De Novo Mutations and Autism
By Teresa Conrick
It's been all over the news and it really is NOT NEW news. The idea of paternal age and these "de novo mutations" has been one of the many exaggerated "THE reason" studies for Autism over the years. Many think it is a wasteful approach to exploring Autism's causation as it does little in stopping the rising epidemic numbers and nothing for those affected by a constellation of extreme health issues and behavioral symptoms.
Here on Age of Autism, Bob Krakow recently wrote a thoughtful article about this topic :
"...this paper may really show is that there exists a double role for environmental factors, as follows: (1) environmental factors cause de novo mutations, as reflected in the paper's data, and the mutations accumulate with age, (2) the de novo mutations create vulnerability in some children, and (3) environmental factors then trigger disease in the (environmentally-caused) genetically susceptible children. Thus, rather than showing that autism or schizophrenia may be primarily genetic, the paper supports the argument that the significant operative variables are environmental."
Examining examples then of environmental factors causing these de novo mutations seems to be a good idea. Allowing one more study to tell us the same wrongly focused scenario over and over is an expensive and inappropriate use of funding for Autism research.
The following samples of research show us a picture of what can be happening:
- De Novo Mutations:"Not inherited. A genetic difference that is not inherited but arises due to a gene alteration that appears in one family member as a result of a mutation in an egg or a sperm of one of the parents, or in the fertilized egg itself. The mutation is not part of the parent's overall genetic code."
- MUTAGEN: "An agent, such as a chemical, ultraviolet light, or a radioactive element, that can induce or increase the frequency of mutation in an organism."
Fluzone vaccine nor Influenza A (H1N1) 2009 Monovalent Vaccine have been
evaluated for carcinogenic or mutagenic potential, or for impairment of
- "... thimerosal is genotoxic" - Genotoxic: Damaging to DNA and thereby capable of causing mutations or cancer.
- Thimerosal is a widely used preservative in health care products, especially in vaccines. Due to possible adverse health effects, investigations on its metabolism and toxicity are urgently needed....Thus, genotoxic effects were seen even at concentrations which can occur at the injection site. Toxicity and toxicity-related elevation of micronuclei was seen at and above 0.6 micro g/ml thimerosal......These data raise some concern on the widespread use of thimerosal.
In 2010, after yet another "Old dads cause autism" study hit the news, a twist from blaming the mother in Autism, this paper was published to examine how paternal de novo mutations could be risk factors in Autism:
2010 JanEnvironmental risk factors for autism: do they help cause de novo genetic mutations that contribute to the disorder? Abstract
"Recent research has discovered that a number of genetic risk factors for autism are de novo mutations. Advanced parental age at the time of conception is associated with increased risk for both autism and de novo mutations. We investigated the hypothesis that other environmental factors associated with increased risk for autism might also be mutagenic and contribute to autism by causing de novo mutations. A survey of the research literature identified 9 environmental factors for which increased pre-conceptual exposure appears to be associated with increased risk for autism. Five of these factors--mercury, cadmium, nickel, trichloroethylene, and vinyl chloride--are established mutagens. Another four--including residence in regions that are urbanized, located at higher latitudes, or experience high levels of precipitation--are associated with decreased sun exposure and increased risk for vitamin D deficiency. Vitamin D plays important roles in repairing DNA damage and protecting against oxidative stress--a key cause of DNA damage. Factors associated with vitamin D deficiency will thus contribute to higher mutation rates and impaired repair of DNA. We note how de novo mutations may also help explain why the concordance rate for autism is so markedly higher in monozygotic than dizygotic twins. De novo mutations may also explain in part why the prevalence of autism is so remarkably high, given the evidence for a strong role of genetic factors and the low fertility of individuals with autism--and resultant selection pressure against autism susceptibility genes. These several lines of evidence provide support for the hypothesis, and warrant new research approaches--which we suggest--to address limitations in existing studies. The hypothesis has implications for understanding possible etiologic roles of de novo mutations in autism, and it suggests possible approaches to primary prevention of the disorder, such as addressing widespread vitamin D deficiency and exposure to known mutagens."
Some key pieces in that full paper:
- ...review evidence for mitochondrial as well as nuclear genomic instability in autism,
- ...the lifelong production of sperm cells offers significantly more opportunities for mutations than is the case for ova.
- Palmer et al. found that autism prevalence increased 2.6% for every 1000 lb of mercury released in the vicinity of the geographical center of a given district, and 3.7% with nearby power plant emissions.
- Several lines of evidence indicate that oxidative stress induces mutagenesis
- Sperm cells appear to be more vulnerable to the mutagenic effects of oxidative stress than oocytes. Several features of sperm cells, including the unique membrane structure crucial to fertilization, provide greater opportunities for the production of ROS
- ...rat liver cells treated with vitamin D four weeks before the introduction of a mutagenic agent showed significantly fewer chromosomal aberrations
- The present hypothesis does not exclude a role for gestational and childhood exposure to toxic factors in the etiology of autism, as oxidative stress and mutagenic effects are also likely to have adverse effects on mitosis and development.
Many would like to ONLY research gestational causes as it then gives the flavor that Autism is solely "genetic" when much evidence shows vulnerability before and after birth to be the increasing factor causing the epidemic numbers. The paternal de novo mutation caused by mercury exposure does exemplify the research done by Mark Blaxill and Dan Olmsted in their book, The Age of Autism: Mercury, Medicine, and a Man-Made Epidemic:
"We believe that autism was newly diagnosed in the 1930s for the simple reason that it was new. The organic chemicals industry that grew out of chemical warfare industry research during World War I led to new commercial uses for mercury, including the introduction of some extraordinarily toxic compounds made from ethylmercury. This, our research suggests, led directly to the first cases of autism......families cluster around the medical profession, agriculture, and forestry---the three biggest risk factors for exposure to mercury in its newest and most toxic form.....Elizabeth Peabody Trevett's work with the well-baby clinic and its diphtheria vaccination component at Harvard is the most direct sign of a connection to heightened risk of infant vaccination with a thimerosal- containing vaccine in the first cases....The way some of the early cases clustered around Baltimore and its active anti-diphtheria campaign starting in the early 1930s is also noteworthy."
Very noteworthy yet the fear of this truth has many scrambling to deny
it. Why is that? Maybe because there is an entire industry of
billions of dollars tied up to vaccination as well as rising issues of
pollution, agricultural pesticides and toxic food additives. Since the
1930s, fierce toxic, industrial growth has become very possibly the fuse to
Autism but excessive vaccination is the flame exploding in every state, county
and small town. We all need to demand research and treatments that will
stop this epidemic and help those affected today. Our children and our
descendants are so worth this effort.
Teresa Conrick is Contributing Editor for Age of Autism.
I understand and your questions were good ones. They were all excited when I was very young about the idea of curing genetic diseases think of the possiblity of taking viruses and making them deliver the right DNA to all the cells.
Actually it is Frankenstein stuff now that I think about it.
But their study of older fathers as you pointed out - and so you very well know -- you and I are not part of those stats; there are a lot of young fathers in all this too.
The study will not hold up; will not be able to be duplicated. As you and I well know too.
Posted by: Benedetta | August 29, 2012 at 09:16 PM
Benedetta I don't believe it for a minute, it's not my experience or the experience of anyone I know. I am very curious as to these de novo genes, and "so " want it to understand what they are, how they can arise , the timing of life that this can happen. I remember the blood brain barrier issue in a similar way, we were all told it closed by birth, now some are saying two, some are saying 6 months, others 22 days after birth.(mentioned timing in studies) I've heard , as well that children with neurological problems may never achieve closure of the blood brain barrier. Many of us have our ASD child's first experience with thimerosal and hepatitis b on the day they were born. Preemies and c-section kids are said to be more at risk of autism, these kids are born earlier , mine would be included in this group, but my sister's child was born almost 8 lbs on time. The fathers I know while not teens, were in their twenties with the oldest being 31, my hubby was 38 when my healthy son was born! This elderly father business is clearly funded by pharm for a distraction.
Natasa has a handle on the de novo current info, I have a list of questions bordering on nuts, remembering the old tests of chemicals tested on viruses such as varicella to determine mutation ability, I'm pretty much in the dark ages. We now know of the retroviruses and their potential to incorporate themselves into our dna, and of epigenetic forces influencing replication and signaling, I don't understand any of it. Adding into this mix is the vaccine programs injecting dna of porkine viruses ( I believe they are known mutagens) human dna, mixing with chemicals known to be teratogens ,mutagens, etc.. I wish it was more clear cut, that studies have proven something, but in looking, it seems our kids are victims of a huge lack of knowledge and a lack of safety studies in a very dangerous vaccine program.
Posted by: barbara j | August 29, 2012 at 06:24 PM
Many here are assuming that the findings that older fathers have kids with autism is correct. Then many are making a good assumption that it is because of environmental insults that caused that.
I however, don't even believe the stats or study that says it is older fathers. They have either messed it up (on purpose) or (stupidity) by picking the wrong population to study.
Posted by: Benedetta | August 29, 2012 at 02:35 PM
vitamin D is intimately involved in DNA repair and thus point mutations, even double stranded break repair.
Posted by: John Cannell, MD | August 29, 2012 at 02:13 PM
Thank you Natasa! This is all so very difficult to understand for me.
Posted by: barbaraj | August 29, 2012 at 11:47 AM
PS to go back to your question barbara, yes these retroactive fragments are not only often 'functional' (in the sense that they can insert into host DNA and influence their expression, or possibly lead to mutations) but scarier still these 'fragments' are often highly capable of recombining with other viral and host elements to form more functional/active/sneaky pathogens. Science is only beginning to scratch the surface of these phenomena.
Posted by: Natasa | August 29, 2012 at 09:45 AM
Good question barbaraj, it could be both - ie that these mutations are just another 'byproduct' of whatever causes autism (ie non-contributing to pathology).
Active exogenous retroelements (and following these, reactivated endogenous ones) will not only carry the risk of mutagenesis but will also heavily influence expression levels of nearby 'healthy' genes to suit its long and short term purposes.
Posted by: Natasa | August 29, 2012 at 09:40 AM
Still scratching my head. Agree with Natasa ! Does anyone know if these genes are functional or if they are just an interesting artifact? I would "think" the introduction of foreign dna into vaccines, that of both human and animal "could" along with a chemical soup mixed with viral and bacterial components cause fragments , simple fragments to circulate, but are they functional..do they really play a part in any disease process or any process at all. We know vaccines cause autism, we don't know if these de novo genes do anything at all. Certainly foreign dna could be suspect , could this relate in some way to a rejection process?
Posted by: barbaraj | August 29, 2012 at 09:19 AM
A little off topic but I stumbled across this last week when doing my own research after reading this study.
children inherit the mother's mitochondrial
my favorite reference on diet and dna
and it makes perfect sense that a toxic load of vaccines would do the same
Posted by: Diane W Farr | August 29, 2012 at 09:11 AM
The heavy rain areas are going to have higher levels of mercury pollution as well. Since 1997 they have been measuring the amounts of mercury in the rain in PA http://www.dep.state.pa.us/dep/deputate/airwaste/aq/acidrain/acidrain.htm .
With heavy rain areas I always think of toxic mold as being a contributing factor to ill health as well and of course viruses play an important role in mutations.
These factors may contribute to ill health, but vaccines are the causal agent.
Posted by: Patrick | August 29, 2012 at 07:33 AM
The continuation of governmental policies by the elected representatives makes sure the golden vaccine cow is protected...We need a Murdoch situation (as in the UK) where he and his journo shilss corrupted the Police and the structure of the Uk and it came back to bite them...go to jail ..go directly to jail..do not pass go..all pharma shills..
Posted by: Angus Files | August 29, 2012 at 07:25 AM
Contamination of vaccines and biological products by retroelements (from cell lines etc) would be a prime DNA mutagenic suspect.
Posted by: Natasa | August 29, 2012 at 06:26 AM