02_Pereira_RW_SBG_2011
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Transcript of 02_Pereira_RW_SBG_2011
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Sequenciamento de ácidos nucleicos em larga escala como novo paradigma para
geração de conhecimento
Prof. Dr. Rinaldo Wellerson PereiraPrograma de Pós Graduação em Ciências
Genômicas e Biotecnologia
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Contatos
https://www.facebook.com/pages/Genética-Prof-Rinaldo-Pereira/173846522641806
http://rinaldogenetica.com
rinaldo.ucb rinaldo_pereira
https://www.facebook.com/pages/Ci%C3%AAncias-Gen%C3%B4micas-UCB-Bras%C3%ADlia/199850806721852
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Planejamento
• Dia 01/09/11 – Sequenciamento de Genomas– Variabilidade de Sequência– Variabilidade de Estrutura– Diagnóstico – Prognóstico– História de Populações
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Sequenciamento de GenomasPré-NGS
SequenciamentoClone by Clone
SequenciamentoWhole Genome Shotgun
ABI 3700 ABI 3730
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Sacharomyces cerevisae25/10/1996
Caenorhabditis elegans
11/12/1998
Drosophila melanogaster24/03/2000
Arabidopsis thaliana
14/12/2000
Homo sapiens sapiens15/02/2001 e 16/02/2001
Haemophilusinfluenza
28/07/1995
Pan troglodytes01/09/2005
Mus muscullus
05/12/2002
Rattus novergicus
01/04/2005
Gallus gallus
09/12/2004
Cannis familiaris
05/12/2005
Apis mellifera
26/10/2006
Monodelphisdomestica10/05/2007
Tetraedon Nigrovirids21/10/2004
Finalização doGenoma Humano
Macaca mulatta
13/04/2007
ZeaMays
20/11/2009
Bostaurus
24/04/2009
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O que se extrai de um genoma?
A ponta do Iceberg! O início de uma longa jornada!
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Cromatina
mRNA ncRNA
Proteínas
Variação Normal ou PatológicaAmbiente
Variação em sequência Variação estrutural Variação química na cromatina
Epigenômica
Genômica
Transcritômica
Proteômica
Dogma Central
Edição de RNA
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Sequenciamentos de Genomas na era NGS
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Sequenciando Genomas para Investigar Variabilidade
• SNVs – Single nucleotide variants
• SNPs – Single nucleotide polymorphisms
• CNVs – Copy number variants
• CNPs – Copy number polymorphisms
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http://jimwatsonsequence.cshl.edu/cgi-perl/gbrowse/jwsequence/
Sequenciado com 454
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Genomas Individuais
Bentley et al.
Wang et al.
http://yh.genomics.org.cn/
http://www.illumina.com/HumanGenome/
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Explosão de Genomas Individuais
2001
2004
2007
2008
20092010
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Mais e mais Genomas Individuais
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NGS e Estudos de Associação
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Published Genome-Wide Associations through 03/2011, 1,319 published GWA at p≤5x10-8 for 221 traits
NHGRI GWA Catalogwww.genome.gov/GWAStudies
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2005
2006
2007
2008
2009
2010
2011
0
100
200
300
400
500
600
700
800
900
1000
Published GWA Reports, 2005 – 6/2011To
tal N
umbe
r of P
ublic
ation
s
951
Calendar QuarterThrough 9/30/10 postings
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Missing Heritability e o sequenciamento de genomas individuais
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Doenças Mendelianas
• Doenças muito raras não tem número de famílias suficiente para estudos de ligação ou mapeamento por homozigozidade
• Doenças Mendelianas esporádicas por mutações de novo
• Heterogeinidade de loco• Heterogeinidade de fenótipo
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Exoma
• Estima-se que 90% das doenças mendelianas tem como causa variações em exons
• Exoma é o sequenciamento de todos ou quase todos exons em uma amostra
• O primeiro passo é separar os exons do restante do DNA
• Estima-se o exoma humano em 35 a 40 Mb (aproximadamente 1 % do genoma total)
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Captura de Exons
Captura de 180.000 exons codificantesCaptura de 541 exons de micro RNAs
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Sequenciamento de Genomas como método de diagnóstico
• Exoma
• Genoma Total
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Consulta em 05/07/2011Consulta em 01/09/2011
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Antropologia Molecular
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Next Generation Sequencing amplia possibilidades de melhor caracterização da variação estrutural em
genomas
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NGS Câncer - Sequenciamento
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Por hoje Fechamos!!
• Nos vemos amanhã!