I’m Dr. Neville Sanjana, human geneticist.

Today I’ll be taking your questions from Twitter.

This is Genetics Support.

[upbeat music]

@SortOfKnownO asks,

Someone explain Lenny Kravitz to me, please.

I’d like to understand how his genes work.

How is he still this hot?

I’m not sure there’s a gene for hot,

but most complex traits are not due to just one gene,

they’re due to many genes.

All of us inherit part of our genome from our mom

and part of our genome from our dad.

And Lenny Kravitz has a pretty diverse ancestry.

He has Russian-Jewish ancestry from his father’s side,

he has Afro-Caribbean ancestry from his mother’s side.

The genes that control our immune system

are amongst the most variable genes in the human genome.

Maybe the secret to Lenny’s youthfulness

is that he inherited a diverse set of immune genes.

@NoTrafficInLA asks, can they DNA test ashes?

Unfortunately, no.

DNA breaks down at temperatures above 400 degrees Fahrenheit

and cremation happens at very high temperatures,

like 1500 degrees or 2000 degrees Fahrenheit.

But at ambient temperature, the story is different.

DNA is very stable.

In fact, the Nobel Prize in 2022 was given out

to Svante Paabo for sequencing

and reconstructing the genome of a Neanderthal.

@syssecserv asks, I personally find it hard to believe

that all human beings who have blue eyes are descendants

of one human being who had a genetic mutation.

All current evidence points to an event

about 6,000 to 10,000 years ago that resulted

in a mutation in a gene called OCA2.

OCA2 is responsible for a protein called melanin

in our eyes.

That mutation occurred in Europe

and all blue eyed people today are distantly related

to that founder from 10,000 years ago.

But it’s not the only gene that’s important for eye color.

There’re about eight genes that we know about

that contribute to eye color in humans.

And even if you have the brown eyes version of OCA2,

sometimes you can end up with blue eyes.

And that’s due to the contributions

from those seven other genes.

@vandanlebron asks, How does 23andMe work?

Is it a scam?

Well, it’s not a scam.

In fact, 23andMe does a lot of basic genetics research

in addition to testing your DNA.

Here are two flow cells from an Illumina sequencer.

These can sequence hundreds of human genomes

in a single day.

We flow in the DNA, it binds to this glass slide,

and then the sequencer acts like a very powerful microscope

that can image the DNA.

But sequencing costs a lot.

It can cost about $1000 to sequence a whole human genome.

So how does 23andMe do it for only $100?

The secret is that they only sequence a small portion

of the genome, maybe 1/100 of 1%

of the 6 billion bases of the human genome.

And even those half-million bases can tell us a lot

about ancestry and specific traits you might have.

So they compare your genome to people

from Scotland or people from Brazil

and that’s how they can tell what percent

of you comes from here or what percent

of you comes from there.

@mothernaturegod asks, But why do genes mutate at all?

Genes can recombine in ways

that introduce genetic diversity.

Some mutations can give us stronger bones,

they can protect against heart disease,

or protect against severe COVID.

If this diversity didn’t happen at each generation,

we’d be like bananas.

Modern bananas are all clones of each other.

80 years ago, all bananas were a different clone,

the Gros Michel clone.

And then a fungal infection came

and wiped out the entire population.

Why? Because there was no genetic diversity.

So now let’s talk about the bad mutations.

The disease that comes to mind here is cancer.

Cancer arises from somatic mutations.

Those are the mutations you’re not born with

but that arise later in life.

They’re acting out of line and start growing

in ways that we don’t expect and don’t want.

@shittyquestions asks, How does sun affect your DNA?

Well, I have two words for you: wear sunscreen.

UV can be a very, very powerful mutagen for DNA

and what it does specifically, is these C-bases,

these green bases, it can turn them into T-bases,

these red bases.

Now, if this happens, most of these mutations,

they don’t do anything, it’s not very harmful.

But if it happens in certain genes that are important

in cancer, like oncogenes or tumor suppressor genes,

it can create deadly cancers like skin cancer.

That’s why you should wear sunscreen.

@mygulkae asks, God, why do my genes have

to make me five-one?

I’m so short.

Well, height is truly an amazing trait

because it’s super polygenic.

That means many, many different places

in the genome contribute to height.

We think that we can explain about 50%

of the contributions to height based on genes alone.

Well, what about the other 50%?

Well, that probably has something to do

with the environment you grew up in,

the foods you ate, things like that.

@eeelemons asks, Guys, quick, how are DNA

and genes related?

DNA is the letters that make up genes, A, T, C, and G.

When we arrange those letters in very specific ways,

we can write longer words and those words are the genes.

But they’re not just arranged randomly.

They’re actually arranged like chapters in a book,

each one on a different chromosome.

If chromosomes are like chapters in a book,

the human genome is the whole book,

everything that makes you, you.

@cosine_distance asks, Alexa am I related to Genghis Khan?

Maybe.

There are estimates that one in 200 men living today

carry a very similar Y chromosome,

which indicates a recent common ancestor.

All men inherit the Y chromosome

not from mom and dad, but just from their dads.

Moms don’t have a Y chromosome.

And Genghis Khan, he lived about 800 years ago.

So the math fits.

It’s possible that about 0.5% of the men living today

inherited their Y chromosome from a recent common ancestor,

maybe Genghis Khan.

@NinoClutch asks, Spider-Man is so raw.

Maybe we should try that DNA biotech cross gene splicing.

Well, I’m not sure we’re gonna see Spider-Man anytime soon,

but there is a lot of interest from biotech companies

and academic labs to understand spider silk,

which is five times stronger than steel.

Spider silk is very biocompatible,

very good for wound healing,

especially for wounds of the eye and the brain.

And there’s been many efforts to engineer spider silk

outside of spiders to make it in a recombinant way,

meaning not in spiders, but in other organisms,

like bacteria or plants.

Probably the best known example

of a recombinant protein is insulin.

This has helped millions of people

across the last four decades

since the first insulin was produced in bacteria.

@someonegoogled asks, How does CRISPR work, step by step?

Well, CRISPR’s not the thing in your fridge.

When we talk about CRISPR, especially in terms of medicine,

we’re normally talking about a protein called Cas9.

Cas9 comes from bacterial genomes, but we,

as genome engineers, have taken it and repurposed it

for uses in the lab and for genetic medicine.

The first step for CRISPR is to tell it

where to go in the genome.

And the way that we program the common CRISPR enzyme Cas9

is that we give it a little piece of RNA

that matches the DNA in the genome.

And so Cas9 can surf along the genes,

the DNA bases in the genome,

until it finds the perfect match for its guide RNA.

Once it finds that match,

then it knows where to make the cut.

And you can think of Cas9 like a pair of scissors.

It just snips at a specific location in the DNA.

Once it makes that cut, we can provide a template

to precisely repair the DNA

and correct a mutation for muscular dystrophy,

sickle cell anemia, or any of the other thousands

of inborn genetic diseases.

@DavidWi1939661 asks, A question from a layman.

As there are DNA strands in every one of our billions

of cells, how can editing one strand in vivo,

presumably in a single cell, extend to the DNA

in all other cells?

For a question from a layman,

I’m impressed with the use of in vivo.

There is so much DNA in our cells.

In just one cell, there’s about seven feet of DNA

if you took that balded up DNA in the nucleus

and stretched it out.

There’s about 30 trillion cells.

So if you multiply that out,

you get 40 billion miles of DNA.

That’s enough to go from the earth

to the sun a few hundred times.

So how does editing one cell impact other cells?

We normally wanna edit stem cells,

like blood stem cells or muscle stem cells,

and that’s because those cells

have the most potential to divide.

So when you edit the genome of those cells

it can replenish other cells, it can make other cells.

Once that edit is made, all the cells,

all the daughter cells, all the descendants

of that stem cell get the same edit in their DNA.

@simmelj asks, Could CRISPR technology be used

to fix all the people who don’t like cilantro?

It’s true, there are some people

that have a specific genetic variant

that causes cilantro to taste like soap.

Even if CRISPR could fix the people,

I don’t think this is the best use of the technology.

There are very serious diseases

where we already know CRISPR can make a huge difference.

These are diseases like sickle cell anemia

or beta thalassemia.

The people who suffer from these diseases,

there really aren’t great treatments for them.

But with CRISPR, we’ve already shown, work from our group

and many other groups, that we can reverse

on these diseases, even cure them,

by taking out blood cells from these patients,

editing them, and then putting them back.

So I think when we think as genome engineers

about what should we work on,

it’s really about these genetic diseases.

That’s where the initial focus of the field is gonna be.

@nillylol asks, How the F does DNA replication work?

Well, DNA replication is one

of the most beautiful things in biology.

So every time your gut regenerates

or a new layer of skin cells comes about,

those cells need a full copy of the human genome.

And every time you make a new cell, you make a new genome.

One way to visualize how this happens

is to take a double helix and see how the two halves

of the helix come apart right here in the middle.

When DNA replicates, the double helix comes apart

and each half helix has enough information

to make a whole new double helix.

The DNA polymerase, which is what makes new DNA, comes in

and sees these bases and can synthesize the pairs to them.

So T pairs with A and G pairs with C

and that way a whole new helix can be made

from just a half helix.

@CodyHeberden asks, Is alcoholism genetic?

Sometimes alcoholism runs in families,

but that doesn’t mean it’s genetic.

They’ve been genome-wide association studies

that have tried to figure out how much

of the contribution to alcoholism comes from our genes.

It seems to be somewhere between 40 and 60%.

There are also genetic variants that are associated

with the opposite of alcoholism.

So there’s some people of Asian descent that don’t tend

to drink, and that’s because when they do drink,

their face becomes flushed,

they become a little bit nauseous,

they don’t have the ability to metabolize the alcohol,

so it instantly makes them feel a little bit sick.

And in those folks with those variants,

there are very, very low rates of alcoholism.

They seem to be protected against the disease.

@PhonyHorse asks, How many times are scientists

gonna announce that they’ve ‘mapped the human genome’?

I feel like I see that same headline every few years.

Well, you’re not alone.

In reality, there’s been several different achievements

of genome mapping.

20 years ago on the White House lawn,

they announced the first draft human genome.

We knew for the first time how many genes there were

in the human genome, 20,000 genes.

But that genome had thousands of gaps.

It was only 90% complete.

A couple years later, they announced a more complete genome

where they only had about 400 gaps.

Last year, 2022, scientists had a truly gapless genome.

They called it Telomere-to-Telomere.

Telomeres are the ends of the chromosomes,

meaning that they had the complete sequence from one end

to the other end of the chromosome.

But we’re not done yet.

Now we need to sequence more genomes

from diverse populations because it’s not just

about getting the letters As, Ts, Cs, and Gs,

it’s about understanding really what they mean.

So I hate to break it to you,

but you’re gonna see this headline a few more times

over the next five, 10 years.

@lynnevallen writes, Does our DNA change?

The genome that we’re born with is more

or less the genome we have at the end of our lives.

But that doesn’t mean it doesn’t change.

Certainly we accumulate mutations over time.

But in addition to the primary sequence of DNA,

in addition to the As, Ts, Cs, and Gs,

there’s our epigenome.

The epigenome is kinda like Play-Doh on the genome.

It can control what parts of the genome

are more likely to be seen and which parts remain hidden.

And that epigenome is constantly changing.

It’s changing over time

and it changes over different organs.

So even though your genome is the same over time,

other things that are interacting with your genome

are changing quite a bit.

@ItsMackenzieM asks, Could CRISPR-Cas9 help those

who are highly susceptible to cancer reduce their risk,

like those who could possess

mutated tumor suppressor genes?

I don’t think CRISPR’s really being considered so much

for editing cancers themselves, but it’s certainly

being used to build better cancer therapies.

One thing that my lab works on

is using CRISPR to engineer immune cells.

Taking cells like T-cells from cancer patients

and training them, making them better fighters

of those cancers, making them less likely to give up

when they encounter the terrible environment of the tumor.

So we can take those blood cells, like T-cells,

out of a patient, we can edit them with CRISPR in the lab,

and put them back in the patient

and not only can we eliminate the cancer in some cases,

but we can install a security system that then

is with them for the rest of their life.

@NatHarooni asks, What if we could CRISPR people

to be a little more resistant to radiation,

less dependent on food and oxygen?

Sounds like it would benefit us on Mars.

I get this type of question a lot.

It assumes that we know a lot more

about human genetics than we actually do.

I think a much more serious

and important question is the ethical one.

Really, should we do this?

And the consensus in the field really

is that traits that are about enhancement, you know,

things that, you know, might be nice are really

probably not where the field of genome editing

should focus its efforts on.

Serious genetic diseases are really the current focus

of the field.

So those are all the questions for today.

Thanks for watching Genetic Support.

#Geneticist #Answers #Genetics #Questions #Twitter

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