thank you for listening to my talk today because I know that you’d all rather be
because I know that you’d all rather be
because I know that you’d all rather be having sex the average healthy person
having sex the average healthy person
having sex the average healthy person thinks about sex every day did you know
thinks about sex every day did you know
thinks about sex every day did you know that one reason that men and women
that one reason that men and women
that one reason that men and women involved and exist is to have sex and
involved and exist is to have sex and
involved and exist is to have sex and we’re not the only ones thinking about
we’re not the only ones thinking about
we’re not the only ones thinking about it but while you’re lying in bed next to
it but while you’re lying in bed next to
it but while you’re lying in bed next to your partner sweaty and exhausted
your partner sweaty and exhausted
your partner sweaty and exhausted wrapped in red satin sheets listening to
wrapped in red satin sheets listening to
wrapped in red satin sheets listening to Kenny G have you ever pondered why
fundamentally sex is how mums and dads
fundamentally sex is how mums and dads contribute their genes to their
contribute their genes to their
contribute their genes to their offspring so for most of the 19,000
offspring so for most of the 19,000
offspring so for most of the 19,000 genes embedded in our chromosomes we
genes embedded in our chromosomes we
genes embedded in our chromosomes we have two copies one that we inherit from
have two copies one that we inherit from
have two copies one that we inherit from our mom and one that we inherit from our
our mom and one that we inherit from our
our mom and one that we inherit from our dad this is the recipe for life but why
dad this is the recipe for life but why
dad this is the recipe for life but why does the recipe call for two helpings of
does the recipe call for two helpings of
does the recipe call for two helpings of most genes one reason is that it’s
most genes one reason is that it’s
most genes one reason is that it’s always good to have a backup if one gene
always good to have a backup if one gene
always good to have a backup if one gene copy has a mutation the other healthy
copy has a mutation the other healthy
copy has a mutation the other healthy copy can compensate and we all have some
copy can compensate and we all have some
copy can compensate and we all have some intuition for this because it’s common
intuition for this because it’s common
intuition for this because it’s common knowledge that you shouldn’t marry and
knowledge that you shouldn’t marry and
knowledge that you shouldn’t marry and have children with your sister or
have children with your sister or
have children with your sister or brother no matter how wonderful they may
brother no matter how wonderful they may
brother no matter how wonderful they may be people who are closely related to
be people who are closely related to
be people who are closely related to share many of the same mutations in
share many of the same mutations in
share many of the same mutations in their genes and so if they have kids
their genes and so if they have kids
their genes and so if they have kids together the kids have a higher risk for
together the kids have a higher risk for
together the kids have a higher risk for having the same mutation in both copies
having the same mutation in both copies
having the same mutation in both copies no healthy
no healthy
no healthy copy and so they have a higher risk for
copy and so they have a higher risk for
copy and so they have a higher risk for developing a genetic disorder so one
developing a genetic disorder so one
developing a genetic disorder so one reason that we have sex is to mix the
reason that we have sex is to mix the
reason that we have sex is to mix the genes from different and ideally
genes from different and ideally
genes from different and ideally unrelated individuals but that’s not the
unrelated individuals but that’s not the
unrelated individuals but that’s not the whole story
whole story
whole story in the 1980s scientists learned how to
in the 1980s scientists learned how to
in the 1980s scientists learned how to take all the fun out of making babies at
take all the fun out of making babies at
take all the fun out of making babies at least for mice when the sperm meets the
least for mice when the sperm meets the
least for mice when the sperm meets the egg it forms a zygote that contains the
egg it forms a zygote that contains the
egg it forms a zygote that contains the set of genes you get from mom and the
set of genes you get from mom and the
set of genes you get from mom and the set of genes you get from dad and the
set of genes you get from dad and the
set of genes you get from dad and the scientists were working in the lab and
scientists were working in the lab and
scientists were working in the lab and they developed these tiny needles and
they developed these tiny needles and
they developed these tiny needles and they went into the zygote and they
they went into the zygote and they
they went into the zygote and they sucked out the genes that came from the
sucked out the genes that came from the
sucked out the genes that came from the dad and they injected in a second copy
dad and they injected in a second copy
dad and they injected in a second copy of genes from mum so the embryos
of genes from mum so the embryos
of genes from mum so the embryos effectively had two mothers no father
effectively had two mothers no father
effectively had two mothers no father involved and they also engineered the
involved and they also engineered the
involved and they also engineered the opposite situation where they had
opposite situation where they had
opposite situation where they had embryos that had two sets of genes from
embryos that had two sets of genes from
embryos that had two sets of genes from dad and no mother involved what do you
dad and no mother involved what do you
dad and no mother involved what do you think happened
they died even though they had the
they died even though they had the normal set of gene copies only embryos
normal set of gene copies only embryos
normal set of gene copies only embryos that were engineered with a set of gene
that were engineered with a set of gene
that were engineered with a set of gene copies from mom and a set of gene copies
copies from mom and a set of gene copies
copies from mom and a set of gene copies from dad generated mice that survived
from dad generated mice that survived
from dad generated mice that survived and the experiment revealed that the
and the experiment revealed that the
and the experiment revealed that the genes we get from mom and dad are
genes we get from mom and dad are
genes we get from mom and dad are somehow different they’re not just
somehow different they’re not just
somehow different they’re not just backup copies for each other the
backup copies for each other the
backup copies for each other the difference turned out to involve a
difference turned out to involve a
difference turned out to involve a special kind of gene in our genome
special kind of gene in our genome
special kind of gene in our genome called imprinted genes now imprinted
called imprinted genes now imprinted
called imprinted genes now imprinted genes are distinguished by the fact that
genes are distinguished by the fact that
genes are distinguished by the fact that moms and dads stick chemical marks to
moms and dads stick chemical marks to
moms and dads stick chemical marks to them in the egg and the sperm and those
them in the egg and the sperm and those
them in the egg and the sperm and those chemical marks are inherited by the kids
chemical marks are inherited by the kids
chemical marks are inherited by the kids and they silence the genes in the kid
and they silence the genes in the kid
and they silence the genes in the kid but mums and dads put those marks on
but mums and dads put those marks on
but mums and dads put those marks on different genes and so as a consequence
different genes and so as a consequence
different genes and so as a consequence some genes silenced the copy from dad
some genes silenced the copy from dad
some genes silenced the copy from dad and Express the copy from mom and the
and Express the copy from mom and the
and Express the copy from mom and the kids and other genes silenced the copy
kids and other genes silenced the copy
kids and other genes silenced the copy from mom but expressed the copy from dad
from mom but expressed the copy from dad
from mom but expressed the copy from dad you may be deeply disturbed by the idea
you may be deeply disturbed by the idea
you may be deeply disturbed by the idea that your parents sent you secret
that your parents sent you secret
that your parents sent you secret messages that are stuck to your genes
messages that are stuck to your genes
messages that are stuck to your genes but I’m just getting started
the scientists again engineered cells
the scientists again engineered cells with genes from two moms and cells with
with genes from two moms and cells with
with genes from two moms and cells with genes from two dads and they mix them
genes from two dads and they mix them
genes from two dads and they mix them together with normal cells so that the
together with normal cells so that the
together with normal cells so that the embryos would live longer and what they
embryos would live longer and what they
embryos would live longer and what they discovered was amazing the embryos with
discovered was amazing the embryos with
discovered was amazing the embryos with cells with two sets of genes from mom
cells with two sets of genes from mom
cells with two sets of genes from mom developed small bodies but very large
developed small bodies but very large
developed small bodies but very large brains
and the embryos that were engineered
and the embryos that were engineered with cells that end that had a set of
with cells that end that had a set of
with cells that end that had a set of genes from only dads had the exact
genes from only dads had the exact
genes from only dads had the exact opposite phenotype they had large bodies
opposite phenotype they had large bodies
opposite phenotype they had large bodies and relatively small brains so you may
and relatively small brains so you may
and relatively small brains so you may not be surprised by this but what it
not be surprised by this but what it
not be surprised by this but what it revealed is that the imprinted genes we
revealed is that the imprinted genes we
revealed is that the imprinted genes we get from mom and dad have very different
get from mom and dad have very different
get from mom and dad have very different effects on offspring brain and body
effects on offspring brain and body
effects on offspring brain and body development so mom and dad moms and dads
development so mom and dad moms and dads
development so mom and dad moms and dads send us different messages through these
send us different messages through these
send us different messages through these imprinted genes but while imported genes
imprinted genes but while imported genes
imprinted genes but while imported genes are fascinating they’re also rare only
are fascinating they’re also rare only
are fascinating they’re also rare only about 1% of the 19,000 genes in our
about 1% of the 19,000 genes in our
about 1% of the 19,000 genes in our genome are imprinted and the researchers
genome are imprinted and the researchers
genome are imprinted and the researchers in my lab were left with the question
in my lab were left with the question
in my lab were left with the question what’s the story with the other 99% of
what’s the story with the other 99% of
what’s the story with the other 99% of our genes do they have two copies just
our genes do they have two copies just
our genes do they have two copies just to have a backup is that the whole story
to have a backup is that the whole story
to have a backup is that the whole story is it time to roll over turn out the
is it time to roll over turn out the
is it time to roll over turn out the light and go to sleep not yet and this
light and go to sleep not yet and this
light and go to sleep not yet and this part of the talk is complicated but you
part of the talk is complicated but you
part of the talk is complicated but you know it’s not the kamasutra
when the genes in our DNA are expressed
when the genes in our DNA are expressed they make a molecule called RNA RNA
they make a molecule called RNA RNA
they make a molecule called RNA RNA makes protein and proteins build our
makes protein and proteins build our
makes protein and proteins build our cells we can measure RNA sometimes when
cells we can measure RNA sometimes when
cells we can measure RNA sometimes when our genes are activated they make a lot
our genes are activated they make a lot
our genes are activated they make a lot of RNA and sometimes they make just a
of RNA and sometimes they make just a
of RNA and sometimes they make just a little now imagine that we clone a whole
little now imagine that we clone a whole
little now imagine that we clone a whole bunch of nerds
and we dissect out a piece of brain
and we dissect out a piece of brain tissue from each nerd and measure the
tissue from each nerd and measure the
tissue from each nerd and measure the activity of the genes in that brain
activity of the genes in that brain
activity of the genes in that brain tissue for given gene and some
tissue for given gene and some
tissue for given gene and some individuals each activity level will be
individuals each activity level will be
individuals each activity level will be high in others it will be low there will
high in others it will be low there will
high in others it will be low there will be just this natural variation across
be just this natural variation across
be just this natural variation across different individuals because of natural
different individuals because of natural
different individuals because of natural variation in their physiology and
variation in their physiology and
variation in their physiology and variation and how we dissected out that
variation and how we dissected out that
variation and how we dissected out that piece of tissue but now we drill down to
piece of tissue but now we drill down to
piece of tissue but now we drill down to the level of the mum and dad’s gene
the level of the mum and dad’s gene
the level of the mum and dad’s gene copies and we expect that the two copies
copies and we expect that the two copies
copies and we expect that the two copies will go up and down together in their
will go up and down together in their
will go up and down together in their activity because they’re just backup
activity because they’re just backup
activity because they’re just backup copies of one another expressed and
copies of one another expressed and
copies of one another expressed and regulated in the exact same way but what
regulated in the exact same way but what
regulated in the exact same way but what if we discover genes where that’s not
if we discover genes where that’s not
if we discover genes where that’s not the case and they express the two copies
the case and they express the two copies
the case and they express the two copies differently well that would exceed are
differently well that would exceed are
differently well that would exceed are not just backup copies of each other
not just backup copies of each other
not just backup copies of each other that maybe they’re doing different
that maybe they’re doing different
that maybe they’re doing different things so we did this experiment for
things so we did this experiment for
things so we did this experiment for each of the 19,000 genes in the genome
each of the 19,000 genes in the genome
each of the 19,000 genes in the genome in mice and we found genes that express
in mice and we found genes that express
in mice and we found genes that express mum and dad’s copy the same way they
mum and dad’s copy the same way they
mum and dad’s copy the same way they were highly correlated like this gene as
were highly correlated like this gene as
were highly correlated like this gene as though they’re acting as backup copies
though they’re acting as backup copies
though they’re acting as backup copies for each other but we also discovered
for each other but we also discovered
for each other but we also discovered hundreds of genes where that was not the
hundreds of genes where that was not the
hundreds of genes where that was not the case like this gene a door to B when
case like this gene a door to B when
case like this gene a door to B when mom’s copy increases its activity dad’s
mom’s copy increases its activity dad’s
mom’s copy increases its activity dad’s copy decreases its activity they’re
copy decreases its activity they’re
copy decreases its activity they’re negatively correlated acting
negatively correlated acting
negatively correlated acting antagonistically to each other clearly
antagonistically to each other clearly
antagonistically to each other clearly doing different things and the story got
doing different things and the story got
doing different things and the story got even more interesting when we started to
even more interesting when we started to
even more interesting when we started to measure these things at different ages
measure these things at different ages
measure these things at different ages in the adult brain ten percent of genes
in the adult brain ten percent of genes
in the adult brain ten percent of genes expressed mom and dad’s gene copies
expressed mom and dad’s gene copies
expressed mom and dad’s gene copies differently but in the developing
differently but in the developing
differently but in the developing newborn brain over eighty five percent
newborn brain over eighty five percent
newborn brain over eighty five percent of genes expressed the two copies
of genes expressed the two copies
of genes expressed the two copies differently
differently
differently it was as though each gene copy had its
it was as though each gene copy had its
it was as though each gene copy had its own unique role to play in building the
own unique role to play in building the
own unique role to play in building the developing brain holy crap
developing brain holy crap
developing brain holy crap there was no time left for sex we had to
there was no time left for sex we had to
there was no time left for sex we had to like get into the lab and do some
like get into the lab and do some
like get into the lab and do some serious experiments because this could
serious experiments because this could
serious experiments because this could really change how we think about how our
really change how we think about how our
really change how we think about how our genes make us who we are over the past
genes make us who we are over the past
genes make us who we are over the past several decades we have developed new
several decades we have developed new
several decades we have developed new technologies that can routinely sequence
technologies that can routinely sequence
technologies that can routinely sequence our genomes and analyze our genes and
our genomes and analyze our genes and
our genomes and analyze our genes and we’ve learned a whole bunch of
we’ve learned a whole bunch of
we’ve learned a whole bunch of surprising things we’ve learned that all
surprising things we’ve learned that all
surprising things we’ve learned that all of us have bonafide disease-causing
of us have bonafide disease-causing
of us have bonafide disease-causing mutations in our genome about 400
mutations in our genome about 400
mutations in our genome about 400 damaging mutations on average to lethal
damaging mutations on average to lethal
damaging mutations on average to lethal mutations but I feel fine and you guys
mutations but I feel fine and you guys
mutations but I feel fine and you guys all look great
all look great
all look great so for reasons that we don’t fully
so for reasons that we don’t fully
so for reasons that we don’t fully understand some of us get sick and some
understand some of us get sick and some
understand some of us get sick and some of us don’t the other thing that we’ve
of us don’t the other thing that we’ve
of us don’t the other thing that we’ve learned is that the mutations in our
learned is that the mutations in our
learned is that the mutations in our genes that influence our risk for
genes that influence our risk for
genes that influence our risk for disease are typically present in just
disease are typically present in just
disease are typically present in just one gene copy not both
one gene copy not both
one gene copy not both for example paternal age has emerged as
for example paternal age has emerged as
for example paternal age has emerged as an important risk factor for a lot of
an important risk factor for a lot of
an important risk factor for a lot of different disorders like autism and one
different disorders like autism and one
different disorders like autism and one reason is that fathers are constantly
reason is that fathers are constantly
reason is that fathers are constantly generating new sperm and they accumulate
generating new sperm and they accumulate
generating new sperm and they accumulate more and more mutations in the genes in
more and more mutations in the genes in
more and more mutations in the genes in the sperm as they get older and older
the sperm as they get older and older
the sperm as they get older and older about two new mutations per year and
about two new mutations per year and
about two new mutations per year and those mutations are inherited by the
those mutations are inherited by the
those mutations are inherited by the kids in their dads gene copies the mom’s
kids in their dads gene copies the mom’s
kids in their dads gene copies the mom’s copies should act as a backup but we’ve
copies should act as a backup but we’ve
copies should act as a backup but we’ve just learned that in many cases the mom
just learned that in many cases the mom
just learned that in many cases the mom and dad copies are expressed differently
and dad copies are expressed differently
and dad copies are expressed differently so how does this actually play out we
so how does this actually play out we
so how does this actually play out we wanted to know and so we engineered mice
wanted to know and so we engineered mice
wanted to know and so we engineered mice with a mutated gene copy and a healthy
with a mutated gene copy and a healthy
with a mutated gene copy and a healthy gene copy and we looked at how they’re
gene copy and we looked at how they’re
gene copy and we looked at how they’re expressed in the brain cells of the lab
expressed in the brain cells of the lab
expressed in the brain cells of the lab ones we discovered cells that Express
ones we discovered cells that Express
ones we discovered cells that Express both the healthy copy and the mutated
both the healthy copy and the mutated
both the healthy copy and the mutated copy
copy
copy kind of like we expected so there’s a
kind of like we expected so there’s a
kind of like we expected so there’s a backup healthy copy there but we also
backup healthy copy there but we also
backup healthy copy there but we also discovered cells that were only
discovered cells that were only
discovered cells that were only expressing the healthy copy which was
expressing the healthy copy which was
expressing the healthy copy which was very surprising but more alarmingly we
very surprising but more alarmingly we
very surprising but more alarmingly we found cells that only expressed the
found cells that only expressed the
found cells that only expressed the mutated gene copy the cells that
mutated gene copy the cells that
mutated gene copy the cells that preferentially expressed mutated gene
preferentially expressed mutated gene
preferentially expressed mutated gene copies contribute to our risk for
copies contribute to our risk for
copies contribute to our risk for disease if they do this paints a very
disease if they do this paints a very
disease if they do this paints a very different picture of disease but we
different picture of disease but we
different picture of disease but we don’t know right now it’s just an idea
don’t know right now it’s just an idea
don’t know right now it’s just an idea and there are a whole bunch of questions
and there are a whole bunch of questions
and there are a whole bunch of questions that remain most of what I’ve talked
that remain most of what I’ve talked
that remain most of what I’ve talked about we did in lab mice but you may be
about we did in lab mice but you may be
about we did in lab mice but you may be wondering what’s happening in you you
wondering what’s happening in you you
wondering what’s happening in you you may be wondering about how your parents
may be wondering about how your parents
may be wondering about how your parents genes are expressed in you and if you
genes are expressed in you and if you
genes are expressed in you and if you are a parent then maybe you’re thinking
are a parent then maybe you’re thinking
are a parent then maybe you’re thinking about how your genes are expressed in
about how your genes are expressed in
about how your genes are expressed in your kids maybe they have really
your kids maybe they have really
your kids maybe they have really annoying habits like their father and
annoying habits like their father and
annoying habits like their father and now you’re thinking they must express a
now you’re thinking they must express a
now you’re thinking they must express a lot of his gene copies we also wanted to
lot of his gene copies we also wanted to
lot of his gene copies we also wanted to know the answer to this and so we
know the answer to this and so we
know the answer to this and so we developed a staining method that we
developed a staining method that we
developed a staining method that we could use in postmortem human brain
could use in postmortem human brain
could use in postmortem human brain tissue to look at the activity of the
tissue to look at the activity of the
tissue to look at the activity of the two copies we get from mom and dad the
two copies we get from mom and dad the
two copies we get from mom and dad the staining method reveals the individual
staining method reveals the individual
staining method reveals the individual brain cells in blue and it reveals the
brain cells in blue and it reveals the
brain cells in blue and it reveals the activity of the two copies of a gene in
activity of the two copies of a gene in
activity of the two copies of a gene in red we can’t tell which copy is mutated
red we can’t tell which copy is mutated
red we can’t tell which copy is mutated or healthy yet and we can’t top kill we
or healthy yet and we can’t top kill we
or healthy yet and we can’t top kill we can’t tell which one comes from mom and
can’t tell which one comes from mom and
can’t tell which one comes from mom and which one comes from dad but we can see
which one comes from dad but we can see
which one comes from dad but we can see for each cell whether it’s expressing
for each cell whether it’s expressing
for each cell whether it’s expressing both copies equally or differently we
both copies equally or differently we
both copies equally or differently we found genes like this one that expresses
found genes like this one that expresses
found genes like this one that expresses both the mom and the dads copy equally
both the mom and the dads copy equally
both the mom and the dads copy equally in human brain cells so there’s a back
in human brain cells so there’s a back
in human brain cells so there’s a back up copy there but we also discovered
up copy there but we also discovered
up copy there but we also discovered genes like these ones
genes like these ones
genes like these ones Huntington which is linked to
Huntington which is linked to
Huntington which is linked to Huntington’s disease and a gene called
Huntington’s disease and a gene called
Huntington’s disease and a gene called death one that’s linked to autism they
death one that’s linked to autism they
death one that’s linked to autism they are clearly expressing there are two
are clearly expressing there are two
are clearly expressing there are two copies differently and we found brain
copies differently and we found brain
copies differently and we found brain cells that have only one active gene
cells that have only one active gene
cells that have only one active gene copy so like mice we also frequently
copy so like mice we also frequently
copy so like mice we also frequently express our mom and dad’s gene copies
express our mom and dad’s gene copies
express our mom and dad’s gene copies differently and this means we may not
differently and this means we may not
differently and this means we may not fully understand why we have sex and
fully understand why we have sex and
fully understand why we have sex and contribute to copies of most genes to
contribute to copies of most genes to
contribute to copies of most genes to our kids research over the past several
our kids research over the past several
our kids research over the past several decades has taught us an incredible
decades has taught us an incredible
decades has taught us an incredible amount about how our genes make us who
amount about how our genes make us who
amount about how our genes make us who we are and by gaining a deeper a deeper
we are and by gaining a deeper a deeper
we are and by gaining a deeper a deeper understanding of our genes or gaining a
understanding of our genes or gaining a
understanding of our genes or gaining a deeper understanding of disease we’re
deeper understanding of disease we’re
deeper understanding of disease we’re learning how to make better therapies
learning how to make better therapies
learning how to make better therapies better medicines but there are lots of
better medicines but there are lots of
better medicines but there are lots of mysteries that remain we think that
mysteries that remain we think that
mysteries that remain we think that we’ve discovered something fundamentally
we’ve discovered something fundamentally
we’ve discovered something fundamentally new by studying the activity of our
new by studying the activity of our
new by studying the activity of our genes at the level of the two copies we
genes at the level of the two copies we
genes at the level of the two copies we get from mom and dad and we were
get from mom and dad and we were
get from mom and dad and we were surprised to find that there are genes
surprised to find that there are genes
surprised to find that there are genes that we know caused disease and people
that we know caused disease and people
that we know caused disease and people that express their two copies
that express their two copies
that express their two copies differently we found cells that
differently we found cells that
differently we found cells that frequently Express mom and dad’s copies
frequently Express mom and dad’s copies
frequently Express mom and dad’s copies differently mutated and healthy gene
differently mutated and healthy gene
differently mutated and healthy gene copies differently why do these effects
copies differently why do these effects
copies differently why do these effects play some special role in shaping the
play some special role in shaping the
play some special role in shaping the function of our brain do they shape our
function of our brain do they shape our
function of our brain do they shape our risks for disease we feel like explorers
risks for disease we feel like explorers
risks for disease we feel like explorers on the edge of a new frontier and we’re
on the edge of a new frontier and we’re
on the edge of a new frontier and we’re really excited to find out what we’re
really excited to find out what we’re
really excited to find out what we’re going to learn we may discover that your
going to learn we may discover that your
going to learn we may discover that your parents always have the last word
parents always have the last word
parents always have the last word thank you
thank you
thank you [Applause]
”
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