The Pitfalls Of Breeding With The Older Generation

[asal]

saw this today.

real food for thought in light of the push to wait for your dogs to age before breeding from to help eliminate genetic faults.

its already known that the mothers aging eggs in older mothers is a direct cause of higher percentage of downs syndrome and goodness knows how many other forms of damaged dna that then becomes inheritable in the offspring.

at least human parents cant be sued (yet?)

breeders certainly are held accountable

seems we just cant win

http://www.nature.co...hey-age-1.11247

Nature | News

Fathers bequeath more mutations as they age

Genome study may explain links between paternal age and conditions such as autism.

Ewen Callaway

22 August 2012

In the 1930s, the pioneering geneticist J. B. S. Haldane noticed a peculiar inheritance pattern in families with long histories of haemophilia. The faulty mutation responsible for the blood-clotting disorder tended to arise on the X chromosomes that fathers passed to their daughters, rather than on those that mothers passed down. Haldane subsequently proposed1 that children inherit more mutations from their fathers than their mothers, although he acknowledged that “it is difficult to see how this could be proved or disproved for many years to come”.

That year has finally arrived: whole-genome sequencing of dozens of Icelandic families has at last provided the evidence that eluded Haldane. More­over, a study published in Nature finds that the age at which a father sires children determines how many mutations those offspring inherit2. By starting families in their thirties, forties and beyond, men could be increasing the chances that their children will develop autism, schizophrenia and other diseases often linked to new mutations. “The older we are as fathers, the more likely we will pass on our mutations,” says lead author Kári Stefánsson, chief executive of deCODE Genetics in Reykjavik. “The more mutations we pass on, the more likely that one of them is going to be deleterious.”

Haldane, working years before the structure of DNA was determined, was also correct about why fathers pass on more mutations. Sperm is continually being generated by dividing precursor cells, which acquire new mutations with each division. By contrast, women are born with their lifelong complement of egg cells.

Stefánsson, whose company maintains genetic information on most Icelanders, compared the whole-genome sequences of 78 trios of a mother, father and child. The team searched for mutations in the child that were not present in either parent and that must therefore have arisen spontaneously in the egg, sperm or embryo. The paper reports the largest such study of nuclear families so far.

Fathers passed on nearly four times as many new mutations as mothers: on average, 55 versus 14. The father’s age also accounted for nearly all of the variation in the number of new mutations in a child’s genome, with the number of new mutations being passed on rising exponentially with paternal age. A 36-year-old will pass on twice as many mutations to his child as a man of 20, and a 70-year-old eight times as many, Stefánsson’s team estimates.

The researchers estimate that an Icelandic child born in 2011 will harbour 70 new mutations, compared with 60 for a child born in 1980; the average age of fatherhood rose from 28 to 33 over that time.

Most such mutations are harmless, but Stefánsson’s team identified some that studies have linked to conditions such as autism and schizophrenia. The study does not prove that older fathers are more likely than younger ones to pass on disease-associated or other deleterious genes, but that is the strong implication, Stefánsson and other geneticists say.

Previous studies have shown that a child’s risk of being diagnosed with autism increases with the father’s age. And a trio of papers3–5 published this year identified dozens of new mutations implicated in autism and found that the mutations were four times more likely to originate on the father’s side than the mother’s.

The results might help to explain the apparent rise in autism spectrum disorder: this year, the US Centers for Disease Control and Prevention in Atlanta, Georgia, reported that one in every 88 American children has now been diagnosed with autism spectrum disorder, a 78% increase since 2007. Better and more inclusive autism diagnoses explain some of this increase, but new mutations are probably also a factor, says Daniel Geschwind, a neuro­biologist at the University of California, Los Angeles. “I think we will find, in places where there are really old dads, higher prevalence of autism.”

However, Mark Daly, a geneticist at Massachusetts General Hospital in Boston who studies autism, says that increasing paternal age is unlikely to account for all of the rise in autism prevalence. He notes that autism is highly heritable, but that most cases are not caused by a single new mutation — so there must be predisposing factors that are inherited from parents but are distinct from the new mutations occurring in sperm.

Historical evidence suggests that older fathers are unlikely to augur a genetic meltdown. Throughout the seventeenth and eighteenth centuries, Icelandic men fathered children at much higher ages than they do today, averaging between 34 and 38. More­over, genetic mutations are the basis for natural selection, Stefánsson points out. “You could argue what is bad for the next generation is good for the future of our species,” he says.

[sandgrubber]

If I understand the mechanisms, the amount of DNA damage per year should be more or less the same for all species. This means your 10 year old dog is equivalent to a 10 year old boy. So I wouldn't worry about it. At least your old guys give you info about how well the line ages . . . and greater protection diseases like epilepsy often show up at five or six years.

[asal]

If I understand the mechanisms, the amount of DNA damage per year should be more or less the same for all species. This means your 10 year old dog is equivalent to a 10 year old boy. So I wouldn't worry about it. At least your old guys give you info about how well the line ages . . . and greater protection diseases like epilepsy often show up at five or six years.

From all the litrature I have read a 10 year old dog is the equivalent of a 53 year old human.

a 5 year old dog is equivalent to a 33 year old. I know doctors prefer to check women that age and over for downes. As they have found the risk can significantly higher than that of younger mothers.

until I noticed that research I had no idea the problem was also in the male as well. hence my posting it.

http://www.onlineconversion.com/dogyears.htm

"Note: It is a common belief that 1 human year is equal to 7 dog years. That is not very accurate, since dogs reach adulthood within the first couple of years. The formula used above is from a canine expert and is a bit more accurate. (as accurate as one can judge these things)

The formula is: 10.5 dog years per human year for the first 2 years, then 4 dog years per human year for each year after."

I am not against using the older dog as the idea certainly has merit, but learning that means besides the genes they do have age can add some changes that were not there. Yet being the breeder if this does happen the blame lands on you even though you had done your best to ensure soundness was in the parents. Very disheartening a new mutation can end up in the mix through no fault of the breeder.

was the reason I posted it.

Puppy buyers are being encouraged to blame the breeder when something is wrong, this mindset is not fair, no one I know anyway wants to breed a puppy with problems, genes do as they please and always have. As any genetist can tell you, mother natures likes change.

[asal]

as for autism, how many have seen the reasearch that autism may be caused by toxic bacteria in the gut of the affected?

very interesting research, forget the name of the bacteria but apparently is incredibly difficult to remove once it has infected the intestines of the victum.

[asal]

http://microbialinfluence.com/ASD.html

Gut Microorganisms and Autism: the Latest Research

We have collected many research articles to show that the toxins found in microorganisms play an important role in the suspected causes of ASD, in particular, lipopolysaccharide ( LPS) the bacterial toxins from gram negative bacteria that inhabit the guts of autistic children. LPS toxicity works synergistically with mercury and other heavy metal poisonings to expand damage. These heavy metals increase harm from LPS.[1] In addition, LPS decreases glutathione levels making it even more difficult for the body to detoxify heavy metals.[2]

One explanation for why symptoms of mercury are so similar to the symptoms of LPS could be the fact that mercury inhibits carbohydrate absorption in the gut. Unabsorbed food does not get into the blood stream quickly; when it remains in the gut, it becomes available as a food supply for bacteria. Consequently, gram negative bacteria multiply and produce LPS. [3] This raises a strong suspicion that some of the symptoms commonly attributed to mercury could be directly caused by LPS and only indirectly by mercury.

LPS also renders toxins from Candida Albicans more damaging.[4] The poisonous effects of LPS are so potent that they produce symptoms of autism even without the help of Candida Albicans and heavy metals. All collected experiments on the following website involve laboratory mice injected with only LPS and exhibiting the same symptoms as those in ASD.

LPS induces a depressive syndrome, characterized by anhedonia, anorexia, body weight loss, and reduced locomotor, exploratory, and social behavior. This result has been replicated so many times by different research studies that the names, "Sickness Behavior" and "Endotoxemia" are now applied to this condition. [5][6][7]

The mission of this website is to collect and display links to some of the available research articles from PubMed, a service from the National Library of Medicine and the National Institute of Health, that link LPS to the varied and diverse symptoms of ASD. We were able to find and collect experiments for almost every possible neurological and biological symptom of ASD in order to prove that most symptoms of ASD, have a corresponding experiment on Medline that proves each is a symptom of LPS toxicity.

The articles on this website are just a tiny fraction of the available research The amount of evidence is overwhelmoing, for example, performing a search for "hippocampus lps", in PubMed will retrieve 222 citations.

The number of similarities between ASD and LPS toxicity is sufficiently impressive to demand attention and cannot be ignored. The following are symptoms of LPS poisoning; these symptoms are also found in children with autism:

BRAIN

Reductions in oligodendrocyte or myelin markers

A marked cerebral cytokine response

White matter injury

Changes in amygdala

Change in dopamine and serotonin levels

Reduction of blood flow to the brain

Changes in blood-brain barrier permeability for large (protein) molecules

Increased the number of pyramidal and granular cells in the hippo-campus

EMOTIONS AND BEHAVIOR

Anxiety

Depression

Reduction in social behavior

Lack of social interaction

Increase in addiction

Lack of exploratory behavior

DIGESTIVE

Weight loss

Breakage and depletion of microvilli

The tight junctions widen and become disrupted.

IBS and IBD

Gut inflamation

Leaky Gut

Digestive symptoms

Disrupted Intestinal Transit

LPS is linked to the problems of gluten,soy and dairy in ASD children

IMMUNE FUNCTION

Increase in TNF alpha.

Increases in certain NK cells and monocytes

Increases in lymphocytes

OTHER

Low Levels of Thyroid

Low Levels of Glutathione

Low Levels of Amino Acids

Impairment of Bile Flow

Increasing the Number of Viable Candida Albicans

An increase in pain sensitivity

Researchers at the UC Davis M.I.N.D. Institute found clear differences in cellular responses between autistic children and neurotypical children following exposure to LPS, bean lectin and bacterial agents. At the Institute this was discovered to be a major and important difference between children with ASD and typical children.[8]

Many in the ASD community blame mercury in vaccines for causing autism. Note that the vaccines contain LPS or other toxins from microorganisms. It is possible that LPS and other microbial toxins also play a key role in the vaccine damage.

"Lipopolysaccharide (LPS) is localized at the exterior leaflet of the outer membrane and serves as the major surface component of the bacterial cell envelope. This remarkable glycolipid is essential to virtually all Gram-negative organisms and represents one of the conserved microbial structures responsible for activation of the innate immune system. For these reasons, the structure, function, and biosynthesis of LPS has been an area of intense research."[9]

The majority of the research articles involve mice or humans displaying symptoms of toxemia after being given an injection of LPS. Another method to assess the important influence of bacterial toxins is to observe the changes in ASD children after removal of the neurotoxin-producing bacteria. Both Vancomycin and the Specific Carbohydrate Diet (SCD) are treatments for removal of bacteria. Both treatments produce a decrease in the symptoms of ASD. However, the changes from vancomycin were only short term because the bacteria develop a resistance to the medication. Changes from SCD diet are more powerful because they are long lasting. Even adults with ASD who live in group homes have been shown to lose many of their symptoms after being on the diet. SCD now also eliminates beans during the early months of the diet and encourages parents to only use beans later provided there are no adverse reactions.

UC Davis M.I.N.D. Institute reports in its findings concerning the reaction of autistic children to LPS, bacterial agents and lectin from beans "may lead to significant advances in the early detection, prevention and treatment of this complex neurological disorder."[8]

We are in total agreement, and offer as our own evidence, scientific articles and many positive results from using a diet that eliminates neurotoxin-producing bacteria and fosters intestinal healing.

In view of the research, we have to consider Lipopolysaccharide (LPS) a poison, as toxic as mercury and other heavy metals, LPS has drastic consequences for those in the ASD Community. Fortunately, dramatic improvements may result after its removal.

Increasing awareness of LPS to doctors, researchers and parents, will hopefully result in an increase in recovery rates for autism.

The links on the upper side of this website provide comprehensive research about LPS from around the world.

[1] Rumbeiha WK, Fitzgerald SD, Braselton WE, Roth RA, Kaneene JB: Potentiation of mercury-induced nephrotoxicity by endotoxin in the Sprague-Dawley rat. Toxicology. 2000 Aug 21;149(2-3):75-87.

[2] Zhu Y, Carvey PM, Ling Z : Altered glutathione homeostasis in animals prenatally exposed to lipopolysaccharide. Neurochem Int. 2007 Mar;50(4):671-80. Epub 2007 Jan 13.

[3] Read the articles in the "Treatments for LPS" section of this website

[4] Akagawa G, Abe S, Yamaguchi H. Mortality of Candida albicans-infected mice is facilitated by superinfection of Escherichia coli or administration of its lipopolysaccharide. J Infect Dis. 1995 Jun;171(6):1539-44.

[5] Singal A, Tirkey N, Pilkhwal S, Chopra K. Green tea (Camellia sinensis) extract ameliorates endotoxin induced sickness behavior and liver damage in rats. Phytother Res. 2006 Feb;20(2):125-9.

[6]R. YIRMIYA, Y. POLLAK, M. MORAG, A. REICHENBERG, O. BARAK, R. AVITSUR, Y. SHAVIT, H. OVADIA, J. WEIDENFELD, A. MORAG, M. E. NEWMAN, T. POLLM�CHER (2000) Illness, Cytokines, and Depression Annals of the New York Academy of Sciences 917 (1), 478�487.

[7]Marvel FA, Chen CC, Badr N, Gaykema RP, Goehler LE: Reversible inactivation of the dorsal vagal complex blocks lipopolysaccharide-induced social withdrawal and c-Fos expression in central autonomic nuclei. Brain Behav Immun. 2004 Mar;18(2):123-34.

[8] Link to the anouncement from the M.I.N.D. Institute.

[9] Trent, M. Stephen1; Stead, Christopher M.1; Tran, An X.1; Hankins, Jessica V.(2006). Diversity of endotoxin and its impact on pathogenesis. Journal of Endotoxin Research, Volume 12, Number 4, August 2006, pp. 205-223(19)

[10]Autism: Effective Biomedical Treatments (Have We Done Everything We Can For This Child? Individuality In An Epidemic) by Rimland, Ph.D. Bernard (Introduction), M.D. Sidney Baker (Author), Ph.D. Jon Pangborn (Author) Boston DAN! April 2005 edition. Page 24

Edited September 9, 2012 by asal

[asal]

expect many are wondering what the?

well 20 years ago the mothers were told their flawed raising of their child had caused autism.

now we have camps that believe its genetic.

camps that have discovered overwhelm the "bacterial toxins from gram negative bacteria that inhabit the guts of autistic children." and definate return to normal in the child has occured if done soon enough although the bacteria are so immune to distruction no way has been found yet to remove them permantly once they have colonised.

scarey stuff.

if medicine has so far to go on so many levels. its weird surely if a pup has a similar problem is automatically the breeders fault no matter what it may be.

demonising breeders is not going to encourage anyone to stay a breeder for too long especially the ones who really care about doing their best.

Maybe a better heading is the pitfalls of breeding at all :laugh:

Edited September 10, 2012 by asal

[sandgrubber]

If I understand the mechanisms, the amount of DNA damage per year should be more or less the same for all species. This means your 10 year old dog is equivalent to a 10 year old boy. So I wouldn't worry about it. At least your old guys give you info about how well the line ages . . . and greater protection diseases like epilepsy often show up at five or six years.

From all the litrature I have read a 10 year old dog is the equivalent of a 53 year old human.

....

That is roughly true when you're speaking about organs (including bones, skin, etc.), but cell mutation is different. At the cell level, it is thought that the probability of mutation of a specific gene is roughly constant per year. That is to say, a year in a dog's testes is the same as a year in a man's testes, and the probability of things going haywire is cumulative over time. Dogs, being shorter-lived, don't have as much time for mutations to accumulate. See, Mutation rates in mammalian genomes, S. Kumar, S. Subramanian, Proc. of the NAS 99, 803–808. 2002.

My statement may be off, as presumably inherited mutations occur in the reproductive organs. Thus it might be more accurate to start the count from the age of sexual maturity . . . making a 10 year old dog (assume viable sperm created at 1 yr) somewhat equivalent to a 23 year old human (assuming viable sperm produced at 14).

Science isn't good at establishing mutation rates. They vary for different alleles and different species, and are affected by environmental factors. But as far as I know, the concept that chance of mutation is more or less constant over time has not been seriously contested. . . . and all else equal, more years, means more mutations. Ie, longer lived animals are more likely to suffer from mutations occurring in cells of the reproductive organs.

Bottom line: given a choice, I will always prefer an older dog.

p.s. I have taken concepts used to try and translate measurements of genetic divergence between lineages to geologic time and used them on time scales of a few generations. There may be reasons that this shouldn't be done. I'm outside my field of expertise. Happy to be corrected.

Edited September 11, 2012 by sandgrubber