Fri. Feb 26th, 2021

Hard to overdo The importance of bargain-basement pricing of the human genome. The cost of understanding a person’s genetic code dropped from $ 10 million to $ 1,000 or less over a decade. This means that think of a person’s genome as a single work of literature, which encapsulates a life from childhood to old age, with all the unique strengths and weaknesses that characterize a human. For a genetics researcher, a single genome can make for fascinating reading, but the story it tells is limited. A library containing one million genomes will allow researchers to compare the complexities of a million lives, possibly leading to precisely targeted therapies for specific diseases and for individual patients.

President Barack Obama’s $ 215 million Precision medicine initiativeAnnounced in January, this research intends to accelerate. Funding is modest, but the objective is ambitious: to build a research team of one million volunteers ready to share genetic and other medical information in a new era of accurate diagnosis and treatment. Running this change is high-throughput sequencing, a relatively new advance that enables researchers to understand mountains of genetic information quickly and at low cost. Gene panels simultaneously use high-throughput sequencing to assess millions of genetic mutations.

Dr. Elizabeth McNally, director of the Northwestern University Center for Genetic Medicine, Who spoke on October 19 At the US News Hospital of Tomorrow Conference, a precision medicine pioneer involved in this research. The Northwestern NUgene project is also home to Biobank, a repository of DNA of 12,000 volunteers and one of 10 partner institutions with an early lead in the field. McNally, a cardiologist, spoke to US News about the promise and challenges. (The interview has been edited for length and clarity.)

Can you give us a status report on exact medicine?

I have been running a cardiovascular genetics clinic for many years, focusing on heart disease that runs in families. When we started, we had no genetic testing. Did revolutionization actually bring genetics into practice, with some technological developments taking place in 2006 or 2007, including [high-throughput] Indexing. Now we see the fruit [technology] Is making its way into practice. Gene panels are coming out, and all this has to be tested. Secondly, we now have large databases of human genetic sequences that begin to understand how much [genetic] Vary from person to person. It surprises many people how much there really is. The challenge before us is to understand all these changes [figure out how to use it] To understand the health consequences and how we manage people with drugs.

To what extent has this information simplified or complicated things?

Dr. Elizabeth McNally is director of the Center for Genetic Medicine at Northwestern University and a professor in the departments of Medicine and Biochemistry, Molecular Biology and Genetics.Courtesy Northwestern University

There are more rare variations than people actually think. When I say rare, I am talking about their presence in every 1 out of 100 people, 1 out of 200 people, 1 out of 2,500 people. This means that there is an 85 percent variation in the genome of anyone, but it is unique to them and their families. The combination of these variations is truly unique. Only 15 percent of the variation is common, which means that it is found at a higher frequency in the population.

Can you explain it in simple words?

When you look at a room of people, we all are amazingly different from each other. We are much different than we imagine. Each of us has unique differences. When you try to do yoga across the population, it is difficult to do so. At the same time, it is very useful for managing individual patients. We have a lot of great information that is helping individuals and their families. It’s funny; When I give these talks, they say, ‘You are trying to help people’. This is the exact medicine.

What are its implications for research linking genetic mutations to disease?

The trouble is that all genome-wide association studies are built on the same basis [diseases are caused by] Common Variation. This is why these studies have not far outweighed us in using that information to manage individual patients. They are looking at such a small part of the genome, and it is no different among populations.

Are these rare variants likely to disturb gene sequences that have a major impact on human disease?

This is my bias. I agree that we are not in the majority view from that point of view. What I do is order genetic testing on individuals who have forms of heart failure. If I order a test of 100 different genes, then we [may] Is rare [genetic variants] We think that is associated with that person’s illness. Now, across [a big] The resulting population does not matter much.

Almost I told you about heart failure that we will also say about breast cancer, some other types of cancer and neurological diseases. This is indeed meaningful to individuals, but difficult to conclude in a population.

Can you talk about genetic profiling and how it is used to estimate risk, diagnose disease, and implement drug treatments?

Again, there is a high expectation that the 15 percent variance that is normal determines a lot, which person suffers from high blood pressure, and how a person responds to medications. But it turns out that [not the case]. If you have decided to use [a genetic testing service that predicts your risk of getting common diseases, it might] Let us know that you have a 1.4 times higher risk of macular degeneration or something along those lines, but the overall risk is relatively low. They cannot tell you that you have a great risk of something, because the stuff they test is very common in the population. [The variants may be there, but they’re not always associated with disease.] Once you start seeing rare changes … they are incredibly powerful within gene families.

Therefore, if you are a woman and you take BRCA mutations – and we know that less than 10 percent of breast cancer is caused by BRCA mutations – your risk is actually very high in your lifetime of getting breast cancer. It is a rare gene, but the risk associated with it is actually very high.

If you know that you have a high genetic risk of inherited disease, how do you act on the information?

What we are talking about, we are thinking a little about how a person’s future can be. And again, it’s a risk assessment – when you do a genome on someone you’re doing a risk assessment. And, yes, we can reduce the risk for many types of disorders. Heart disease – we can reduce the risk. If it’s really bad [heart] Rhythm, we can put in [a pacemaker or defibrillator], We can put people on drugs and thus save lives. For cancer, we look at things like improving surveillance. Someone who performs BRCA mutations usually undergo mammograms at an earlier age, or, as In case of Angelina Jolie, If she is really worried, then remove her breasts. If you are in a family with colon cancer, and you are at greater risk, you will not wait until you are 50 years old to have your first colonoscopy.

How close we are to real precision medicine: A personal diagnosis kept with a personalized treatment plan?

We are already seeing a lot of successes. If you have a tumor these days, it is actually quite likely that the tumor will be profiled in some way so that … a chemotherapy plan for that tumor will be put together. We now have genes that can be used to determine how certain drugs are given, such as whether or not you should dilute on aspirin. As things are evolving and getting into regular practice. And, again, we’re definitely [using] This is for many inherited diseases. Genetic mutations and inheritance play a huge role in many of the diseases we feel. We can consult family members and give them good advice. We see that in every branch of medicine.

Can you cite diseases where it is becoming common?

Almost any type of cancer… in part because we know that cancer is a genetic disease to a large extent. Lung cancer is a great example of this. There are some very obvious gene mutations that will change the recommendation of how you treat and what medications you are given. Some types of head and neck cancer, exactly the same thing, where you will see certain types of markers and you will completely change the recommendation of how the person is treated, whether they are going to upfront chemotherapy or surgery Are. They are two very different courses of action. Almost every type of leukemia and lymphoma is now [tested] For genetic system; We have very different treatments for them. Now we consider them a different disease from each other.

Does this mean that we are beginning to think again about how we classify these diseases?

What we used to consider as a group of many diseases, we are now understanding various diseases compiled together in many cases. In my region, heart, we are starting to see this happen. We considered all forms of heart failure to be one. We are starting to see, no, there are subtypes of heart failure that depend on which gene mutations you have. In this group, should we think [implanting a pacemaker and/or defibrillator] Soon because they are more prone to arrhythmia? There are indeed clear areas in neurology where it is also emerging. Epilepsy is a great example. We have all these different medicines to treat epilepsy and now it is a random guess as to which drug will be applied to each patient. When we understand the genetics of epilepsy better, we will be able to make more rational choices.

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