Clinical laboratory managers should note that this company’s new diagnostic offering involving screening embryos for specific genetic conditions is not without controversy
Is the world ready for whole genome sequencing (WGS) of preimplantation embryos to help couples undergoing in vitro fertilization (IVF) treatments know if their embryos have potential genetic health problems? Orchid Health, a clinical preimplantation genetic testing (PGT) laboratory that conducts genetic screening in San Francisco, believes the answer is yes! But the cost is high, and the process is not without controversy.
According to an article in Science, Orchid’s service—a sequencings of the whole human genome of preimplantation embryos at $2,500 per embryo tested—“will look not just for single-gene mutations that cause disorders such as cystic fibrosis, but also more extensively for medleys of common and rare gene variants known to predispose people to neurodevelopmental disorders, severe obesity, and certain psychiatric conditions such as schizophrenia.”
However, Science also noted that some genomics researchers “claim the company inappropriately uses their data to generate some of its risk estimates,” adding that the “Psychiatric Genomics Consortium (PGC), an international group of more than 800 researchers working to decode the genetic and molecular underpinnings of mental health conditions, says Orchid’s new test relies on data [PGC] produced over the past decade, and that the company has violated restrictions against the data’s use for embryo screening.”
There are some who assert that a whole genome sequence of an embryo—given today’s state of genetic technology and knowledge—could generate information that cannot be interpreted accurately in ways that help parents and doctors make informed prenatal testing decisions. At the same time, criticisms expressed by the PGC raise reasonable points.
Perhaps this is a sign of the times. Orchid Health is the latest genetic testing company that is looking to get ahead of genetic testing competitors with its diagnostics offerings. Meanwhile, knowledgeable and credible experts question the appropriateness of this testing, given the genetic knowledge that exists today.
“This is a major advance in the amount of information parents can have,” Orchid’s founder and CEO Noor Siddiqui (above) told CNBC. “The way that you can use that information is really up to you, but it gives a lot more control and confidence into a process that, for all of history, has just been totally left to chance.” Should Orchid Health’s analysis prove useful, pediatricians could order further clinical laboratory prenatal testing to confirm and diagnose potential genetic diseases for parents. (Photo copyright: General Assembly.)
Orchid Receives World-class Support
Regardless of the pushback from some genetic researchers, Orchid has attracted several world-class geneticists and genetics investors to its board of advisors. They include:
Jacques Cohen, PhD, embryologist, co-founder and former director for genetics laboratory Reprogenetics LLC (now CooperGenomics).
Anne Wojcicki, co-founder and CEO of direct-to-consumer genetic testing company 23andMe.
and others.
The WGS test, according to Orchid, detects genetic errors in embryos that are linked to severe illnesses before a pregnancy even begins. And by sequencing 99% of an embryo’s DNA, the test can spot potential health risks that could affect a future baby.
According to its website, the PGT lab company uses the WGS data to identify both monogenic (single-gene) and polygenic (multiple-gene) diseases, including:
Orchid is not without its critics. Knowledgeable, credible experts have questioned the appropriateness of this type of genetic testing. They fear it could become a modern-day form of eugenics.
Andrew McQuillin, PhD, Professor of Molecular Psychiatry at University College London, has concerns about Orchid’s preimplantation genetic testing. He maintains that it is difficult to control how such data is used, and that even the most accurate sequencing techniques do not predict disease risk very well.
“[Polygenic risk scores are] useful in the research context, but at the individual level, they’re not actually terribly useful to predict who’s going to develop schizophrenia or not,” McQuillin told Science. “We can come up with guidance on how these things should be used. The difficulty is that official guidance like that doesn’t feature anywhere in the marketing from these companies.”
McQuillin also stated that researchers must have an extensive discussion regarding the implications of this type of embryo screening.
“We need to take a look at whether this is really something we should be doing. It’s the type of thing that, if it becomes widespread, in 40 years’ time, we will ask, ‘What on Earth have we done?’” McQuillin emphasized.
Redefining Reproduction
It takes about three weeks for couples to receive their report back from Orchid after completing the whole genome sequence of a preimplantation embryo. A board-certified genetic counselor then consults with the parents to help them understand the results.
Founder and CEO Noor Siddiqui hopes Orchid will be able to scale up its operations and introduce more automation to the testing process to the cost per embryo.
“We want to make this something that’s accessible to everyone,” she told CNBC.
“I think this has the potential to totally redefine reproduction,” she added. “I just think that’s really exciting to be able to make people more confident about one of the most important decisions of their life, and to give them a little bit more control.”
Clinical laboratories have long been involved in prenatal screening to gain insight into risk levels associated with certain genetic disorders. Even some of that testing comes with controversy and ambiguous findings. Whether Orchid Health’s PGT process delivers accurate, reliable diagnostic insights regarding preimplantation embryos remains to be seen.
Research findings could lead to new biomarkers for genetic tests and give clinical laboratories new capabilities to diagnose different health conditions
New insights continue to emerge about “junk DNA” (aka, non-coding DNA). For pathologists and clinical laboratories, these discoveries may have value and eventually lead to new biomarkers for genetic testing.
One recent example comes from researchers at Stanford Medicine in California who recently learned how non-coding DNA—which makes up 98% of the human genome—affects gene expression, the function that leads to observable characteristics in an organism (phenotypes).
The research also could lead to a better understanding of how short tandem repeats (STRs)—the number of times a gene is copied into RNA for protein use—affect gene expression as well, according to Stanford.
“We’ve known for a while that short tandem repeats or STRs, aren’t junk because their presence or absence correlates with changes in gene expression. But we haven’t known how they exert these effects,” said study lead Polly Fordyce, PhD (above), Associate Professor of Bioengineering and Genetics at Stanford University, in a news release. The research could lead to new clinical laboratory biomarkers for genetic testing. (Photo copyright: Stanford University.)
To Bind or Not to Bind
In their Science paper, the Stanford researchers described an opportunity to explore a new angle to transcription factors binding to some sequences, also known as sequence motifs.
“Researchers have spent a lot of time characterizing these transcription factors and figuring out which sequences—called motifs—they like to bind to the most,” said the study lead Polly Fordyce, PhD, Associate Professor of Bioengineering and Genetics at Stanford University, in a Stanford Medicine news release.
“But current models don’t adequately explain where and when transcription factors bind to non-coding DNA to regulate gene expression. Sometimes, no transcription factor is attached to something that looks like a perfect motif. Other times, transcription factors bind to stretches of DNA that aren’t motifs,” the news release explains.
Transcription factors are “like light switches that can turn genes on or off depending on what cells need,” notes a King’s College LondonEDIT Labblog post.
But why do transcription factors target some places in the genome and not others?
“To solve the puzzle of why transcription factors go to some places in the genome and not to others, we needed to look beyond the highly preferred motifs,” Fordyce added. “In this study, we’re showing that the STR sequence around the motif can have a really big effect on transcription factor binding, providing clues as to what these repeated sequences might be doing.”
Such information could aid in understanding certain hereditary conditions and diseases.
“Variations in STR length have been associated with changes in gene expression and implicated in several complex phenotypes such as schizophrenia, cancer, autism, and Crohn’s disease. However, the mechanism by which STRs affect transcription remains unknown,” the researchers wrote in Science.
Special Assays Explore Binding
According to their paper, the research team turned to the Fordyce Lab’s previously developed microfluidic binding assays (MITOMI, k–MITOMI, and STAMMP) to analyze the impact of different DNA sequences on transcription factor binding.
“In the experiment we asked, ‘How do these changes impact the strength of transcription factor binding?’ We saw a surprisingly large effect. Varying the STR sequence around a motif can have a 70-fold impact on the binding,” Fordyce wrote.
In an accompanying Science article titled, “Repetitive DNA Regulates Gene Expression,” Thomas Kuhlman, PhD, Assistant Professor, Physics and Astronomy, University of California, Riverside, wrote that the study “demonstrates that STRs exert their effects by directly binding transcription factor proteins, thus explaining how STRs might influence gene expression in both normal and diseased states.”
“This research unveils, for the first time, the intricate connection between how variants in the non-coding genome affect genes that are associated with blood pressure and with hypertension. What we’ve created is a kind of functional map of the regulators of blood pressure genes, “said Philipp Maass, PhD, Lead Researcher and Assistant Professor Molecular Genetics, University of Toronto, in a news release.
The research team used massively parallel reporter assay (MPRA) technology to analyze 4,608 genetic variants associated with blood pressure.
The findings could aid precision medicine for cardiovascular health and may possibly be adopted to other conditions, according to The Hospital for Sick Children.
“The variants we have characterized in the non-coding genome could be used as genomic markers for hypertension, laying the groundwork for future genetic research and potential therapeutic targets for cardiovascular disease,” Maass noted.
Why All the ‘Junk’ DNA?
Clinical laboratory scientists may wonder why genetic research has primarily focused on 20,000 genes within the genome, leaving the “junk” DNA for later investigation. So did researchers at Harvard University.
“After the Human Genome Project, scientists found that there were around 20,000 genes within the genome, a number that some researchers had already predicted. Remarkably, these genes comprise only about 1-2% of the three billion base pairs of DNA. This means that anywhere from 98-99% of our entire genome must be doing something other than coding for proteins,” they wrote in a blog post.
“Imagine being given multiple volumes of encyclopedias that contained a coherent sentence in English every 100 pages, where the rest of the space contained a smattering of uninterpretable random letters and characters. You would probably start to wonder why all those random letters and characters were there in the first place, which is the exact problem that has plagued scientists for decades,” they added.
Not only is junk DNA an interesting study subject, but ongoing research may also produce useful new biomarkers for genetic diagnostics and other clinical laboratory testing. Thus, medical lab professionals may want to keep an eye on new developments involving non-coding DNA.
NIH program could lead to new diagnostic biomarkers for clinical laboratory tests across a more diverse segment of US population
In another milestone in the US National Institutes of Health’s (NIH) plan to gather diverse genetic information from one million US citizens and then use that data to inform clinical care in ways consistent with Precision Medicine, the NIH’s All-of-Us Research Program announced in a news release it has “begun returning personalized health-related DNA results” to more than 155,000 study participants.
In addition, those participants who request them will receive genetic reports that detail whether they “have an increased risk for specific health conditions and how their body might process certain medications.”
The All-of-Us program, which began enrolling people in 2018, is one of the world’s largest—if not the largest—project of its kind. It could result in more than a million human whole genome sequences to drive medical research and speed discoveries. Study findings, for example, may produce new biomarkers for clinical laboratory tests and diagnostics.
In 2020, the All-of-Us program “had begun releasing genetic results for ancestry and a small number of nonclinical genetic traits,” according to GenomeWeb. Now, the program is taking on the greater challenge of sharing health-related genetic test results directly with its participants.
“We really wanted to make sure that we are providing a responsible return to our participants,” Anastasia Wise, PhD, All-of-Us Program Director for the Genetic Counseling Resource, told GenomeWeb. “They might get information that’s unexpected,” she explained.
So far, about 10,000 people received the NIH’s invitation and 56% have shown interest in receiving their genetic test results, GenomeWeb noted.
“Knowledge is powerful,” said Josh Denny, MD (above), Chief Executive Officer, NIH All-of-Us Research Program, in an NIH news release. “By returning health-related DNA information to participants, we are changing the research paradigm, turning it into a two-way street—fueling both scientific and personal discovery that could help individuals navigate their own health,” he added. The NIH’s research could lead to new clinical laboratory precision medicine diagnostics for chronic diseases across a more diverse segment of the US population. (Photo copyright: National Institutes of Health.)
Two Types of Genetic Health Reports
Study participants who provided a blood sample and gave their consent to receiving genomic information may also receive a Hereditary Disease Risk report that includes 59 genes and genetic variants linked to serious and “medically actionable” health conditions.
About 3% to 5% of participants will have findings suggesting a high risk for a genetic disease such as breast and ovarian cancers as indicated by BRCA1 and BRCA2 genes, Medical Xpress reported.
“I kind of shudder to think about what could happen if I hadn’t known this [finding that she has the BRCA2 gene],” said Rachele Peterson, All-of-Us Chief of Staff, who spoke to the Associated Press about her receiving own Hereditary Disease Risk report.
Participants can also choose to receive an All-of-Us Medicine and Your DNA report with insights on seven genes that affect how specific medications are metabolized. This pharmacogenetics report is important for those who could learn, for example, that they have a 50% to 60% greater risk of a second heart attack when they continue to take the standard medication, as opposed to a different medication, Medical Xpress noted.
“The information on metabolizing medication can be particularly important for people who need treatment after a heart attack,” Josh Denny, MD, Chief Executive Officer, NIH All-of-Us Research Program, told Medical Xpress.
“Such transparency of genetic information about a massive group—as well as the genetic information on individuals—can be used to improve patient care and clinical outcomes,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report.
“The program provides a roadmap for other healthcare organizations to follow. And this is useful strategic knowledge for clinical laboratory leaders to understand and incorporate into their plans to support precision medicine with genetic testing and whole human genome sequencing,” Michel added.
Rich Genetic Data Across a More Diverse Population
As to its goal to reflect national diversity, NIH reported about 80% of All-of-Us participants reside in communities that have been unrepresented in medical research, and that 50% are part of a racial or ethnic minority group.
By combining this information into a single database, the MVP promises to advance knowledge about the complex links between genes and health, according to an MVP news release.
Researchers tapping All-of-Us and MVP data may ultimately produce enlightening and impactful study findings, which could enable clinical laboratories to perform new diagnostic precision medicine tests that identify diseases early and save lives.
Goal is to demonstrate how whole human genome sequencing of newborns can deliver important diagnostic findings associated with 250 genetic conditions
Clinical laboratory testing and genetics are moving closer to the delivery room than ever before. In the largest study of its kind in North America, genomic scientists plan to supplement traditional screening for inherited diseases—traditionally performed on a blood sample taken shortly after birth—with whole genome sequencing (WGS) on 100,000 newborns in New York City during their first five years of life, LifeSciencesIntelligence reported.
Conducted by genetic scientists at NewYork-Presbyterian (NYP) and Columbia University, in collaboration with genetic company GeneDx, a wholly-owned subsidiary of health intelligence company Sema4 (NASDAQ:SMFR), the genetic research study, called GUARDIAN (Genomic Uniform-screening Against Rare Diseases In All Newborns), will screen newborn babies for 250 rare diseases that are generally not tested for.
The GUARDIAN program will “drive earlier diagnosis and treatment to improve the health of the babies who participate, generate evidence to support the expansion of newborn screening through genomic sequencing, and characterize the prevalence and natural history of rare genetic conditions,” according to a Sema4 news release.
“The appetite for this is growing. The awareness of this is growing. We all see it as inevitable,” medical geneticist Robert Green, MD, at Brigham and Women’s Hospital and Harvard Medical School told USA Today. “We are grossly underutilizing the life-saving benefits of genetics and we have to get past that.” Clinical laboratory leaders understand the value of early detection of disease and subsequent early treatment. (Photo copyright: Harvard Medical School.)
Improving Health of Babies Through Early Detection of Disease
GUARDIAN aims to use WGS to identify conditions at birth that can affect long-term health and subsequently enhance treatment options and possibly prevent disability or death.
The 250 different diseases GUARDIAN will be screening for typically strike young children. They are mostly rare conditions that:
have an onset before five years of age,
have a greater than 90% probability of the condition developing based on the genetic result,
have effective approaches and treatments that are already available, and/or
have a well-established natural history of the condition.
“We’re entering the therapeutic era and leaving the diagnostic era,” Paul Kruszka, MD, Chief Medical Officer at GeneDx told USA Today. “This potentially has the opportunity to change the way we practice medicine, especially in rare disease.”
Some Parents Reluctant to Agree to Genetic Testing
Green and his research team first began analyzing the genetic sequences of newborns back in 2013. They believe the costs of performing infant WGS is worthwhile because it can improve lives. However, Green also recognizes that some parents are reluctant to agree to this type of genetic testing due to concerns regarding privacy and the fear of discovering their baby may have an illness.
“You’ve gone through all this pregnancy and you’re sitting there with a healthy baby (and I’m) offering you the opportunity to find out something that’s devastating and terrifying,” he told USA Today. “How fun is that?”
Green continued. “We can respect people who don’t want to know, but also respect people who do want to know. Some families will say ‘I treasure the precious ignorance.’ Others will say ‘If I could have known, I would have poured my heart and soul into clinical trials or spent more time with the child when she was healthy.’”
WGS Screening Identifies Undiagnosed Illnesses in Newborn’s Family
The scientists also found that performing WGS in newborns can detect diseases in the infants as well as unknown illnesses in the families of those babies. According to Kruszka, many parents often seek a diagnosis for a rare disease present in their children for several years. Since many common diseases develop as a result of certain combinations of genes, if illnesses are diagnosed at birth, it could extradite the treatment process, prevent complications, and provide better health outcomes for patients.
“We are relentlessly focused on accelerating the adoption and use of genomic information to impact the lives of as many people as possible, particularly newborns and children,” said Katherine Stueland, President and CEO, Sema4, in the Sema4 news release. “As the first commercial laboratory to launch a rapid whole genome sequencing offering, to address broad unmet needs for early diagnosis, participation in this study is an important step forward for healthcare and in delivering on our goal to sequence once, analyze forever.”
The study is open to all babies in New York City who are born in a health system that participates in the GUARDIAN program, regardless of their race, income, or health insurance coverage.
“The results from this study will help us understand the true impact sequencing at birth can have on newborns and their families in comparison to the current standard of care, particularly as we’ll evaluate clinical outcomes in addition to the psychosocial effect on families,” said Kruszka in the Sema4 news release.
Anything that improves the health of newborn babies is a good thing. Regardless of the cost, if DNA analysis can give newborns and their families a better chance at detecting inherited diseases early while clinical laboratory treatment could make a difference, it is worth pursuing.
Genetic testing for the health and wellbeing of beloved pets is not unlike clinical laboratory testing to develop personalized treatments for humans
Clinical laboratory professionals know that the same patients who complain about a $10 copay for their own laboratory testing will happily pay veterinarians tons of cash to test and treat their beloved pets. And as genetic testing for humans becomes commonplace, more people are seemingly willing to pay for genetic analyses of their pets as well.
In June, animal health company Zoetis, Inc. announced it had completed the acquisition of pet care genetics company Basepaws. The financial terms of the deal were not disclosed.
California-based Basepaws is a privately-held company that provides pet owners with analytics, genetic tests, and early health risk assessments for their pets through oral microbiome analysis. Founded in 2017, Basepaws was responsible for the creation of the first at-home genetic testing platform for cats.
Basepaws sells easy-to-use genetic testing kits for cats that allow pet owners and veterinarians to better understand an individual pet’s predisposition to certain illnesses and increase the likelihood of early detection and treatment of those diseases.
It’s not unlike the drive toward personalized medicine and genetic testing that is at the core of human precision medicine.
Different Breeds, Different Needs
Basepaws has a slogan: “Different breeds, different needs.” This means, according to their website, each individual cat has a unique composition of genetic traits that can relate to its needs for optimal health and wellbeing. Obviously, this would apply to all pets.
“As a pioneer in pet care genetics, the California-based Basepaws offers easy-to-use genetic screening tools for the early detection of disease risk in pets, as well as individualized breed and health reports that can identify traits, biomarkers, and potential hereditary conditions for pets. Basepaws helps pet owners and veterinarians understand an individual pet’s risk for disease and can lead to more meaningful engagements and increased likelihood of early detection and treatment of disease,” states a Zoetis press release announcing the acquisition.
“The addition of Basepaws will enhance our portfolio in the precision animal health space and inform our future pipeline of pet care innovations,” said Kristin Peck, CEO of Zoetis, in the press release. “Working together, we can continue to provide veterinarians and pet owners with more comprehensive ways to proactively manage the health, wellness, and quality of care for their animals.”
“Basepaws and Zoetis both consist of pet lovers with a passion for science, and our mission is to create better and longer lives for our pets through knowledge and data,” Anna Skaya (above), CEO of Basepaws, told ROI-N.J. “We look forward to expanding our business and the impact of our genetic products with the global scale and [research and development] experience of Zoetis, the world leader in animal health. We believe that, together, we can bring the benefits of a more proactive healthcare approach to pet parents around the world.” Genetic testing for optimum pet health is not unlike the drive for personalized clinical laboratory genetic testing for humans. (Photo copyright: Los Angeles Times.)
Test Results for Hundreds of Genetic Disorders and Health Markers
Basepaws currently sells three DNA test kits for felines on their webpage. The current price for an oral health test kit that identifies active signs of dental diseases is $69. Their breed and cat health DNA test kit, which provides results for over 115 known feline genetic markers, is $129. Their most comprehensive testing kit is a whole genome sequencing (WGS) kit which is currently on sale for $399.
After receiving a test kit by mail, the purchaser registers the kit online, takes a single buccal swab from their kitty’s inner cheek, and then mails the sample to Basepaws. Lab personnel then extract the cat’s DNA from the sample and perform quality checks to ensure the sample is acceptable for genetic testing. It takes four to six weeks for consumers to receive test results.
According to the company’s website, Basepaws’ WGS test provides results related to 43 genetic disorders that are represented by 65 health markers. The listing of genetic disorders contained in the Health Marker section of the Basepaws report includes data on:
Metabolic disorders,
Musculoskeletal and connective tissue disorders,
Renal disorders,
Cardiovascular disorders,
Blood disorders,
Eye disorders,
Endocrine disorders,
Skin disorders, and
Autoimmune disorders.
“The Basepaws team has done an amazing job demonstrating how genetic testing and data can improve how we care for the pets in our lives,” Abhay Nayak, Executive Vice President at Zoetis, told ROI-NJ. “With the addition of Basepaws, Zoetis will continue to strengthen our portfolio of products for precision animal health, across genetics, diagnostics, and data analytics for pets and livestock. We are also excited by how Basepaws’ feline genomic and microbiome database will help enhance our [research and development] capabilities and inform the future of our pet care pipeline.”
Zoetis, based in Parsippany, N.J., manufactures vaccines, medicines, clinical laboratory diagnostics, and other technologies for the benefit of companion pets and livestock. The Fortune 500 company generated $7.8 billion in revenue in 2021, according to its website.
The article also stated that the global animal genetic testing market was valued at $990 million in 2020 and is only expected to rise.
Thus, spending money keeping our pets healthy is not only a typical element of Americans’ lives, but also a mega-billion-dollar industry. With at-home genetic testing for humans increasing in popularity, it’s likely testing for animals will follow that trend as well.
In the future, some clinical laboratory organizations may want to consider assessing the animal DNA testing market for its potential to be a useful source of new revenue, especially because potential customers will pay cash when they order genetic tests for their dogs and cats.
