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.

The Screen Project slashes wait times for breast cancer screening

Women’s College Hospital initiative tests for BRCA1 and BRCA2 gene mutations

The Screen Project slashes wait times for breast cancer screening

Government-sponsored screening for breast and ovarian cancer in Canada can take up to a year to occur and can be denied based on a patient’s risk profile. To shorten wait times and offer universal testing, the Familial Breast Cancer Research Unit at Women’s College Hospital (WCH) has introduced The Screen Project initiative, which aims to make screening universally accessible to patients over 18 in Canada, and hopefully produce better patient outcomes.

The Screen Project has discounted its regular screening price to $99 USD for October, which is Breast Cancer Awareness Month. Ordinarily, the research unit screens patients for $165 USD. Results are expected within two to four weeks.

Why isn’t government-funded screening universal?

According to Dr. Steven Narod, Director of the Familial Breast Cancer Research Unit at WCH, screening through Canada’s universal healthcare system costs around $2,000–3,000 and wait times can last up to one year. As a result, as little as three per cent of women are eligible for the test per year.

But in 2017, the Familial Breast Cancer Research Unit found that commercial genetic testing could be completed in a shorter amount of time and for a fraction of the cost by sending samples to Veritas Genetics, an American genetic sequencing laboratory with whom the Unit has partnered for The Screen Project.

Veritas Genetics tests for BRCA1 and BRCA2, which are gene mutations associated with breast cancer. Women with a BRCA mutation have up to an 80 per cent lifetime risk of breast cancer and a 40 per cent lifetime risk of ovarian cancer versus a 12 per cent and a 1.3 per cent lifetime risk for women without the mutation, respectively.

How does the project work?

To provide a genetic sample for testing, patients order a genetic test kit from Veritas Genetics, provide a saliva sample, and then ship the kit and sample back to the Veritas Genetics lab. The lab tests the sample and releases the results to the patient and the Familial Breast Cancer Research Unit.

Patients with a negative test result receive an email or letter of notification. But patients who produce a positive test result receive an email or letter, as well as a personal phone call from a genetic counsellor at the Familial Breast Cancer Research Unit.

According to Narod, The Screen Project’s offer of “genetic testing for breast and genetic testing for ovarian cancer” for $165 USD is “ethical and wise,” since it is affordable for most Canadians.

However, Narod notes that the results of The Screen Project raise an ethical concern of whether it is “proper, right, and ethical to offer healthcare services outside of what’s insured by the public healthcare system.”

As The Screen Project continues, Narod plans to track the interest in genetic testing for breast and ovarian cancer in Canada, patient satisfaction afterward, and the actions that the project and patients choose to take to reduce their risk of breast and ovarian cancer following a positive test result.

Introducing Toronto’s first hospital-based refugee clinic

Large numbers of Syrian refugees are in need of healthcare, and U of T doctors are helping out

Introducing Toronto’s first hospital-based refugee clinic

Fifteen-thousand Syrian refugees are expected to arrive in Canada by the end of February; most of them are in need of general exams by family physicians, and U of T doctors are doing their part to help.

Meb Rashid is a professor in the Department of Family and Community Medicine (DFCM) at U of T and the director of the Crossroads Clinic at Women’s College Hospital, the first hospital-based refugee health clinic in Toronto. Due to the large numbers of Syrian refugees expected to enter Canada, Rashid created a program of rotating intake clinics comprised of family medicine health teams around Toronto to see refugees after they arrive in Canada for initial assessments.

Syrian refugees are checked twice for infectious diseases before coming to Canada, but chronic or latent diseases might go undetected, which is why seeing a family doctor is so important. Rashid’s network includes pediatricians, psychiatrists, dentists, and other specialists to provide quick and easy treatment for patients who need further care.

“I know from my own experience in Lebanon that Syrian refugees there have found it extremely difficult to receive adequate health care,” said Peter Goodspeed who is a journalist and volunteer at Lifeline Syria, an initiative to welcome and support 1,000 Syrian refugees as they settle in the GTA over the next two years through the help of sponsor groups. “So it is essential that they receive immediate attention on their arrival in Canada, simply to ease their own concerns and to speed and ease their integration into Canadian society,” explained Goodspeed.

Refugees may not seek out health care right away due to many different factors, such as difficulty in understanding Canada’s health care system. In late January and early February, Rashid’s network of clinics treated between 200 to 250 refugees in ten days. The network managed to see this many people, even though new refugees were not originally connecting with the clinics as quickly as they were arriving. The clinics were eventually able to reach such high success thanks to the help of Dr. Ben Langer and family medicine residents, who raised awareness of the clinics online and at meetings and fairs.

Some issues Syrian refugees are expected to face are uncompleted vaccinations, hypertension, diabetes, war-related injuries, and mental illness.

Concerns have been raised about a delay in psychological services for refugees suffering from post-traumatic stress or other psychological issues, but the refugee clinics around Toronto aim to offer friendly faces and a place to connect.

Many other U of T doctors are helping to connect Syrian refugees with health care as well. St. Michael’s Hospital doctors Ashna Bowry, professor at DFCM, and Gabrielle Inglis, U of T alumna, teamed up with Mike Evans, DFCM faculty member and YouTube creator, to create an Arabic-language whiteboard YouTube video. The video welcomes Syrian refugees to St. Michael’s Hospital and explains the procedures they will go through at the clinic. Evans said that the family medicine department wanted to create a welcoming experience for refugees.

“[W]hen you have more than enough, some people build fences… but some build a longer table,” said Evans. “We are in the table group.”

Thanks to the support of U of T doctors, the process of finding healthcare has gotten easier for Canada’s newest citizens.