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INTRODUÇÃO A GENÔMICA NUTRICIONAL
Augusto Schneider Faculdade de Nutrição
Universidade Federal de Pelotas
CRONOGRAMA
AVALIAÇÕES: 2 Provas + 1 Seminário
21/03 – Introdução a genômica nutricional 28/03 - Organização do genoma e variação individual 04/04 - Controle da expressão gênica e síntese de proteínas 11/04 - Os genes nas populações 18/04 – Feriado 25/04 - Bioinformática aplicada a genômica nutricional 02/05 – Ponto facultativo 09/05 - Técnicas em genômica nutricional 16/05 – Aula prática 23/05 – Prova 1 30/05 - Nutrigenética 06/06 - Nutrientes e expressão gênica 13/06 - Nutrição materna e mecanismos epigenéticos 20/06 – Seminários 27/06 – Seminários 04/07 - Seminarios 11/07 – Prova 2 18/07 – Optativa 25/07 – Exame
OBJETIVOS DA DISCIPLINA
Introduzir conceitos básicos, termos e técnicas Permitir o entendimento desta ferramenta de estudo Prover o entendimento de como os alimentos podem afetar a expressão de genes Prover conhecimento sobre como a variação genética individual afeta o metabolismo de nutrientes e predispõe a doenças Permitir o entendimento de novos serviços de avaliação genética para aconselhamento nutricional
Estudo do efeito de componentes bioativos da dieta na expressão de genes e consequências nas funções bioquímicas/fisiológicas.
Estudo do efeito da variação genética individual na resposta a dieta e a nutrição.
CONCEITO
CONCEITO
Pesquisa/descoberta de novos nutrientes funcionais
Serviço ao Público/Aconselhamento nutricional
Troca na sequência normal de nucleotídeos Pode levar a uma modificação na função da proteína
SNP (snips) – Single nucleotide polymorphism Quando esta troca aparece em mais 1% da população
NUTRIGENÉTICA
Não confundir nutrigenômica/nutrigenética com epigenética
O que é epigenética?
O que tem haver com nutrição?
EPIGENÉTICA
EPIGENÉTICA
THE REGULATION OF CHROMATIN STRUCTURE
The DNA in eucaryotes is tightly bound to an equal mass of histones, which formrepeated arrays of DNA-protein particles called nucleosomes. The nucleosome is com-posed of an octameric core of histone proteins around which the DNA double helix iswrapped. Nucleosomes are spaced at interuals of about 200 nucleotide pairs, and theyare usually packed together (with the aid of histone Hl molecules) into quasi-regulararrays to form a 30-nm chromatin fiber. Despite the high degree of compaction inchromatin, its structure must be highly dynamic to allow access to the DNA. There issome spontaneous DNA unwrapping and rewrapping in the nucleosome itself; how'euer, the general strategy for reuersibly changing local chromatin structure featuresATP-driuen chromatin remodeling complexes. Cells contain a large set of such com-plexes, which are targeted to speciflc regions of chromatin at appropriate times. Theremodeling complexes collaborate with histone chaperones to allow nucleosome coresto be repositioned, reconstituted with dffirent histones, or completely remoued toexpose the underlying DNA.
THE REGULATION OF CHROM IN STRUCTUREHaving described how DNA is packaged into nucleosomes to create a chromatinfiber, we now turn to the mechanisms that create different chromatin structuresin different regions of a cell's genome. We now know that mechanisms of this typeare used to control many genes in eucaryotes. Most importantly, certain types ofchromatin structure can be inherited; that is, the structure can be directly passeddonm from a cell to its decendents. Because the cell memory that results is basedon an inherited protein structure rather than on a change in DNA sequence, thisis a form of epigenetic inheritance. The prefix epl is Greek for "on"; this is appro-priate, because epigenetics represents a form of inheritance that is superimposedon the genetic inheritance based on DNA (Figure,t-35).
In Chapter 7, we shall introduce the many different ways in which theexpression of genes is regulated. There we discuss epigenetic inheritance indetail and present several distinct mechanisms that can produce it. Here, we areconcerned with only one, that based on chromatin structure. We begin this sec-tion with an introduction to inherited chromatin structures and then describethe basis for them-the covalent modification of histones in nucleosomes. Weshall see that these modifications serve as recognition sites for protein modulesthat bring specific protein complexes to the appropriate regions of chromatin,thereby producing specific effects on gene expression or inducing other biolog-ical functions. Through such mechanisms, chromatin structure plays a centralrole in the development, growth, and maintenance of eucaryotic organisms'including ourselves.
GENETIC INHERITANCEgene X on
I orun seeuerucrI CHANGE
EPIGENETIC INHERITANCEgene Y on
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gene X ofl CIITI!oene Y of f
MULTTPLTCATTON OF SOMATTC CELLS /\
II
219
Figure 4-35 A comparison of geneticinheritance with an epigeneticinheritance based on chromatinstructures. Genetic inheritance is basedon the direct inheritance of DNAnucleotide sequences during DNAreplication. DNA sequence changes arenot only transmitted faithful ly from asomatic cel l to al l of i ts descendents, butalso through germ cel ls from onegeneration to the next.The f ield ofgenetics, reviewed in Chapter 8, is basedon the inheritance of these changesbetween generations. The type ofepigenetic inheritance shown here isbased on other molecules bound to theDNA, and i t is therefore less permanentthan a change in DNA sequence; inpart icular, epigenetic information isusually (but not always) erased duringthe formation of eggs and sPerm.
Only one epigenetic mechanism, thatbased on an inheritance of chromatinstructures, is discussed in this chapter.Other epigenetic mechanisms arepresented in Chapter 7, which focuses onthe control of gene expression (seeFigure 7-86).
gene X off *E* i lgene Y off
:ililiii:li:i.t, tiiilillii*:it:]it::]iltl::.lul iilisi:i:liitl
gene X off
PRODUCTION OF GERM CELLS
EPIGENÉTICA
Restrição alimentar durante a gestação
Filhos nascem pequenos e com maior propensão na vida adulta a: • Obesidade • Diabetes • Disfunção renal
Funciona como um mecanismo de adaptação ao que pode ocorrer na vida adulta
Programação fetal