Genética, Epigenética e Doenças: Transcrição do Vídeo

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Questao mencionada no video (“How genotype give rise to phenotype? This is a central problem in Biology”)

https://www.youtube.com/watch?v=SHpfkNRscOc

Questões /Informações  no vídeo importantes, classificadas pelo ponto do tempo da palestra ( retirado no transcript no Youtube)
06:30
to solve, a big, a big question if you like, is where DNA, despite being the
06:34
thread of life, you can put it in a tube and gaze, gaze at it for as long as you
06:39
want and it remains utterly dead. So the question is really what does it
06:45
take to make it alive? When Craig Venter synthesized a bacterial
06:50
genome an important synthetic biology milestone, it had to be put into a living
06:55
cell before it became alive. How can one bypass that?
06:58
As the chemists say, you only really understand something if you can make it.
07:03
We can’t actually make life but it would be good to know some of the rules required
07:08
to do that.
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07:17
First of all a basic fact, genes make proteins, here is the chromosome, here is
07:23
the sequence of the genes, there is the RNA.
07:25
It encodes the sequence of the amino acids that lead to the protein that folds up to
07:30
then do all the lifelike things that are required.
07:34
But how are only the right genes expressed in a cell type?
07:36
This has been a question, a long standing question.
07:39
Do we know the answer to it? Why globin is expressed in blood cells and
07:43
keratin is expressed in skin cells, etcetera.
07:46
We, we approximate knowledge about it, but actually, there’s an enormous amount to
07:50
find out.
Matrix/DNA: Isto indica que a diversificação de células e localização de genes específicos em células especificas é mais devido a uma organização do sistema, do organismo como sistema, do que organização individual das células ou genes individuais do DNA. Portanto indica que a formula Matrix inscrita no DNA se projeta como modelo para todo o organismo, e isto deve ser feito por uma network de fótons, uma especie de aura.
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07:50
Most of the genome is actually
07:54
inaccessible. This is this gray, it’s rather difficult
07:57
to look at this picture I think because the DNA is gray and looks although it
08:01
should be in the background but this is a nucleusome, the repeating unit of the, of
08:06
the chromosome, if you like. The fundamental repeating unit.
Matrix/DNA: O autor diz que o nucleosome ( ele diz nucleusome, o que esta errado) e’ a unidade repetitiva do chromossoma, e nao sei se com isso ele quer dizer do DNA. Enquanto a Matrix/DNA sugere que a unidade fundamental do DNA e’ composta de 4 nucleotideos, dois pares laterais e verticais.
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08:08
And the DNA clings to the outside of it. And proteins that want to make genes
08:15
active, can’t actually get at the DNA properly.
08:18
So, how does the gene activation machinery gain and how does it keep access?
08:22
Again, we have some beginning answers to this, but we don’t, by any means, have a
08:28
full picture.
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Protein-coding DNA sequences are only 1%
08:32
of our genome. So, if you look at a piece of the human
08:36
genome, you see these vertical stripes correspond to the bits of this gene that
08:41
are separated from each other. In fact genes are fragmented and they are
08:47
a tiny minority of all the DNA. What is the rest of it for?
08:52
There is an enormous, there’s a vast majority that is, that we can’t explain.
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09:14
It’s particularly after the encode project which found lots of potential regulatory
09:19
sequences throughout here. So, this other DNA is doing stuff.
09:23
And perhaps, it’s doing stuff that makes for example, humans and other mammals far
09:30
more complex than yeast.
Me ocorreu uma ideia agora. Segundo a formula, o tal junk DNA são registros da Matrix do passado, de antes da abiogeneses ate’ o Big Bang. Nesse caso, são registros do ambiente externo a um sistema biológico, pois este nem existia ainda. Mas depois do inicio da abiogeneses, nestes 4 bilhões de anos, a galaxia, o universo mudou, evoluiu, ao menos ficou diferente porque se expandiu. E desta macro-dimensão devem checar fótons `a Terra, por radiação cósmica. Ora, fótons procuram e se juntam com seus vizinhos de outrora, como qualquer imigrante em pais novo. Estaria então sendo acrescentados ao DNA humano, mais exatamente entre as bases do junk DNA, os registros da Matrix a nível macrocósmico? Parece ficção, e curiosos que isto ressuscitaria o adagio antigo de que temos o universo dentro de nos.
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09:30
more complex than yeast. So finally, there are questions almost
09:37
sociological questions. Does the environment have any impact on
09:40
gene expression?
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Como surgiu “epigenetics”, qual a definicao:

10:25
The original epigenetics definition comes from Conrad Waddington, who was actually
10:31
my predecessor as Buchanan Chair, Chair, Chair of Genetics in Edinburgh.
10:36
And what he meant was in contrast to pre-formationism, but the development
10:43
proceeded by the gradual unfolding of the information in the genes, to produce the
10:46
whole organism. So, for him, how information of the genes
10:50
is read during embryo, during embryonic development to give the whole organism was
10:54
the essence of what epigenetics was about. We would now call this developmental
10:59
biology. How the genotype gives rise to the
11:01
phenotype. But it’s acquired, or a sort of, a special
11:05
status in epigenetics, really, because of this iconic picture, the epigenetic
11:11
landscape. I’m not going to dwell on this either.
11:13
Because quite honestly, having had it explained to me several times, I’m never
11:16
totally sure, exactly how this helps.
Second definition of epigenetics which is rather different has actually different
11:41
origins epistemological origins. How characteristics are inherited across
11:48
cells or organism generations without changes in the DNA, its sequence, itself.
11:53
An example of this is this cat, the so-called tortoise shell cat, or calico
11:58
cat, in, in, in the US, which has these patches of fur.
12:02
It has two x chromosomes. One of them has a gene that gives black
12:06
fur, the other one has a gene that gives orange fur, and cells early in
12:11
development, inactivate one or the other of those chromosomes for, for reasons we
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don’t, which I will, I will come back to actually, a little bit later.
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And you get a patch of skin because the cell that originally inactivated the
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orange fur gene gave rise when it divided to cells that did exactly the same thing.
12:28
So, that was inherited. All the gene or the, the DNA is still
12:32
there in these cells, in, in the orange ones, and the black ones, but there is
12:37
difference that is inherited and that’s epigenetic according to this definition.
12:43
So, heritable traits of this kind might be influenced by the environment.
12:48
And this is sort of revitalized that an ancient argument about nature versus
12:55
nurture, where nature is genetics, the idea that we’re, our genes are, are in
12:59
control and nurture is the opposite, the idea that our environment determines who
13:03
we are.Of course, it’s a mixture of both but
13:07
epigenetics has given a, a, a new lease of life to the nurture argument.
13:12
And so, one can see articles such as this and there are many examples I could have
13:17
chosen why your DNA isn’t your destiny, the new science of epigenetics reveals how
13:23
choices you make can change your genes and those of your kids.
13:27
Now, I’m not an expert on some of the epidemiology behind this, but the, the
13:32
molecular biology, in my opinion, is far less convincing than it is for other
13:35
aspects of epigenetics. It is, however, an extremely interesting
13:40
idea, that the environment can give rise to changes that get passed on, but it is
13:45
systematically overstated in a lot of places one finds it described.
13:49
So, one has to be circumspect about the, this kind of argument in my opinion.
13:54
There are couple of excellent examples in plants, in worms where immune, immunity is
14:00
involved, but some of the more sociological aspects, in my opinion,
14:05
require further evidence. So, I’m sticking with this as my example
14:09
of heritable epigenetics. It’s closer to the molecular biology we
14:12
actually understand. So, Epigenetics 3, biological significance…
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17:04
disease. So, epigenetics then embraces key unsolved
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problems in Biology, how, how the genotype give rise to phenotype, that’s the
17:12
Waddington one, how traits are inherited across cell or organism generations
17:17
without changes in the DNA sequence and how structural adaptation of the genome
17:21
facilitates gene activity programs. As far as I’m concerned, this is not a
17:26
word one needs to dwell on with sort of almost a theological interest about what
17:34
it means.
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17:39
And I, I like to think of it as how the genome is organized and managed to make
17:43
DNA if you like, come alive.
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Sobre CG islands:
 In fact, for a long time, we were used to
26:00
the fact that CG islands existed, but we didn’t really know what they were for.
26:04
And, and actually, one almost forgot to ask, well, they’re always there, what are
26:08
they for? In fact, it now seems very likely that
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they are platforms to set up appropriate genome structures at gene promoters.
26:16
Very important function. And there are other proteins that bind CG,
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that recruit other things to them, and this is a very, a rapidly growing area.
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