2019 Schmidt Science Fellow Dr. Ina Anreiter discusses behavioural genetics research

U of T researcher recognized for her work modifying fruit fly foraging behaviours

2019 Schmidt Science Fellow Dr. Ina Anreiter discusses behavioural genetics research

Dr. Ina Anreiter from the University of Toronto was selected as a 2019 Schmidt Science Fellow for her research in behavioural genetics in April in New York.

The Schmidt Science Fellowship is a prestigious program that brings some of the best emerging scientists in the world together, and equips them with new skills to make a positive change in society. Candidates are chosen for their exceptional performance during PhD studies and strong intellectual curiosity to broaden the scope of their future research.

Each fellow, including Anreiter, will complete a year-long postdoctoral placement in a different field than their PhD topic to promote interdisciplinary thinking.

Anreiter’s work as a PhD candidate

Anreiter completed her PhD in the Department of Ecology & Evolutionary Biology at U of T, and was supervised by Dr. Marla Sokolowski. As part of her studies, Anreiter wanted to understand how genetics and environment could influence behaviours. She studied this by looking at the foraging gene of two strains of fruit flies with distinct foraging behaviours: the rovers and the sitters.

The rovers are more active and are usually willing to travel farther for food, while the sitters are less active and tend to travel shorter distances to forage.

“When the food is in the middle of the arena, you have a trade-off of safety versus getting to the food,” explained Anreiter in an interview with The Varsity. “So you can see this difference in rovers and sitters… It’s a circular arena, food is distributed in the middle, and you can see that sitters tend to hug the edges, while rovers are much more exploratory.”

An earlier paper published in 2017 by Anreiter and her colleagues described how they were able to genetically engineer the foraging gene to transform sitters into rovers.

Challenges along the way

Anreiter had to overcome multiple challenges to accomplish what she has. “The way that our publishing system works is very positive-result-oriented. It’s very hard to publish negative results, and there are many arguments to be made,” she remarked.

“We ended up publishing this really nice story about this one epigenetic regulator that regulates individual differences, but that wasn’t the only regulator that we looked at,” she continued. Epigenetic engineering makes modifications to an organism by altering which genes are expressed, rather than directly changing the DNA sequence itself.

However, her research team looked at many other regulators that did not show a positive result. “So there’s a lot of work that goes into this project that is never published because the results are not positive,” she elaborated.

She further acknowledged the challenges that she experienced as a PhD student, but she advised students to not get discouraged when a project seems to come to a dead end.

“It’s not the end of your PhD; it’s not the end of your research. You just change gears a little bit and continue with something new,” she concluded.

Next steps for future research

Anreiter’s work opens up many possibilities for future research in epigenetics. One of the significant findings in this study was that the effect of epigenetic regulators is dependent on the strain of fruit flies. In other words, “You have an interaction where the epigenetic modification is dependent on a genetic difference, and that’s an interaction which… when I started my PhD, [people] weren’t looking at,” she said.

“And that applies not only to fruit flies, not only to feeding behaviour, but applies broadly to animal research.”

Currently, Anreiter has undertaken a project in computer science, where she aims to develop a new computation mechanism to examine epigenetics modifications in RNA as a required component of the Schmidt Science Fellowship.

Offering advice to undergraduates about graduate studies, “Don’t do grad school because you are just not sure what you want to do, because grad school can be really, really tough,” she remarked. “But it is also really rewarding in my experience.”

“If you are excited about research, if you are excited about science, it is a really cool environment where you can really have the freedom of developing you own interests.”

How inflammation could link Parkinson’s, Crohn’s, and leprosy

U of T Dr. Shutinoski on high-impact genetics study

How inflammation could link Parkinson’s, Crohn’s, and leprosy

For years, the cause of the genetic link between Parkinson’s disease, Crohn’s disease, and leprosy has largely remained a mystery. However, a recent U of T-affiliated research effort has made significant strides by demonstrating that the cause seems to stem from inflammation.

Dr. Bojan Shutinoski, the first author of the study published in Science Translational Medicine at The Ottawa Hospital, explained to The Varsity that the gene in question, LRRK2, has been previously studied in relation to Parkinson’s and neuronal function. Shutinoski worked with co-authors, including Dr. Juliana Rocha of U of T, to complete the study.

Parkinson’s is caused in part by a lack of dopamine, which is produced by some neurons. This would suggest that the gene influences the neurons’ health. However, the study is the first to link a mutation in the gene to the immune system’s function.

The mutation in question is named ‘p.G2019s,’ and was linked by the study to an increased risk for developing Parkinson’s disease, Crohn’s disease, and leprosy. The risk stems from the mutation’s ability to cause the immune system to become hyperactive during periods of infection, which leads to high levels of inflammation.

The study’s design

Mice carrying the mutation, as well as ‘wild-type’ mice without the mutation, were infected with Salmonella typhimurium — a strain of bacteria that can cause sepsis.

Another experiment in the study infected mutated mice with a virus limited specifically to the peripheral system — the nervous system outside of the brain and spinal cord — and the mice were then compared with wild-type infected mice.

The analysis demonstrated that mice expressing the mutation were better able to control infection with higher levels of inflammation than the wild-type mice. However, this inflammation can be damaging.

The impact of inflammation on disease development

Inflammation specifically leads to an increased production of reactive oxygen species (ROS) in the brain, which can damage cell structures in high concentrations. These species damage or even destroy the neurons that produce dopamine, strengthening the link to Parkinson’s.

According to Shutinoski, one unique discovery from this experiment is that even in mice infected with the bacteria that did not infect the brain, inflammation still had an impact on the brain.

Another interesting finding of this study is that female mice with the mutation were found to have higher levels of inflammation than male mice. Similarly, in humans, Parkinson’s generally affects more men than women.

However, when Parkinson’s in humans is linked to p.G2019s, the opposite is true, and women have higher rates of the disease. This correlates with the findings in mice, yet the differences between the sexes are still open questions in science.

Applications of the study

Shutinoski suggested two clinical applications from this enhanced understanding of LRRK2. Primarily, since the LRRK2 gene produces an enzyme named dardarin, there are specific inhibitors that could hamper its activity.

However, more work must be done to ensure that the inhibitors are exclusive to the enzyme — otherwise, inhibiting other similar enzymes could harm the immune system response. Additionally, the regulation of ROS production could yield positive results in patients with increased inflammation, as a decrease in ROS could lead to healthier neurons and more regular dopamine production.

There is still much to learn about LRRK2, Parkinson’s, and inflammation, and this study has opened up a wide range of questions for researchers to tackle in the future.

One final aspect of this study is that it was a collaborative effort across several research groups. The main group working with LRRK2 worked with Crohn’s researchers in the local area.

To Shutinoski, the teamwork of the researchers was crucial to the study’s success.

“Science thrives in collaboration,” he said. “Our paper is… proof that collaboration works.”

Women in STEM: Kath Intson

PhD candidate discusses research, using Instagram to spread diversity in science

Women in STEM: Kath Intson

Kath Intson is a PhD candidate at U of T’s Department of Pharmacology and a popular science communicator on Instagram, with the handle @weekday_neuroscientist. Her neuroscience research could lead to a better understanding of various neuropsychiatric disorders.

Intson’s doctoral research centres on neuropsychiatric disorders

The malfunction of a receptor for a neurotransmitter named glutamate has been linked to the development of neurological disorders, such as schizophrenia, autism, and Alzheimer’s disease.

Intson studies the effects of altering the ability of the glutamate receptor in mice, under the supervision of Professor Amy Ramsey. She specifically studies the NMDA receptor.

To function properly, the receptor requires a protein subunit called gluN1 to function, which is produced from the expression of the GRIN1 gene. By performing a technique called ‘gene knockdown,’ Intson can suppress the gene’s expression.

This suppression enables her to examine the effect of a malfunctioning gene on mice. The results of Intson’s research could help advance knowledge of human health, due to the similarities between the anatomy, physiology, and genetics of mice and humans.

Intson’s secondary project examines how environmental factors can influence organisms to develop characteristics associated with schizophrenia.

Paired together, these projects could enable Intson to better our understanding of schizophrenia, as the disorder is a result of both genetics and environmental factors

Representation and science communication 

Intson developed her Instagram account in response to snarky messages online from users skeptical that Intson is a PhD candidate.

In a social media post online, Intson explained that it’s normal for scientists to have a life outside of their research. “It doesn’t matter what I look like on Instagram,” she said to The Varsity, summarizing her post. “I can still be a scientist.”

The post garnered attention, which encouraged Intson to post more science-related content on her account.

With her Instagram account, Intson strives to represent a “voice in the diversity that is STEM.” The ability to communicate with her followers on Instagram is essential for this.

“I think I just love chatting with people more than anything,” Intson said. “And if something that I post can spark a conversation, then that’s the whole goal of the account.” 

According to Intson, Instagram science communicators are pushing the idea that there is no ‘one image’ of a scientist — something that Intson strongly supports. 

“I think it’s true that literally every single person that I pass on the street could be a scientist,” said Intson. “I don’t conjure that one image.”

Representation to Intson means that leadership positions across professions are represented by people of races, genders, and orientations proportional to the diversity of individuals in these fields.

Role models and the experiences of women in STEM 

Intson credits her women mentors for giving her confidence and “arming [her] with the tools that [she] needed to go forth and conquer.”

Understanding the career trajectories, challenges faced, and work put in by her mentors has been especially valuable for Intson. 

“Just seeing somebody who’s in that position as a woman has been very helpful for me,” she said.

Women in STEM: Gabriela Krivdova

PhD student on challenges in scientific research, positive trends for women in science

Women in STEM: Gabriela Krivdova

Gabriela Krivdova, a graduate student from U of T’s Department of Molecular Genetics, studies blood stem cells under the supervision of Dr. John Dick. Her research may improve our understanding of leukemia, a human cancer that affects our blood and bone marrow.

“Failed experiments and rejected hypotheses”

Krivdova studies what makes blood stem cells different from mature blood cells, such as red and white blood cells. Her lab also aims to uncover the similarities and differences between healthy and cancerous blood cells by applying lab techniques used by geneticists.

While Krivdova remembers always liking the study of biology and chemistry, she recalled that her path to PhD candidacy was specifically sparked by her interest in immunology and genetics, which she developed during her undergraduate studies.

Her fascination with how the immune system works, as well as the complexity of the molecular mechanisms within our cells, led her to complete a Master’s degree at U of T under the supervision of Dr. Kathi Hudak.

Her research with Hudak was a rewarding experience that further solidified her interest in molecular biology research, and led Krivdova to her current position as a PhD student in Dick’s lab.

The biggest challenge that Krivdova faced stems from the regular prospect of failure associated with scientific research.

“I learned to not become discouraged from failed experiments or rejected hypotheses,” she noted. She added that unexpected findings are often learning opportunities.

The change in perspectives of women in science  

“I must say that I am very lucky to be in the lab I am in and work with so many amazing people,” Krivdova wrote. “I have not felt or experienced any challenges associated with my gender.”

While Krivdova has not personally experienced gender-related challenges in the workplace, she considers female scientist Rosalind Franklin to be her greatest inspiration.

“There are many [inspirations that I have],” wrote Krivdova, “but Rosalind Franklin comes to my mind as she did some pioneering work on the molecular structure of DNA and viruses during the time when scientific discoveries were dominated by men.”

Franklin was a chemist whose work in developing X-ray diffraction photographs was vital in the discovery of DNA’s structure. However, molecular biologists James Watson and Francis Crick saw Franklin’s photographs of X-ray diffraction without her knowledge.

These photographs proved crucial to their discovery of the double-helix structure of DNA, but neither scientist acknowledged Franklin’s work in their announcement published in Nature.

Watson and Crick both went on to receive the Nobel Prize in Physiology or Medicine in 1962 while Franklin remains officially uncredited.

Today, female scientists are more welcome in research. Krivdova noted how she’s been happy to see an increase in the number of female undergraduate and graduate students studying the sciences at U of T in recent years.

Krivdova has also seen a rise in gender and ethnic diversity in undergraduate laboratory classes which she instructs as a TA.

A piece of advice she would have given to herself as an undergraduate, she added, would be to focus on “the bigger picture in concepts,” and avoid dwelling on the little details of her coursework.

For women considering a career in scientific fields, Krivdova’s advice is to not give up and to continue pursuing their passions.

“Keep pursuing your interests,” she wrote. While there may be disappointments or failures along the way — whether it be from failed experiments or declined scholarships — her experience has shown that hard work pays off, and that there are always fascinating ideas to research as a scientist.

U of T student wins Pioneer Tournament with team for innovation that predicts human cancer risk

Hannah Le and teammates developed an innovation that blends AI, machine learning, and genomics

U of T student wins Pioneer Tournament with team for innovation that predicts human cancer risk

As many U of T students were wrapping up classes in March, first-year engineering student Hannah Le and her team won the third Pioneer Tournament — a worldwide competition that rewards participants for developing innovative ideas — for their project that used machine learning to identify and understand human biomarkers that predispose individuals to certain diseases.

Competition participants submit their project online and post weekly progress updates. The project then earns points awarded by contestants, who vote on the updates. After three weeks, the project becomes eligible to win a weekly prize, which is awarded to the team that wins the highest number of points at the end of that week. A project that places as a finalist for three weeks wins the team a larger award.

Le and her team members — Samarth Athreya, 16, and Ayaan Esmail, 14 — earned a top spot on the leaderboard in March and were awarded $7,000 from Pioneer to put toward their project. 

How the team got together

“Samarth, Ayaan and I met each other at an organization called The Knowledge Society in 2017,” wrote Le to The Varsity. The Knowledge Society is a startup incubator that exposes high school students to emerging technologies, such as artificial intelligence (AI), virtual reality, and brain-computer interfaces.

When the three innovators met, Esmail was working on a project that could accurately pinpoint and target cancer cells, while Athreya was working with machine learning models. With Le’s interest in genetics, the three decided to team up and investigate whether there was a way to use metabolic data to predict the onset of a disease.   

“I became incredibly curious on how we can decode the 3 billion letters [of DNA] in every cell of our body to increase human lifespan and healthspan,” wrote Le.

“Inspired by my grandmother who passed away due to cancer, I started asking myself the question: [could] there possibly be a way for us to predict the onset of cancer before it happens, instead of curing it?”

How Le’s team developed a model for predicting the risk of cancer development

At its core, the team’s AI platform uses a patient’s biological information to predict their risk of developing certain forms of cancer.

Metabolites are molecules that play a key role in maintaining cellular function, and some studies have shown that high levels of certain metabolites can signal the progression of lung cancer. But to develop and test their model, the team needed a large amount of metabolic data.

“To overcome such [a] limitation, we had the fortune to reach out to mentors such as the Head of Innovation at JLABS, [a Johnson & Johnson incubator], for further guidance and advice,” wrote Le. “As our team cultivates a stronger database, we would be able to produce more reliable results.”

“As teenagers we were far from experts [in] the field but we were really hungry to learn,” added Le.

As participants of the Pioneer Tournament, Le and her team received the opportunity to select a board of virtual advisors, who would provide guidance for their project.

“I recalled contacting Josh Tobin at OpenAI to ask him about the use of synthetic data in genomics research,” wrote Le. “[That enabled] us to understand both the strengths and weaknesses of such [an] approach, allowing us to pivot on what models to implement.”

The competition as a learning experience

Le remembers the Pioneer Tournament as an exciting chance to learn about different machine learning models and what made them effective as well as other projects that fellow participants were working on, all while attending courses at U of T.

“First year was an interesting journey of challenging course content, intertwined with unexpected personal growth,” wrote Le. “I learned how to strike a balance between working on personal projects, meeting interesting people, while completing my school work.”

And while Le is intrigued by the intersection of machine learning and genomics, she wrote, “I hope to keep an open mind and continue to be curious about the world around me.”

The genetics of risky behaviour

124 genetic variants associated with risk tolerance

The genetics of risky behaviour

According to a recent study published in Nature Genetics, risky behaviour may be linked to genetics. The international collaborative project involved 96 co-authors and identified 124 independent genetic mutations associated with general risk tolerance in humans. 

Risk tolerance refers to a person’s willingness to take a risk, with the goal of attaining a reward. “People who have higher risk tolerance are more likely to start up their own business, to invest in risky stocks, to do risky sports, take social risks and so on,” said Dr. Jonathan Beauchamp, one of the senior principal investigators and Assistant Professor of Economics at U of T, at the 2018 Paul G. Allen Frontier Group Conference. 

Risk tolerance “is such a fundamental parameter in the behavioural sciences,” continued Beauchamp. “It’s really at the core of all the economic models, macroeconomics, and also labour market decisions.”

The findings of this study provide examples of the many insights that can be gained from genome-wide association studies, which scan the genomes of many people in an attempt to associate genetic variants with particular outcomes. 

Genetic information and self-reported answers to questions regarding risk tolerance were collected from 12 different genetic databases, including UK Biobank and 23andMe. The study involved over one million people of European ancestry.

Once the researchers completed the data collection, genetic variants were matched with their respective risk tolerance profiles, and associations were made between various behaviours.

The 124 identified genetic variants play a small role in influencing risk tolerance when assessed individually. But together, the associations can help explain the genetic basis of risky behaviour. 

When the effects from all 124 variants were combined, a polygenic score, or numerical value that accounts for all variants in a single distinct genome, was created.

The polygenic score can explain up to about 1.6 per cent of variation in risk tolerance across a population. While this score does not have predictive value to determine the risk tolerance of a certain individual, it can be put to use in social science studies, which focus on the behaviour of a population.

The study also points to the high genetic association between risk preferences and risky behaviours. 

“There’s a debate in economics as to whether there is domain-general or domain-specific risk preferences, meaning whether your risk preference for health is correlated to your risk tolerance for driving fast or investing and so on,” said Beauchamp. “Some people have concluded that it seems they’re not correlated… but we find that, at the genetic level, there really seems to be a genetic component that affects risk preferences across domains.” 

The researchers found no support for the involvement of the main biochemical pathways previously thought to be related to risk tolerance, which included dopamine, serotonin, cortisol, estrogen, and testosterone. 

Instead, they found a role for the main excitatory and inhibitory neurotransmitters in genetically determined risk tolerance, glutamate and GABA respectively.

Beauchamp explained that this lack of corroboration is likely due to the relatively small sample sizes of previous studies. 

“To date… nearly all published studies attempting to discover the genetic variants associated with risk tolerance have been ‘candidate-gene studies’ conducted in relatively small samples ranging from a few hundred to a few thousand individuals.” 

As a result, the sample sizes from the candidate-gene studies were too small to identify genetic variants involved in risk-tolerance.

In part, this issue fostered Beauchamp’s support and involvement in the Social Science Genetic Association Consortium, which pools samples of genetic information so that researchers can look into genetic links using large sample sizes.

However, with all the media hype around genetics, Beauchamp warned not to neglect ‘nurture’ when it comes to human behaviour. 

“I think it’s important to emphasize that environment also matters, so we’re not saying that genes are the only thing important for risk,” said Beauchamp. 

U of T researchers uncover a network of genes linked to autism

The finding could explain the molecular basis of autism

U of T researchers uncover a network of genes linked to autism

Professor Ben Blencowe and his team at U of T have uncovered a network of around 200 genes that are linked to autism. Blencowe and his team published these findings in a study in Molecular Cell.

Autism spectrum disorder (ASD) comprises a range of conditions that affect social interaction, behaviour, and communication skills.

Because autism is not a single disorder but a spectrum of related conditions, there is no one discernible cause for it. Instead, a combination of biological, environmental, and genetic factors can be attributed to ASD.

There is also evidence of a strong genetic component in individuals with autism. Previous studies have found that in a family with one autistic child, the chance of having another autistic child is higher than the general population. Identical twins are also more likely to both develop autism than fraternal twins.

Most gene variations affect neural development and produce ASD symptoms through interactions with other genetic and environmental factors.

To determine a genetic link to autism, Blencowe and his team used a CRISPR-based method — a powerful gene editing tool — to identify neuronal microexons that are commonly misregulated in individuals with autism.

Microexons are small protein-coding regions in a gene locus, and are often involved in alternative splicing. Alternative splicing codes for different proteins in the same gene through different combinations of exons — protein-coding sequences — and removing different introns — non-coding sequences — from the messenger RNA (mRNA) transcript.

The altered versions of the mRNA transcript are then translated into several different types of proteins.

According to lead researcher Dr. Thomas Gonatopoulos-Pournatzis, the study was based on the team’s previous research which showed “that a network of neuron-specific microexons is frequently disrupted in the brains of autistic individuals.”

In other words, disruptions in alternative splicing affect how proteins communicate with one another, and could explain the molecular basis of autism.

The researchers isolated SRRM4, a protein that regulates splicing in neural cells, and found that mice with lowered SRRM4 expression displayed ASD-like traits.

The study reports that SRRM4 disruption in the brain has been found in one third of individuals with autism and has been identified as a convergent mechanism for the disorder.

“A critical challenge emerging from these findings is to identify the full repertoire of factors and pathways that converge on SRRM4 to control microexon splicing,” wrote Gonatopoulos-Pournatzis in an email to The Varsity.

In particular, SRRM4 is critical during embryonic development. It helps differentiate neural cells and promotes the development and proper functioning of a working adult nervous system.

In this study, the CRISPR-based screening identified and targeted specific DNA regions using a genome-wide approach.

“[It] systematically [inactivated] all protein-coding genes,” and tagged and isolated cells with altered microexon splicing levels. Then, high throughput sequencing identified “genes responsible for controlling micro-exon splicing,” wrote Gonatopoulos-Pournatzis.

“The screen performance exceeded our expectations and we captured over ~200 regulators that affect microexon splicing by direct or indirect mechanisms. Interestingly, these genes are enriched for genetic links to autism,” he added.

Uncovering “a core set of factors that are critical for microexon splicing” has implications beyond autism. Such factors could help inform researchers developing treatments for neurodevelopment disorders, including through the potential restoration of microexon splicing in misregulated cells.

In the future, the researchers hope to determine the association of microexon misregulation to specific behaviours characteristic to autism, and the roles of individual microexons.

Genes fads: research bias has neglected most of the human genome

Most genes remain a mystery nearly 15 years after scientists sequenced the human genome

Genes fads: research bias has neglected most of the human genome

When the human genome was first sequenced in 2003, scientists were optimistic that a medical revolution was on the horizon. The promise of personalized medicine seemed within reach. 

But 15 years later, this revolution hasn’t materialized and researchers are still uncovering the meaning of the genome. 

The research bias

Although the human genome has about 20,000 genes, researchers have focused most work on a small minority of genes. 

In 2011, Gary Bader, a professor at the Donnelly Centre for Cellular and Biomolecular Research, and his colleagues contributed to an article in Nature that highlighted this gap in research. 

More recently, a study led by Thomas Stoeger at Northwestern University reported that the gap remains and scientists are still studying only a fraction of the genome. 

Based on Stoeger’s work, approximately one quarter of genes have never been studied by a full publication and remain poorly characterized.

Gene trends through the decades 

Different genes have been popular over the decades, falling in and out of fashion with time. The National Library of Medicine (NLM) in the United States has been tracking publications on genes in its PubMed database, which revealed these trends. 

In the early 1980s, a significant chunk of genetic research focused on HBB, a gene critical for the development of hemoglobin, the molecule responsible for carrying oxygen in red blood cells.

Interest in hemoglobin was spurred by the work of researchers in the 1940s and 1950s who discovered the role of abnormal hemoglobin in sickle cell disease, a disorder in which individuals are at risk of developing multiple infections and pain episodes over their lifetime. 

But hemoglobin’s popularity was short-lived. The 1980s brought about new medical concerns that shifted genetic research to different diseases. 

In particular, an unknown immune system disease that was striking apparently healthy individuals at alarming rates and overwhelmingly affecting gay men shook the public and the medical community to its core. 

Scientists soon discovered that the mysterious illness was attributed to human immunodeficiency virus (HIV), a virus that targets CD4 cells, which are a type of mature T cell that help coordinate the immune response to an infection. 

The outbreak of HIV across the world garnered attention from politicians, policymakers, and the research community. By 1987, the CD4 gene dominated genetic research and retained its popularity until the mid-1990s. 

By 2000, the TP53 gene was gaining traction. Dubbed the ‘guardian of the genome’ by some, the TP53 gene is a tumour suppressor gene and mutates in nearly half of all human cancers. 

While completing his doctoral studies at the University of Vienna, Peter Kerpedjiev sifted through the NLM records and generated a list of the most studied genes. His work showed that TP53 is not the only popular cancer gene: four out of the top 10 most studied genes of all time — TP53, TNF, EGFR and ESR1 — all play some role in cancer development or are targets for cancer drugs.

TP53 was briefly dethroned by APOE, a gene that was initially associated with cholesterol but whose popularity exploded when researchers made a link between variants in the gene to a risk of Alzheimer’s disease. 

Kerpedjiev’s work showed that both genes remain popular in research today. 

Why are some genes more popular than others?

“Researchers usually first study these genes since they seem most important, and this is the answer why only a ‘minority’ have been studied so far,” wrote Stephen Scherer, director of U of T’s  McLaughlin Centre and The Centre for Applied Genomics at The Hospital for Sick Children, in an email to The Varsity. 

Steven Narod, Director of the Familial Breast Cancer Research Unit at Women’s College Hospital, whose research focuses on BRCA1 and BRCA2, two well-characterized genes, proposed that other factors could also be at play, such as the prevalence of mutations in the genes. 

He further explained that research tends to focus on genes “where the clinical implications are clear and the interpretation [of mutations] is straightforward.” 

There are also significant barriers that deter novice researchers from studying unknown genes, according to Bader. In an email, he explained that “it can be difficult for researchers to take risks and explore new territory because if they don’t succeed, they may not be able to continue being funded.” 

Based on Bader’s commentary, funding agencies are generally risk-averse and are less likely to support studies on lesser-known genes, which poses challenges to researchers interested in studying such genes. 

What does the future of genomics hold?

Scherer is hopeful that change will come over time. 

“[The genes] will all be studied but there are only so many resources (human and financial) available, and this will take some time,” wrote Scherer. 

Bader stressed that funding agencies can be part of the shift, by encouraging researchers to explore unknown regions of the human genome.  

For example, the US National Institutes of Health has established funding opportunities targeted at researchers investigating poorly characterized genes. 

The advances in genomic technologies will also likely play a role in the future. 

“New genomics technologies are accelerating progress and making it easier to discover interesting genes,” wrote Bader. He also encouraged researchers to “consider devoting a percentage of their time to exploring new territory, if they are not already doing this, in addition to the major projects that they work on.”

With advancing technologies and support from granting agencies, perhaps the rest of the human genome will become less of a mystery.