How Geneticists Link Genes to Diseases

Question: During your work on the human genome, you linked many genes to specific diseases. How are these links established?

Francis Collins:  It’s too bad you can’t actually see DNA easily under a microscope and scan across a double helix and read out the sequence of bases that amounts to the information content because it would be easier, I think, to explain then how a geneticist goes about tracking down the molecular basis of a disease at the molecular level.  Our methods are indirect—they’re very powerful, they’re really highly accurate, but they’re not as visual as you might like.  We do have methods though, now, that allow you to read out with high accuracy, all three billion of the letters of the DNA instruction book, those letters are actually these chemical bases.  The chemical language of a DNA is a simple one, there’s only four letters in the alphabet.  Those bases that we abbreviate A, C, G and T.  and we have methods of being able to compare then the DNA sequence of people who have a disease versus people who don’t and look for the critical differences in order to nail down something that might be the cause.  

Well since, however, we all differ in our DNA sequence by about a half of one percent, you wouldn’t get very far if you basically sequenced my DNA and the DNA of somebody with Parkinson’s Disease trying to figure out what the differences were because it would be way too many of them. But if you’re willing to do that for a large number of people, you kind of average out all the noise and the difference that matters begins to be more and more clear.  That’s an overly simplified description of how a geneticists goes about zeroing in on the actual molecular cause of a complex or a simple disease.  This works most readily for diseases that are highly heritable; cystic fibrosis, Huntington’s Disease—those are conditions where as single mutation very reproducibly results in the disease.  

It’s been a lot tougher for diseases where the inheritance is muddy.  If you take diabetes, for instance, which is what my lab primarily works on, or you take asthma or high blood pressure, that is not a set of conditions where one gene is involved in risk, there are dozens of genes involved in that and no single one of them contributes very much, but you put it all together and the consequence to that individual may tip them over the threshold into having the illness.  We’re in the throes right now trying to sort that part out for the common diseases that we know have hereditary influences because they run in families but they’re much more complicated than say, cystic fibrosis.

Question:
Was there anything that totally surprised you in your research on the genome?

Francis Collins: There were a lot of surprises a lot of times where you just marveled as what you had uncovered and felt like you must have really somehow missed it when you were making guesses about what would be there.  I guess the one that startled most us the most profoundly was how few protein coding genes there actually are in the genome.  The old paradigm about DNA-makes-RNA-makes-protein, well then a stretch of DNA is going to make a protein, how many genes does it take to specify a human being?  Hooh, you would think there would be an exorbitant number.  And various estimates have been put forward before we knew the answer that we’re in the neighborhood of 100,000 to 150,000. Ultimately, it turns out we only have about 20,000 protein coding genes.  A breathtakingly short list of instructions for an organism as complex as homo sapiens.  

There are other genes that don’t code for protein that are turning out to be pretty important, so in a certain way we’re rescuing our sense of complexity by discovering there are other categories or genes that don’t have to be of the protein coding sort, but it is still astounding to think that just 20,000 of these protein coding genes is enough to take a single cell, which we all once were and inspire this program of elaborate complex development into a human being, including a nervous which is beyond our ability at the present time to even quite contemplate because of its complexity.

Recorded September 13, 2010
Interviewed by David Hirschman

The former director of the National Human Genome Research Institute describes how researchers compare DNA sequences to pinpoint which genes cause which diseases.

China's "artificial sun" sets new record for fusion power

China has reached a new record for nuclear fusion at 120 million degrees Celsius.

Credit: STR via Getty Images
Technology & Innovation

This article was originally published on our sister site, Freethink.

China wants to build a mini-star on Earth and house it in a reactor. Many teams across the globe have this same bold goal --- which would create unlimited clean energy via nuclear fusion.

But according to Chinese state media, New Atlas reports, the team at the Experimental Advanced Superconducting Tokamak (EAST) has set a new world record: temperatures of 120 million degrees Celsius for 101 seconds.

Yeah, that's hot. So what? Nuclear fusion reactions require an insane amount of heat and pressure --- a temperature environment similar to the sun, which is approximately 150 million degrees C.

If scientists can essentially build a sun on Earth, they can create endless energy by mimicking how the sun does it.

If scientists can essentially build a sun on Earth, they can create endless energy by mimicking how the sun does it. In nuclear fusion, the extreme heat and pressure create a plasma. Then, within that plasma, two or more hydrogen nuclei crash together, merge into a heavier atom, and release a ton of energy in the process.

Nuclear fusion milestones: The team at EAST built a giant metal torus (similar in shape to a giant donut) with a series of magnetic coils. The coils hold hot plasma where the reactions occur. They've reached many milestones along the way.

According to New Atlas, in 2016, the scientists at EAST could heat hydrogen plasma to roughly 50 million degrees C for 102 seconds. Two years later, they reached 100 million degrees for 10 seconds.

The temperatures are impressive, but the short reaction times, and lack of pressure are another obstacle. Fusion is simple for the sun, because stars are massive and gravity provides even pressure all over the surface. The pressure squeezes hydrogen gas in the sun's core so immensely that several nuclei combine to form one atom, releasing energy.

But on Earth, we have to supply all of the pressure to keep the reaction going, and it has to be perfectly even. It's hard to do this for any length of time, and it uses a ton of energy. So the reactions usually fizzle out in minutes or seconds.

Still, the latest record of 120 million degrees and 101 seconds is one more step toward sustaining longer and hotter reactions.

Why does this matter? No one denies that humankind needs a clean, unlimited source of energy.

We all recognize that oil and gas are limited resources. But even wind and solar power --- renewable energies --- are fundamentally limited. They are dependent upon a breezy day or a cloudless sky, which we can't always count on.

Nuclear fusion is clean, safe, and environmentally sustainable --- its fuel is a nearly limitless resource since it is simply hydrogen (which can be easily made from water).

With each new milestone, we are creeping closer and closer to a breakthrough for unlimited, clean energy.

The science of sex, love, attraction, and obsession

The symbol for love is the heart, but the brain may be more accurate.

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Golden blood: The rarest blood in the world

We explore the history of blood types and how they are classified to find out what makes the Rh-null type important to science and dangerous for those who live with it.

Abid Katib/Getty Images
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A new study suggests that reports of the impending infertility of the human male are greatly exaggerated.

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