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The first family in Canada to have their genomes sequenced

The first family in Canada to have their genomes sequenced

15/06/2019
Posted by:

Dr.M.Raszek


Canada behind the world

In previous posts, we have commented on the future importance of families sequencing their genomes and preserving DNA information within the family. Currently however, genome sequencing for health screening is still uncommon, as the technology is still fairly new and not many people can yet grasp the value behind the test, so we are looking at a future trend. This likely will be even more evident in Canada where its citizens are accustomed to having access to public health that is publicly funded. For these reasons, Canada is further behind with the delivery of genomic medicine than other countries, as we have very few private outlets for it. While the genomic technology is trickling into Canadian medicine, and we have some landmark genomic centres in Canada, because it is a public healthcare system, any new technology has to be buried under a mountain of evidence before public money can be devoted for the use of this technology in the Canadian healthcare system. As a consequence, we are still not at the same level of genomic medicine use as we see in some other countries.

In addition, genomic medicine has its roots in diagnosing conditions that could not be identified with other available standard medical approaches. This approach eventually has paved the way to use this technology not just for diagnosing unknown conditions, but in order to check if any of such potential results could be found in any individual. The use of full genome sequencing for screening healthy people, is therefore still relatively new.

Nevertheless, thousands of presumed healthy people have already sequenced themselves, to learn about their potential predispositions, and even some families have already done so. So our dream of families collecting their genomic data, ideally accompanied by a detailed family medical history, has commenced.

But we do not know of any such examples in Canada.

Therefore Merogenomics is very proud to have participated in what we believe to be the first example of a Canadian family to have used full genome DNA sequencing for health screening purposes. This included 5 family members spanning three generations: a young husband and wife couple, both of the husband’s biological parents and a grandmother on his father’s side.

Image of Merogenomics article quote on family sequencing their genomes

 

Genome sequencing and how it all starts

This was a long educational journey to get to this point. It was a chance meeting with the husband of this family that started it all. However, he was already predisposed to the idea that the latest technology should be utilized to collect as much information as possible about oneself in order to benefit one’s health. This attitude definitely seems to run in the family, as the husband’s parents are already participating in the The Tomorrow Project. This a Canadian partnership, and is part of Alberta's Tomorrow Project, which involves more than 50,000 Albertans (the largest longitudinal study in the province’s history), and over 300,000 Canadians across Canada in a bid to understand why some people develop cancer and other chronic diseases, and others do not.

Image of Merogenomics article quote on what can cause cancer research

Next, the different family members (with the exception of the grandmother), came to public seminars hosted by Merogenomics about the benefits of genome sequencing, including one dedicated to personal screening (the category that this family falls into), and one that was dedicated to DNA sequencing in cancer. These seminars definitely pack a lots of background information in, and they are a great starting point towards becoming properly informed about the process of genome sequencing.

Once the family decided to take the genome sequencing test into serious consideration, a detailed educational process commenced via email. We do not make it simple as we do not wish to miss out on any of the test details. We have looked at many of the different guidelines that are related to the provision of genomic medicine for patients with undiagnosed diseases (there is very little information still related to the screening of healthy people), as one of the most important goals of Merogenomics in delivering full genome DNA testing access to clients is ensuring that their informed consent is truly based on being as thoroughly informed as possible. Basically you get a booklet’s worth of information.

Image of Merogenomics article quote on informed consent for genetic testing

The information we discuss in that lengthy communication process include the following topics:

  • Steps of obtaining the full genome sequence
  • The details about test deliverables details
  • The test delivery process and cost
  • What the test looks for
  • The benefits of the test
  • Test results protection
  • Test limitations
  • Payment options
  • Doctor considerations
  • Family considerations
  • Family history tools
  • Genetic counseling
  • Expected outcomes
  • Risks related to the return of the results
  • Future expected costs
  • The future uses of the obtained data
  • Considerations for reproductive decisions
  • Research involvement
  • Alternative testing options

As you can see, it is a lot of information! But full genome sequencing is not cheap, and it is very powerful technology with potentially serious consequences. We make sure we take the time for the clients involved to understand the value they will be investing in.

We then all met in person so that any remaining questions that any family member might have had could be answered, in case certain concerns were missed with the previous content provided, or anything might not have been clear. It is also an excellent opportunity to personally get to know potential clients. We met with the husband and wife couple, and then separately with the remainder of the family. Without a doubt, the show was stolen by the grandmother who, despite being in her 90’s, was full of life, full of smiles, charming, joking, and flaunting her quality genetics or quality lifestyle. While when it comes to genetics, time would tell, we did learn some secrets to her robust predisposition: she never smoked in her life, drank bit too much alcohol only once in her life, didn’t like it, and never drank alcohol again, follows strict healthy eating habits (with very little sugar exposure), and goes for a walk every single day, including pacing the length of her house if that is all that is available. We joked that it would have been nice to come and live with her for a while to use such an amazing role model to reinforce own hard-won health habits! All of us who had met grandma that afternoon for the first time, felt elevated by her positivity. The moment the family stepped out the door from the meeting, we were instantly “oohing and aaaahing” over how adorable she was.

 

DNA testing in old age

One question that was posed once the family had left: what is the benefit for someone her age to sequence her DNA? Her personal reasons to do it were not for herself, but to benefit the remainder of the family. Grandma has a medical background, and she understood the implications of leaving this type of treasure trove of information behind to benefit not only just her kids, but also grandkids and subsequent generations. That was her primary motivation.

Image of Merogenomics article quote on multi-generational benefits of DNA testing

Thus, if anything pathogenic were to be uncovered in grandma, this would help to inform one about how the genetic condition was inherited in the family, and if intervention were to be available for the condition, this could then point to which other family members should consider screening themselves for the same condition. In addition, even if no pathogenic information were uncovered, it leaves a genome behind for future analysis in case any of the descendants manifests some disease that is suspected to be of genetic origin. Having access to the genomes of multiple family members, along with their medical history, will allow for easier deciphering as to what may be the genetic root behind the condition.

In terms of the immediate benefits to herself, she was able to reap potentially very useful rewards, in learning how her DNA could inform how she should be handling certain medications. This is referred to as “pharmacogenetic information”. Currently when you are prescribed any medications, we actually have no way of knowing how they will affect you without doing some complicated bloodwork. The estimated average efficacy of a drug, you pop into your mouth or your vein is about 50%, so it is a coin toss as to whether the medication will truly be effective or not. DNA sequencing is going to be your best bet to get to the bottom of that, at least for some of the medications for which this information has been verified (for many it has not yet, so also beware of certain pharmacogenetic tests that try to outcompete one another by providing results for as many medications as possible, many of which might not have actual scientific validity, and therefore could be dangerous misinformation for doctors).

Image of Merogenomics article quote on medication efficacy

The medications from the top 200 prescribed drugs for which validated pharmacogenomic data exists include:

Allopurinol – used to decrease high blood uric acid levels to prevent gout, specific types of kidney stones, or a high uric acid level that can occur with chemotherapy

Amitriptyline – used to treat a number of mental illnesses that include major depressive disorders and anxiety disorders

Carbamazepine – an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain

Celecoxib – nonsteroidal anti-inflammatory drug used to treat the pain and inflammation in osteoarthritis, acute pain in adults, or rheumatoid arthritis

Citalopram – antidepressant drug used to treat major depressive disorders, obsessive compulsive disorder, panic disorder, and social phobia

Clopidogrel – antiplatelet medication used to reduce the risk of heart disease and stroke

Diclofenac – nonsteroidal anti-inflammatory drug used to treat pain and inflammatory diseases such as gout

Esomeprazole – medication which reduces stomach acid used to treat gastroesophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome

Excitalopram – antidepressant primarily used to treat major depressive disorders or generalized anxiety disorder

Methylphenidate – stimulant medication used to treat attention deficit hyperactivity disorder

Nortriptyline – used to treat depression, neuropathic pain, ADHD, anxiety, and as an aid to stop smoking

Omeprazole – used in the treatment of gastroesophageal reflux disease, peptic ulcer disease, and Zollinger–Ellison syndrome

Ondansetron – used to prevent nausea and vomiting caused by cancer chemotherapy, radiation therapy, or surgery

Paroxetine – antidepressant used to treat major depressive disorders, obsessive-compulsive disorder, panic disorder, social anxiety disorder, post-traumatic stress disorder, generalized anxiety disorder, and premenstrual dysphoric disorder

Sertraline – antidepressant used to treat major depressive disorders, obsessive–compulsive disorder, panic disorder, post-traumatic stress disorder, premenstrual dysphoric disorder, and social anxiety disorder

Simvastatin – lipid-lowering medication used to decrease elevated lipid levels and decrease the risk of heart problems in those at high risk

Warfarin – anticoagulant medication used to treat blood clots such as deep vein thrombosis and pulmonary embolism and to prevent strokes in people who have atrial fibrillation, valvular heart disease, or artificial heart valves

If you are on any of the medications listed above, you actually might benefit from looking into how your DNA might help you with regards to how the medication you are taking should be dosed for you for the best possible effect.

The same would apply to our grandma, if she happens to take any medications that already have validated pharmacogenetic information associated with it. What are the odds that one of the medications she is taking will have pharmacogenetic information tied to it? Probably pretty high!

According to Statistics Canada, 41% of all Canadians take some medication. For those that are 65 years of age and older, that number skyrockets to almost 83%, and many of our seniors take multiple medications at the same time. The top 5 prescriptions for senior women include lipid-modifying agents, drugs for peptic ulcer and gastro-oesophageal reflux disease, thyroid medication, ACE inhibitors to lower blood pressure, and Beta-blocking agents to manage abnormal heart rhythms.

Image of Merogenomics Blog Figure on Canada Medication Use

Adapted from Rotermann M et al. 2014. Health Rep 25(6):3-9

Considering that one study suggested that nearly 44% of all emergency hospital visits are related to the adverse effects of medication, any ill-effects from inadvertent medication use at such an advanced age can have serious consequences.

So while grandma was motivated by providing information for the future benefit of her family, there could be direct benefits for herself as well.

What about the other family members?

Their incentive was the hunger for knowledge about themselves. Everyone could benefit if some pathogenic information was uncovered for which intervention was available. Even if no intervention was available, there are other benefits to early knowledge such as health management, preparation, or even clinical trial considerations. The young couple could benefit from knowing if their carrier status matches. These are recessive mutations, meaning both parents have to contribute a mutant copy for a child to develop a disease. Almost everyone is a carrier of some such recessive mutations. Finally, everyone can benefit from getting pharmacogenetic information to determine how certain medications should be dosed, or whether they could be toxic or not. We have previously recounted the benefits of genome sequencing.

Soon after our in-person meeting the family decided to pull the trigger, and all five members of the three generation lineage would be sequencing themselves!

 

Genetic testing and insurance

The next step was deciding who would be the doctor(s) that would sign off for the test and oversee the results. Every single person had their own family physician, which would have been equated to a lot of doctor visits and signatures to collect! In the end, the family decided to go with one doctor for everyone, and one that was recommended by Merogenomics, so a new doctor for everyone! This was done out of convenience and for the ease of moving forward, but there was another added benefit. While insurance companies in Canada are barred from collecting genetic information for appraisal, they can request all other medical information from the doctor. Thus, if a doctor chooses to incorporate genomic results into a patient’s medical record, that information has to be labelled so as not to ever be accidentally provided to the insurance companies. But such mistakes can happen.

However, insurance companies can only collect medical information from your primary family physician. Therefore if a physician other than your family doctor is overseeing your genome DNA test results, it is yet another step away from the possibility that an insurance company could get their hands on your genetic results.

Not that they would want to, as it would create more of a headache for them than anything else!

Since the introduction of the anti-genetic discrimination law, there is not yet a clear interpretation of that law in court. Insurance companies are certainly not eager to be the guinea pigs and face the stiff fines. Since they are already using the family history for their actuarial valuations, and no one yet knows how access to genetic information would provide any additional benefit, in the face of the stiff legal repercussions, insurance companies make it very clear on their applications for health-related policies that genetic information is not to be submitted. And as for that question which asks whether there were any other tests that the insurance company should know about that might impact the outcome of a policy’s approval, again, genetic testing or any DNA sequencing testing is exempt from the information that is expected to be provided to the insurance companies.

Image of Merogenomics article quote on DNA testing and insurance

Thus, if an insurance company were to accidentally receive results of genomic testing from a doctor, then it is just a hassle for them. They have to then inform the doctor and the policy holder that the information was received, not used or even viewed, and destroyed. But if any claim is later denied, then from then on, in theory it exposes the company to legal liability for potential genetic discrimination. It is much easier for insurance companies at the moment to simply just avoid any access to genetic information altogether.

Therefore, if you go with a different doctor other than your family doctor, you just reduce that chance and avoid such a headache. That is exactly what this family did.

The family got the full genome test requisition forms signed off by the doctor all in one go. Since this was a clinical test, the physician’s consent is required for regulatory compliance, primarily to ensure patient safety and that the test results are appropriately applied towards medical management, including the context of family medical history. This is not trivial and requires appropriate medical experience. With test orders signed by the doctor, sample collection kits with pre-paid shipping labels were on their way, and a second email was sent off detailing the process of sample collection and the sample shipping protocol.

The next step was collecting the samples. Two options are available, either saliva or blood. Both can provide equally accurate results, although marginal benefits can be ascribed to blood samples. The entire family elected for blood samples and appropriate kits with collection tubes were provided for each family member, with their own identification code that matched the code on the test requisition form. We really wanted to make sure that every family member was appropriately matched to their own kit, and had their own collection tubes so that no accidental sample swapping would occur. With that many family members all testing at the same time, it is possible that such an occurrence could happen!

The procedure of shipping of human blood, a biohazardous material, has very specific requirements. It can seem confusing and Merogenomics certainly wants to make sure the process is done accurately, as failure to follow this step correctly could delay the entire process. But the blood samples were soon on their way to a laboratory in the US, where the samples would next be processed for DNA isolation, checked for quality control, and sequenced to collect the precious personal DNA code that is the unique blueprint comprising each of the family members. This can be a lengthy process, and everyone was curious about what would be uncovered for this first Canadian family to screen their health predispositions with a full genome test. It was a very eagerly awaited moment, and what were the results will be discussed in another post to follow.

If you are a family that is interested in delving into the world of medical genomics, Merogenomics can assist you with the entire process. There is no additional cost to you for this great service, as the payment is made by the service provider and not the client. The test will cost you the same whether you involve Merogenomics to help you along the way or not, but your education towards informed consent will be beyond what any service provider will manage to offer.

 

This article has been produced by Merogenomics Inc. and edited by Kerri Bryant. Reproduction and reuse of any portion of this content requires Merogenomics Inc. permission and source acknowledgment. It is your responsibility to obtain additional permissions from the third party owners that might be cited by Merogenomics Inc. Merogenomics Inc. disclaims any responsibility for any use you make of content owned by third parties without their permission.

 

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