With 100% of the human genome mapped, new genetic diagnostic and disease screening tests may soon be available for clinical laboratories and pathology groups
Utilizing technology developed by two different biotechnology/genetic sequencing companies, an international consortium of genetic scientists claim to have sequenced 100% of the entire human genome, “including the missing parts,” STAT reported. This will give clinical laboratories access to the complete 3.055 billion base pair (bp) sequence of the human genome.
If validated, this achievement could greatly impact future genetic research and genetic diagnostics development. That also will be true for precision medicine and disease-screening testing.
Completing the First “End-to-End” Genetic Sequencing
In June of 2000, the Human Genome Project (HGP) announced it had successfully created the first “working draft” of the human genome. But according to the National Human Genome Research Institute (NHGRI), the draft did not include 100% of the human genome. It “consists of overlapping fragments covering 97% of the human genome, of which sequence has already been assembled for approximately 85% of the genome,” an NHGRI press release noted.
“The original genome papers were carefully worded because they did not sequence every DNA molecule from one end to the other,” Ewan Birney, PhD, Deputy Director General of the European Molecular Biology Laboratory (EMBL) and Director of EMBL’s European Bioinformatics Institute (EMBL-EBI), told STAT. “What this group has done is show that they can do it end-to-end. That’s important for future research because it shows what is possible,” he added.
In their published paper, the T2T scientists wrote, “Addressing this remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium has finished the first truly complete 3.055 billion base pair (bp) sequence of a human genome, representing the largest improvement to the human reference genome since its initial release.”
Tale of Two Genetic Sequencing Technologies
Humans have a total of 46 chromosomes in 23 pairs that represent tens of thousands of individual genes. Each individual gene consists of numbers of base pairs and there are billions of these base pairs within the human genome. In 2000, scientists estimated that humans have only 30,000 to 35,000 genes, but that number has since been reduced to just above 20,000 genes.
According to STAT, “The work was possible because the Oxford Nanopore and PacBio technologies do not cut the DNA up into tiny puzzle pieces.”
PacBio used HiFi sequencing, which is only a few years old and provides the benefits of both short and long reads. STAT noted that PacBio’s technology “uses lasers to examine the same sequence of DNA again and again, creating a readout that can be highly accurate.” According to the company’s website, “HiFi reads are produced by calling consensus from subreads generated by multiple passes of the enzyme around a circularized template. This results in a HiFi read that is both long and accurate.”
Oxford Nanopore uses electrical current in its sequencing devices. In this technology, strands of base pairs are pressed through a microscopic nanopore one molecule at a time. Those molecules are then zapped with electrical currents to enable scientists to determine what type of molecule they are and, in turn, identify the full strand.
The T2T Consortium acknowledge in their paper that they had trouble with approximately 0.3% of the genome, but that, though there may be a few errors, there are no gaps.
“You’re just trying to dig into this final unknown of the human genome,” Karen Miga (above), Assistant Professor in the Biomolecular Engineering Department at the University of California, Santa Cruz (UCSC), Associate Director at the UCSC Genomics Institute, and lead author of the T2T Consortium study, told STAT. “It’s just never been done before and the reason it hasn’t been done before is because it’s hard.” (Photo copyright: University of California, Santa Cruz.)
Might New Precision Medicine Therapies Come from T2T Consortium’s Research?
The researchers claim in their paper that the number of known base pairs has grown from 2.92 billion to 3.05 billion and that the number of known genes has increased by 0.4%. Through their research, they also discovered 115 new genes that code for proteins.
The T2T Consortium scientists also noted that the genome they sequenced for their research did not come from a person but rather from a hydatidiform mole, a rare growth that occasionally forms on the inside of a women’s uterus. The hydatidiform occurs when a sperm fertilizes an egg that has no nucleus. As a result, the cells examined for the T2T study contained only 23 chromosomes instead of the full 46 found in most humans.
Although the T2T Consortium’s work is a huge leap forward in the study of the human genome, more research is needed. The consortium plans to publish its findings in a peer-reviewed medical journal. In addition, both PacBio and Oxford Nanopore plan to develop a way to sequence the entire 46 chromosome human genome in the future.
The future of genetic research and gene sequencing is to create technologies that will allow researchers to identify single nucleotide polymorphisms (SNPs) that contain longer strings of DNA. Because these SNPs in the human genome correlate with medical conditions and response to specific genetic therapies, advancing knowledge of the genome can ultimately provide beneficial insights that may lead to new genetic tests for medical diagnoses and help medical professionals determine the best, personalized therapies for individual patients.
Best Practices for Launching Profitable, Efficient NGS Tests for Hereditary Risk FREE LIVE WEBINAR WITH Q&A Held Wednesday, June 23, 2021 | 1-2 pm EDT Sponsored By STREAM ON-DEMAND NOW Next-generation sequencing (NGS) is gaining momentum, but implementing it well has its challenges The decreasing cost of implementing NGS has many clinical laboratories considering expanding the scope and complexity of their hereditary testing services to include NGS. However, this expansion comes with a...
As consumer demand increases for medical laboratory testing services that bypass the supervision of primary care doctors, clinical laboratories may be affected
Direct-to-consumer (DTC) genetic testing organizations and telecommunications companies in South Korea are collaborating to help consumers stay informed of their health status by sending lab test results directly to their mobile devices without requiring physician involvement. What can labs in the West learn from these developments?
Founded in 2015, NGeneBio provides smartphone-based healthcare services for individuals who solicit genetic testing. Through the partnership, KT plans to combine its knowledge of artificial intelligence (AI) and cloud computing with NGeneBio’s genetic decoding expertise to “provide services such as tailored health management (diet and exercise therapy) services, and storage and management of personal genome analysis information.”
No Doctors Involved?
Outside of genealogy, the general intent of DTC genetic testing is to equip consumers with certain genetic data that may help them manage their healthcare without requiring visits to their healthcare provider. The healthcare information provided through the NGeneBio venture will include data delivered directly to customers’ smartphones on the status of their:
skin,
hair,
nutrition, and
muscular strength.
According to an article in Korean business news publication Pulse, “Genetic test services in Korea are restricted to some 70 categories, such as the analysis of the risk of hair loss, high blood pressure, and obesity.”
Last September, Pulse reported, Korean mobile carrier SK Telecom Co. announced a similar partnership with Macrogen Inc. to introduce a mobile app-based DNA testing service called “Care8 DNA.” To utilize this service, consumers order a DNA test kit, take a saliva sample via mouth swab, and then send the kit to a clinical laboratory for analysis. Users typically receive their test results on the Care8 DNA app (available from both Google Play and Apple’s App Store) within a few weeks.
The service costs ₩8,250 South Korean won ($7.36 US) per month. A one-year subscription to the service costs ₩99,000 won or $88.36 US. The Care8 DNA app features 29 testing services, including:
skin aging,
possibility of hair loss,
resistance to nicotine,
the body’s recovery speed after exercise,
and more.
Along with those results, consumers can receive personalized health coaching guidance from professionals like nutritionists and exercise physiologists to improve their overall wellbeing, Pulse noted.
KoreaTechToday reports that the Macrogen/SK Telcom Care8 DNA app (above) “links the consumer immediately to a gene testing company instead of going through a medical institute first. BIS Research [a marketing research and intelligence company located in Freemont, Calif.] estimates the global direct-to-consumer (DTC) gene test market would increase to ₩7.6 trillion won in 2028.” That is more than $6.7 billion US dollars. Such a shift toward DTC home testing would likely have a huge financial impact on clinical laboratories that process genetic tests as well as the healthcare providers who order them. (Photo copyright: SK Telecom Co.)
In February 2019, Macrogen became the first company in South Korea to take advantage of the government’s relaxed regulations on DTC genetic testing, Korea Biomedical Review reported. In addition to the basic services offered through the Care8 DNA app, Macrogen’s DTC tests also can cover 13 diseases, including:
Other Korean Genetic Testing Companies Adding DTC Services
“Industry officials think DTC genetic tests should include testing for diseases,” an industry official told Korea Biomedical Review in April. “There will be more companies who make these attempts.”
“A DTC genetic test is a contactless healthcare service suitable for the COVID-19 era. The expansion of detailed test items allows users to comprehensively check nutrients, obesity, skin, hair, eating habits, and exercise characteristics at one time,” an official at Theragen Bio told Korea Biomedical Review. “We expect that our service will attract more attention from consumers.”
What Can Be Learned?
Countries in Asia—particularly South Korea, Japan, and Taiwan—are among the fastest adopters of new technology in the world. Thus, it can be instructive to see how their consumers use healthcare differently than in the West, and how those users embrace new technologies to help them manage their health.
It is not certain how all this will impact clinical laboratories and genetic doctors in the western nations. Direct-to-consumer genetic testing has had its ups and downs, as Dark Daily reported in multiple e-briefings.
Nevertheless, these developments are worth watching. Worldwide consumer demand for genetic home testing, price transparency, and easy access to test results on mobile devices is increasing rapidly.
Medical technologists and clinical laboratory professionals are the unsung heroes of the COVID-19 pandemic and the public is beginning to notice
Medical technologists (MTs) and clinical laboratory scientists (CLSs) are the foundation of every successful clinical laboratory. But they seldom make the news. Therefore, it is worth noting, during this COVID-19 pandemic, when clinical laboratory professionals receive public recognition for the important role they play in fighting the disease.
A news story published by the Canadian Broadcasting Corporation (CBC), titled, “Lab Tech Who Found B.C.’s 1st Case of COVID-19 Recalls ‘Sheer Terror’ of Discovery,” describes a laboratory technologist’s experience in British Columbia when she discovered the Canadian province’s first positive case of COVID-19 in January of 2020.
Finding COVID-19 for the First Time
On January 27, 2020, Rebecca Hickman, Public Health Laboratory Technologist, Molecular Biology and Genomics at BC Centre for Disease Control (BCCDC) was carefully monitoring samples for COVID-19 and fearing a positive result for the SARS-CoV-2 coronavirus when her worst fear appeared before her eyes.
“I actually started to see it get positive within a few seconds,” Hickman recalled. “My first feeling was sheer terror, from a personal point of view.”
When Hickman realized a sample was going to test positive, she called Tracy Lee, Technical Coordinator at BC Centre for Disease Control and co-designer of the BCCDC’s COVID-19 test. Hickman had to interrupt Lee in a meeting, who then hurried to the lab to watch the test complete. It was a definite positive, the first confirmed case in British Columbia.
“To design, validate, and implement a molecular laboratory test usually takes months if not years, and so to do that in the span of days is a huge achievement,” Hickman told the CBC.
The following day, it was announced to the residents of BC that the COVID-19 coronavirus was in their province and that they needed to start taking necessary precautions. “This is the first time in my life I’ve ever found things out before I read it in the news,” Hickman said.
Supply Shortages Challenge British Columbia Clinical Laboratories
Hickman noted there have been several challenges in dealing with COVID-19 over the past year. “The instability and craziness of it all has been the hardest part,” she said. Last spring, the BC lab, like most labs, had to deal with a shortage of supplies and personal protective equipment.
According to BC Centre for Disease Control (BCCDC) data, as of March 2, 2021, there have been 81,367 confirmed cases of COVID-19 in the province of British Columbia. A total of 75,255 of those individuals have recovered from the coronavirus, more than 300 patients remain hospitalized, and 1,365 British Columbians have perished due to COVID-19. The population of the western Canadian province is approximately 5.1 million.
Today, Hickman, spends a majority of her time in the laboratory doing whole genome sequencing of confirmed COVID-19 cases. The data she collects is used for outbreak response and for tracking new variants of the SARS-CoV-2 coronavirus that are appearing in different parts of the world. “It has been easily the most difficult year of my life, but also the most fulfilling,” she told the CBC. “What we have achieved here over the last year is huge.”
In their laboratory at the B.C. Centre for Disease Control in British Columbia, Canada, researchers Tracy Lee (above left) and Rebecca Hickman (above right) “are designing new tests to quickly identify variants of the COVID-19 virus,” North Shore News (NSN) reported. Now, wrote NSN, “the pair are working on a new type of ‘rapid test’ that will be able to detect ‘variants of concern’—particularly the U.K., South African, and Brazilian variants—at the same time as determining if a test is positive for COVID-19. When it’s finalized, that test is expected to dramatically speed up the process of hunting the variants.” (Photo copyright: North Shore News.)
Clinical Laboratories on the Front Lines
Last year, the American Society for Clinical Pathology (ASCP) produced a docuseries titled, “Laboratories on the Front Lines: Battling COVID-19” which highlighted the critical work clinical laboratories are doing to care for patients during the SARS-CoV-2 pandemic. The five-part series interviewed medical laboratory professionals across the US about their experiences during the pandemic.
In one episode, Stephanie Horiuchi, Clinical Microbiology Specialist at UCLA Health Systems, discussed how challenging and rewarding it has been working on the pandemic.
“Very long days. I’m not going to lie. Very, very long days, but it’s rewarding. I know the importance of what I am doing, and I know the importance of what needs to be done,” she said. “So, the time that I am here, it does go by very fast. You look up at the clock and you’re like oh, its 9pm. And then when I go home, it’s just eat and go to sleep and then rinse and repeat.
“I feel that this is a really important area of work that we all do as microbiologists,” Horiuchi continued. “And to just serve patients every day and to know that I am helping someone, it really warms my soul.”
In another episode of the docuseries, Professor of Pathology and Laboratory Medicine Alyssa Ziman, MD, Division Chief, Clinical Laboratory Medicine at UCLA Health, was interviewed regarding how they are coping with the increased demand for medical laboratory services.
“It’s been a really difficult and challenging time for our health system, for our laboratories, for our staff that are working through to provide the best possible patient care,” she said. Ziman is also Medical Director, Transfusion Medicine, at UCLA Health and Medical Director, Clinical Laboratories, at Ronald Reagan UCLA Medical Center. “Every day is a new challenge and a new way to adapt to changing rules from the CDC and from the LA County Public Health Department and to really evolve, so that we can continue to provide the testing that we have and continue to support our staff and our patients.”
Unsung Heroes of COVID-19
The COVID-19 pandemic has placed a strain on medical resources throughout the world. Clinical laboratory professionals are emerging as the unsung heroes of the crisis and the entire medical laboratory profession is receiving much deserved positive recognition for the crucial role laboratories are playing in fighting the pandemic.
Life After COVID: Positioning Your Lab for Success in a Post-Pandemic World FREE WebinarHeld Wednesday, March 31 at 1 PM EDT Now a Streaming Webinar! The SARS-CoV2 pandemic has had a profound impact on clinical laboratories. Across the globe, labs have been forced to rapidly adapt as the volume and breadth of testing dramatically shifted to support COVID-19 diagnostics. A 50-60% decline in the flow of routine specimens and revenues has been noted as higher value tests were...
