Our lab is now ISO-13485 certified. Let me assure you that a lot of hours went into this.
If you for any reason, need a lab to make you a molecular biology diagnostic test, we’re the ones to call.
Despite some ridiculous legal obstacles in this country, we are finally able to set up some proper genetic tests. I need to update myself on these tests – and what better way than to do it while blogging about them at the same time.
We are setting up 8 tests in this first stage of expansion, which I plan to cover in 5-6 posts.
1. Familal Hypercholesterolemia. A disease leading to highly elevated levels of cholesterol and increased risk of heart disease (good review here). Rough numbers: heterozygosity 1:500, homozygosity 1:1000000. Multiple genetic variations (SNPs, insertions/deletions) in LDL-receptor gene. Preferred analytical method: sequencing or genotyping (real-time PCR) a selection of genetic variants.
Normal function of the hepatic low-density lipoprotein (LDL) receptor is obligate for normal levels of plasma LDL cholesterol. The LDL receptor regulates the concentration of plasma LDL cholesterol by internalizing apolipoprotein B-100- and apolipoprotein E-containing lipoproteins by receptor-mediated endocytosis. Mutations in the gene encoding the LDL receptor protein give rise to one of the most common classical autosomal dominant inherited disorders in man, familial hypercholesterolemia (FH). The estimated prevalence of heterozygous FH is 0.2% (1:500) in most populations of the world. – from here
In addition to LDL-receptor mutation analysis (which will take a little while to set up) we’ll be doing SNP-analysis for ApoB-100. One SNP-assay of R3500Q in the ApoB-100 gene.
Familial defective apolipoprotein B (FDB) caused by the R3500Q apolipoprotein B gene mutation may mimic FH but the clinical course, however, is often milder than that seen in patients with LDL receptor gene mutations. -from here
Tests to follow: Thrombophilia, Hemochromatosis, Lactose intolerance, Osteoporosis, Macular degeneration and Crohn’s Disease.
The following is my response to this Mary Meets Dolly post on prediagnostic genetic testing for Downs Syndrome.
To add some facts arguing against your view on genetic testing for Downs syndrome:
In my home country, where the right to abortion has been established many, many years and where every women (public healthcare) over the age of 38 is offered genetic testing for trisomy 21, the number of children born with Downs has remained unchanged also after the introduction of genetic testing. Thus, your assumption that this testing leads to less children born with this syndrome may not hold true. Also, I do not think that most people believe that the world would be a better place without Downs. I think however, that most people understand that this is a severe disease and that life with Downs is a challenge for the family as a whole. As for the lessons of life, it is truly sad when someone says that we need the sick and disabled to learn these lessons. Such a statement demeans these patients by saying they function as tools for us to understand the less fortunate.
I once thought overselling science was the biggest threat to scientific credibility. Credibility scientists need to achieve general acceptance in the public, and subsequently continued funding (progress).
Recent developments have made me think that rushing into commercializing new biomedical technology, like embryo sorting and genetic testing may pose a larger threat. Examples are genetic tests for athletic ability and embryo sorting based on more or less uncertain predictions of phenotypes without medical significance.
Granted, athletic testing and embryo sorting will not become a reality for most of us for a long long time. Athletic ability one can usually assess wit the naked eye, and having sex to create offspring is far too much fun for it to go away.
- Then all the more reason to pause and think twice before unleashing commercial products to the unsuspecting and unschooled (in genetics) lay man. Even more reason to pause, when those products have disputable accuracy and are of questionable value
These are the early days of the genomic era, there are many, many things we still do not know, especially when it comes to the nature vs. nurture relationships. Since the future keeps evading finite predictability, absolute disease risks (or any other risks or absolute probabilities for that matter) within the full time span of a human life, remains utopic.
We are moving in the right direction, all-encompassing disease prevention and/or treatment is on the horizon together with increased longevity.
Let’s not screw it up for ourselves. Our credibility is all we have, – please people show some restraint…..
[Jacques] Cohen [research director at Reprogenetics, a genetic-testing company in West Orange, New Jersey] says that as the understanding of disease genetics progresses, use of tests that seem controversial now may become more acceptable in the future: “If you had the chance to decrease your child’s risk of a disease like diabetes and you didn’t, society would blame you.“
So much is wrong with this statement.
First he is taking the focus away from the very real and disturbing issue of embryo-sorting based on uncertain risk estimation of predisposition to complex disease.
Secondly his statement underscores the importance of the environmental factor in such complex diseases, but it completely misses the point. If you want your children to avoid diabetes, then make them eat right and exercise. You can do that today without any knowledge of their genetics.
Thirdly, currently, society doesn’t seem to blame parents that neglect their children’s health by feeding them unhealthy food or fail to encourage (enforce) physical activity, – why would a genetic test change that.
Lastly, putting such blame on parents has some very problematic socio-ethical issues attached to it.
I hope this is an example of misquoting, I really do….
Image via Wikipedia
A lot has been said about (and argued over) Direct To Consumer (DTC) testing. For extensive coverage of the pros and cons of regulation of such genetic testing please go see The Gene Sherpa and Genetic Future (also, check out a number of recent papers in Nature, – to find them, go read the relevant posts at The Genetic Genealogist or Genetic Future). I have voiced opinions on this too, but have decided to desist more arguing (for a while) after reading this editorial in Nature biotechnology:
1. We need to move from late to early diagnosis
It is virtually impossible to conceive of a sustainable form of healthcare that operates as the current systems in industrialized nations do. At present, healthcare is based on the late diagnosis of disease and the division of diseases into a few categories based on some overarching gross similarities. And it firmly places physicians as the central gatekeepers of information.
2. To do this we need find ways to utilize the potential unleashed by large scale analysis of genetic-material.
The healthcare of the future, on the other hand, if the technical potential to provide personalized medicine is ever to be realized, will probably require a greatly expanded emphasis on diagnosis and monitoring, early and subtle intervention, monitoring of the impact of intervention, and gradual adaptation of treatment with the evolving physiology, metabolism and lifestyle of the individual.
3. But, the medical professionals and healthcare systems do not currently have the capacity to adequately respond.
Faced with this huge expansion of data on ‘my’ health, it will simply not be affordable to maintain our dependence on medical gatekeepers, whether they are physicians or genetic counselors, without individuals taking a much greater responsibility for their own wellbeing. Whether the medical establishment likes it or not, it will be too cumbersome and too expensive to conduct personalized medicine if all diagnostic-to-therapeutic decisions depend on doctors.
4. Therefore, In order to adapt to this new situation, we need to find the golden mean between no regulation and over-regulation.
For personal genomics not to be stillborn, the medical community and regulators thus need to reevaluate their role as gatekeepers. Clearly, they need to be involved in the medical actions that might follow as a consequence of genetic or other diagnostic testing. And for any gene test, regulators must ensure that companies make claims to consumers that are both truthful and accurate. But simply shutting down the whole direct-to-consumer gene testing enterprise because it departs from the traditional genetic testing paradigm of doctorordered test will both retard progress and stifle investment in more advanced whole-genome sequencing technologies—technologies that have the potential to ultimately deliver the promise of genomedirected medicine.
Regulation is obviously needed at some level. However, I reside in a country where regulation completely stifles any attempt to do personalized medicine, even at the most innocent (Cyp 450) level. I strongly advise against such an approach. Transferring all testing currently offered by DTC companies, to existing health-care programs will flood the system, and hence is not an option either.
In my opinion, there is an imminent need to define the subgroup of genetic tests that needs to be accompanied by counseling/medical advice. Group those out sensibly, grade them according to counseling importance, and you have a solution.
I have three children. I know them very well. Every parent should. I know that they have strengths, – some things they do very well (they know it too). I know that they struggle with other things (they are aware of this too). I tell them to tell me if I can help them learn something new or manage something they find complicated. I encourage them when I see that they are enjoying something they are good at. I tell them that it does not matter if there are things they do not master, – everyone can’t be good at everything I tell them. They accept that. We all do.
I can see if they are sick or are feeling unwell. I tell them to tell me if they feel sick or uncomfortable for some reason. I tell them I will do my best to make them well again. I comfort them and tell them that this will pass, and you’ll be fit as a fiddle again soon. I tell them to eat right, I tell them to stay active. We do this together. I tell them this is because we do not want to be permanently ill in the future.
I know my family, not only my kids. I know which diseases my father and mother have had, and their fathers and mothers too. I tell my kids to do things that will minimize the risk for similar ailments in the future. I try and minimize risk myself too, because that benefits me as well as my children.
When they grow up and can make informed medical decisions, I will tell them that they are free to scan their genetic sequence if they choose to.
I do not however, need a genetic scan to see what is good for them and what is not. I know them.
If you do not know your kids, – please start getting to know them now. To do that you do not need genetic testing, you need attentiveness and presence.
With this post, my posts on genetic counseling are now a trilogy (which somewhat unfairly puts them in the same category as some amazing literature, – and films).
From a recent Nature News Special Report:
No one denies that genetic test results can be life-altering for some individuals. But research by Theresa Marteau, a health psychologist at King’s College London, and others has shown that most people are remarkably resilient in the face of traumatic genetic test results. They typically report feeling anxious or depressed around the time of testing, but these effects dwindle within a few months.
This fits well with my first post where I argued that the need for genetic counselors was overrated. After reading an article on Huntington’s disease however, I changed my mind, and wrote another blog post. But now, this quote contradicts what I thought was my final conclusions and I am left wondering where I stand … again:
Studies by Aad Tibben, a psychologist and psychotherapist at Leiden University Medical Centre in the Netherlands, and his colleagues showed that people who took predictive tests for Huntington’s disease mostly recovered from the shock. Many actually felt more in control after testing because they could make arrangements for care, or even for euthanasia.
And I am not the only one who is confused on these matters
With so much uncertainty about how people deal with genetic risk, is genetic counselling necessary or helpful for people undergoing the less definitive tests for an increased propensity for heart conditions or diabetes? “I’m convinced it’s necessary,” says Tibben. But he and others in the field acknowledge that there is little in the way of controlled trials to support their belief.
I have decided to go with the conclusion that the best thing to do is probably to do the genetic counseling,… and then evaluate,… and then stop doing it if it doesn’t work. This simply because to my knowledge, genetic counseling doesn’t do any harm. It may even do some good even if the effect is all placebo:
“……….Did the counsellor help the patient understand complicated risks, or just provide some face-to-face contact and empathy in a confusing medical world?
So, until someone comes out with a study that says that genetic counseling is harmful, this post will reflect my final (!?) postition. End of story (trilogy).
After reading “Living at risk: Concealing risk and Preserving Hope“, which was an eye-opening experience, I am ready to argue against myself and the arguments in my previous post “Now why do we need genetic counselors ?”.
In this post I predicted that genetic counselors may soon be obsolete because nobody cares about low-risk alleles. In addition I argued that information on high-risk alleles is better managed by physicians.
The not caring bit is still true (unfortunately) as far as I know, but after reading the above mentioned paper, I need to modify my opinion on high risk tests. High risk tests in this context, are tests that if positive, means developing disease in the near future. Testing for Huntington disease is a model example of such tests since:
“Penetrance, the likelihood of showing symptoms of the disease if the associated genetic mutation is present, is virtually 100%.”
Thus, this is a clear medical case and a physician should be able to give adequate counsel to the patient. But, the issues a practitioner would face are so much more than medicine alone and recommendations for counseling goes wider than what is expected of a primary care physician:
Nearly every participant with children experienced terrible difficulty in talking to their children about their risk, even when the children were grown. We infer from this difficulty that practitioners could, and should, find ways to help people at risk develop plans for educating their children at an appropriate age. We envision such plans to be developmentally based, geared to answering questions at the child’s level, as well as being persistent and gradual in the presentation of the issues of importance.
This to me, sounds like genetic counseling. Further arguments for genetic counseling comes from the recommendations to the clinicians:
Clinicians also need to reflect on their own beliefs and biases about genetic testing, and to examine the extent to which those beliefs and biases present themselves in their care for people at risk for HD. Primary care health professionals need to be cognizant of the fact that just because a test can be done does not mean that it should be done. What these men and women are telling us is that it is not safe to assume that genetic testing for incurable diseases will necessarily provide information that is wanted, or needed, by those at risk and that testing may have a significant negative impact on the lives of their patients.
Objectively reflecting on genetic testing as well as telling the patient that it may actually be wise not to get tested, are probably things a genetic counselor would do better than the primary care physician.
So, the conclusion must be: I was wrong, we need genetic counselors. Reading “Living at risk: Concealing risk and Preserving Hope” will tell you this. In adition it will teach you that 80-85 % of at risk individuals elects not to undertake predictive genetic testing. They do so to survive since a lack of hope can be devastating:
Something that my uncle said, that I think really stuck with me, is he wrote a suicide note. He said that there’s such a big difference between living with hope and living with knowledge. And that he would take the living with hope any day. And so he really did not think we needed to know, one way or another.
…………and, proper counseling (not only genetic) may be a help for people in handling their life at risk since:
It is noteworthy that several participants said the interview for this study was their first opportunity to talk about the emotional side of HD, despite their years of experience with neurological, cognitive, and psychomotor testing …………… We think that unstructured interviews might actually change the views and actions of the participants with respect to their careful concealment of risk and their preservation of hope.
This is probably true. Regardless of the extent of counseling, it seems to me that genetic counseling for these patients and their family members is a good starting point.
The final take home message must be that not testing for a condition has significant value, especially when treatment options are scarce or non-existent.
Hope is sometimes a life saver. Knowledge on the other hand, can put peoples lives in ruins. Use this as a guiding light if you will, – I know I am going to.