTTATTTTCGGGCAGTCTTTTAACAAAGCAAA
GCAACCGTGTGAGTTAGGTCACCAGAGACACCAAGCAATGGTGAAGGACCCCCTCCGCCCAATTCTCTATCCAACTAAATTTCCATGCCCAAAGTGAT
AGCTATCATTTTTTCCACGGTGTATCTGCAAATCCACCCACTGTCCCGGGGTGGCTGGGAGCTTTTTAACGGGTTGAGAGTTGCTTTTTAAGGTTGTG
GGTGAGCTGAGATGGGTGACTGTGTCTTCAGGAGACACTACCATTTGGTTTGATTTTGGTTTGATTTGCAGGTGTCATCAATAAACAGAGTTCTTCGC
AACCTGGCTAGCGAAAAGCAACAGATGGGCGCAGACGGCATGTATGATAATAAAATTCTGGGCAGGTATTACGAGACTGGCTCCATCAGACCCAGGGC
AATCGGTGGTAGTAAACCGAGAGTAGCGACTCCAGAAGTTGTAAGCAAAATAGCCCAGTATAAGCGGGAGTGCCCGTCCATCTTTGCTTGGGAAATCC
GAGACAGATTACTGTCCGAGGGGGTCTGTACCAACGATAACATACCAAGCGTAAGTTCATTGAGAACATCTGCCCTCCCTGCCCTAAGCCCAATGCTC
TCTCCTCTTTACCTCCTCCCACCCTCTCTCTCCACTGTCTCTTAGTCTGTGTCCTCTCCCTGCTCCACATTTGTCTCCTTTGTACCTGGGGGAACAGA
GAGGAATGCCCTGACTTTTCTTTGACTGTCTGGAAAATGGGAGTCAAGTGTGGGGAGTCATTCACTTCATTTGCATGCTGCAAAACAGAGGGCGGAGG
CACCAGGGAAAGGCACTTGAATGAAGAAGGAAAATGAGAACCAGATTGTAACTTCGTCCTAATCCACCTGCCAGAACTTTCCTTCAGGTGTCACACAT
CCATTTCCATCCTAATATTAAACAATATAATGAAAGAAAGCTTTACAACAAGTCTAAATAGTTTTTATTTTCGGGCAGTCTTTTAACAAAGCAAAGCA
ACCGTGTGAGTTAGGTCACCAGAGACACCAAGCAATGGTGAAGGACCCCCTCCGCCCAATTCTCTATCCAACTAAATTTCCATGCCCAAAGTGATAGC
TATCATTTTTTCCACGGTGTATCTGCAAATCCACCCACTGTCCCGGGGTGGCTGGGAGCTTTTTAACGGGTTGAGAGTTGCTTTTTAAGGTTGTGGGT
GAGCTGAGATGGGTGACTGTGTCTTCAGGAGACACTACCATTTGGTTTGATTTTGGTTTGATTTGCAGGTGTCATCAATAAACAGAGTTCTTCGCAAC
CTGGCTAGCGAAAAGCAACAGATGGGCGCAGACGGCATGTATGATAAACTCCAGAAGTTGTAAGCAAAATAGCCCAGTATAAGCGGGAGTGCCCGTCC
ATCTTTGCTTGGGAAATCCGAGACAGATTACTGTCCGAGGGGGTCTGTACCAACGATAACATACCAAGCGTAAGTTCATTGAGAACATCTGCCCTCCC
TGCCCTAAGCCCAATGCTCTCTCCTCTTTACCTCCTCCCACCCTCTCTCTCCACTGTCTCTTAGTCTGTGTCCTCTCCCTGCTCCACATTTGTCTCCT
TTGTACCTGGGGGAACAGAGAGGAATGCCCTGACTTTTCTTTGACTGTCTGGAAAATGGGAGTCAAGTGTGGGGAGTCATTCACTTCATTTGCATGCT
GCAAAACAGAGGGCGGAGGCACCAGGGAAAGGCACTTGAATGAAGAAGGAAAATGAGAACCAGATTGTAACTTCGTCCTAATCCACCTGCCAGAACTT
TCCTTCAGGTGTCACACATCCATTTCCATCCTAATATTAAACAATATAATGAAAGAAAGCTTTACAACAAGTCTAAATAGTTTTTATTTTCGGGCAGT
CTTTTAACAAAGCAAAGCAACCGTGTGAGTTAGGTCACCAGAGACACCAAGCAATGGTGAAGGACCCCCTCCGCCCAATTCTCTATCCAACTAAATTT
CCATGCCCAAAGTGATAGCTATCATTTTTTCCACGGTGTATCTGCAAATCCACCCACTGTCCCGGGGTGGCTGGGAGCTTTTTAACGGGTTGAGAGTT
Metilação do DNA

CATAGACGTACGCGATCGATCGTACGATACGGCGATCGTACCTAGC

Promotor Exon 1 Exon 2

Metilação do DNA

S-adenosil- S-adenosil-
metionina DNA homocisteina
Metiltransferase

Citosina 5-metil Citosina

Metilação do DNA

CATAGACGTACGCGATCGATCGTACGATACGGCGATCGTACCTAGC

Promotor Exon 1 Exon 2

DNA
Metiltransferase

Promotor Exon 1 Exon 2

 Promotor Exon 1 Exon 2

DNA
Metiltransferase
Histona
Desacetilase

Proteína de ligação a citosina

metilada (MeCP2)
 Promotor Exon 1 Exon 2

FT FT
FT FT

Promotor Exon 1 Exon 2

Metilação do DNA / Desacetilação das histonas

DNA não metilado DNA metilado

Síndrome de Rett

Mutação no Gene MECP2 em Xq28

Genética e Evolução I