Advanced math and computer science – and a healthy dose of collaboration – tackle genetics questions > News > USC Dornsife

Scientists in a new department at USC Dornsife discuss the mysteries within and moral issues surrounding our DNA.

In brief:

  • Faculties of the newly established Department of Quantitative and Computational Biology at USC Dornsife are exploring a variety of issues, from mapping missing sections of DNA to understanding the genetics shared by populations.
  • They also understand some moral questions surrounding genetics, such as whether to use DNA databases to locate criminals.

Inscribed in our cells could be our future, a story written before we were even born.

In every cell of the human body, a person’s genes contain instructions that affect traits such as height, eye color, and even whether or not we love the taste of coriander† And variations in our genes can change our risk of certain diseases, such as: breast cancer and schizophrenia

Of course it’s not that simple; many factors play a role. Some genes are only ‘activated’ under certain environmental conditions. Education or cultural forces can overcome genetic predisposition in many cases, although scientists aren’t sure to what extent.

Researchers at the new Department of Quantitative and Computational Biology (QBIO) at USC Dornsife College of Letters, Arts and Sciences are using advanced mathematics and computer science to answer some of the important questions about our genes, and the fate they predict.

The culture in QBIO emphasizes advanced computing and collaboration, aiming to create an ideal environment for discovery. At other universities, many of these scientists would be the sole computational researcher in their department. Here they are surrounded by them.

“If I run into a math problem in QBIO, I can just walk down the hall and talk to someone,” says Michael “Doc” Edgeassistant professor of Quantitative and computational biology. “This way I can really grow my work.”

Finding the missing link

Michael “Doc” Edge. (Photo: Courtesy of Michael Edge.)

In 2003, scientists sequenced most of the human genome for the first time, revealing all the code letters in our DNA. It took about a billion dollars and over a decade to complete. Since then, technological advancements have significantly reduced the effort. It would take just a few weeks and about $1,000 to do the same job today.

The technology that can currently produce a genome for this price does have drawbacks: about 3% of the human genome cannot be interpreted with this technology. Still, these missing sections may contain genetic variations that can tell us a lot about ourselves.

“If we want to predict how someone’s genome will affect how they respond to a drug, or how likely they are to develop a particular disease, if we’re missing a fraction of it because we’re using this shorter-readable technology, then we see not the full picture”, says Mark Chaissonassistant professor of quantitative and computational biology.

chaisson’s lab develops powerful, intricate methods to add back that missing percentage. Once the gap is filled, Chaisson and his students will be able to learn more about genetic variation and how it may contribute to hereditary diseases.

Much of his work has focused on structural variants, which occur over a large portion of the DNA sequence rather than just a single, small point.

Much of his work uses large-scale studies and massive databases, meaning the powerful computers at QBIO are vital to his research – as are his colleagues.

“Everything we produce is either the result of a person sitting in front of the computer themselves, or talking to someone else here and learning a new skill or sharing ideas,” Chaisson says.

Complex genetics

Mark Chaisson. (Photo: Courtesy of Mark Chaisson.)

About in Edge’s labhe and his students conduct research into ‘complex traits’, traits that arise from a combination of genetic variation as well as behavioral factors and environmental conditions.

For example, a person’s height is influenced by hundreds of genetic variants, and it’s how those variants coalesce that determines how tall a person gets. However, height is also strongly influenced by diet. A person with genetics who could normally push six feet may become shorter due to insufficient nutrition.

Edge also studies issues of genetics and privacy. A recent proliferation of consumer genetic tests at home, used to research a person’s ancestry or predisposition to certain diseases, has led to massive databases of genetic information

Law enforcement officers and consultants are also increasingly searching a subset of these databases using DNA taken from crime scenes, a method called “forensic genetic genealogy.” The Golden State Killer from California, who killed at least 13 people and was hunted since the 1970s, was finally identified in 2018 thanks to these kind of searches

Edge has written about the power of this type of detective work as well as the privacy concerns it raises. Someone who uploads their personal genetic test to an ancestor database is unknowingly uploading information about all of their relatives who share their genes.

“When you upload a test, it doesn’t just affect you; it may affect some people you’re related to, many of whom you’ve never met,” Edge says. The rules around these searches are currently only enforced by the individual companies. Only two states have forensic genealogy laws.

“The majority of people I’ve talked to don’t want to ban searches. They just want to think through all the implications before allowing unfettered access.”

find family

Despite genetics’ incredible potential to inform us about diseases and human history, it also has a somewhat uneasy origin story.

Since its inception in the early 20th century, genetics has often been intertwined with eugenics, the attempt to breed perceived flaws out of the human race. Genetic research was often pursued or co-opted by eugenicists eager to eliminate ‘undesirable’ hereditary traits through sterilization or anti-mixing laws.

Jazlyn Mooney. (Photo: Courtesy of Mooney.)

“The controversy in genetics stems from racism that was introduced to our field quite early. The early motivation for doing genetic studies was to show that there are differences between presumed races that make some groups superior to others,” he says. Jazlyn Mooney, Gabilan Assistant Professor of Quantitative and Computational Biology. “Now our goal is to push our work in the right direction while recognizing that this complex history still exists.”

Mooney is a new addition to USC Dornsife, after its founding her lab in the spring of 2022. She focuses on population genetics – the genetics shared within a particular group of people, how traits are passed on and expressed, and how diseases can be inherited.

She is one of many new geneticists looking to lift the field from the shadows of the past. Data sets used in genetic research and stored in ancestry databases are primarily European, with little representation of non-Europeans such as African, African American, or Indigenous groups.

Mooney is particularly interested in understanding the history and diversity of non-European and mixed populations. Mixed populations, such as African Americans, occur when people have genetic ancestry from two or more different sources, such as Europe and Africa.

This work is personal to Mooney, whose father is African American and mother Hispanic and Native American. She can trace her mother’s side of the family back to Spain as far back as the 16th century, but has little information about her father.

“We want to do good things for human health, but if you don’t have non-European people in your data, those people are at a disadvantage,” Mooney says.

“That’s the most important thing when we think about the future of human genetics. How do we integrate diverse groups into our data sets and also ensure that their community sees a tangible result of the science?”

For a scientist like Mooney, who is just starting her career, the QBIO department is an excellent place to grow. “We have a lot of young faculty members, which is different from a lot of other genetics departments,” Mooney says. “As head of department, Remo Rohs really has a vision for the younger faculty members. It’s a great place to be.”

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