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Jet&Copper
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07-10-2012, 08:46 AM
Originally Posted by rune View Post
There is quite a lot of publicity surrounding cousin marriages in some areas and the effect it is having on the numbers of children with various syndromes, some of which are quite rare. There was a radio 4 programme about it quite recently.

rune
Absolutely. There is absolutely no denying that inbreeding leads to a massive increase in the risk of developing genetic defects. That anyone would claim otherwise is disturbing - it seems to be rather unique to the dog world this one!

Lots of human populations are already rather inbred, when compared to the general population, and each of these individual populations have their own unique list of genetic problems that are well documented.

Again of course you can be perfectly outbred and still suffer from a genetic problem - however the risk of this problem running through your entire line is very small, if you look at my previous example we go from a recessive germline mutation effecting 1 in 10,000 individuals in an outbred pop, the numbers dive to 1 in 4 in just a few generations in an inbred pop.

We havent even covered dominance, penetration and accumulative effects!

Im tryin to think of a basic analogy to describe my long posts.
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07-10-2012, 09:31 AM
Actually a good example of the human problem is the haemophilia in the royal families.

rune
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Jet&Copper
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07-10-2012, 09:55 AM
Originally Posted by rune View Post
Actually a good example of the human problem is the haemophilia in the royal families.

rune
Indeed. A good analogy for the breeding world as we have detailed pedigrees for the royal family going back centuries. We can even see which individual the mutation arose in and then watch is spread through the lines

Another good example is a mutation that causes sickle cell anemia - rare is white populations but comparitevely common in African and to a lesser extent certain Asian populations.

This gives a few good genetic terms a real life example. Why is this mutation so prevalent in one pop when compared to another? Just like we asked why is cancer prevalent in certain lines or breeds of dogs but not others, even if both breeds are inbred to a similar degree

First we have "founder effect" - in a closed pop the original founder individuals will have a finite set of genes that they will pass on to their offspring. The genetic fitness of a pop. is extremely dependent on these founder individuals, if that pop remains "closed" ie inbred.

Founder effect will be a real issue in dog breeding as we tend to have populations remain closed. The genetic fitness of the founder animals may not become apperently for many, many generations, due to accumulative effects of deleterious recessive alleles that I described earlier. That's why, I always point out that health testing in dogs is not the be all and end of testing breeding worth - a sire can be carrying a literal truck load of problems that we cannot see,cannot test for and will not necassarily become apparent until many generations later.

Of course we can minimise founder effect - by outcrossing.

Second we have linkage again.
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Jet&Copper
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07-10-2012, 10:01 AM
Sorry stupid phone posted reply before I was finished

Slight oversimplification here, but basically the gene responsible for causing sickle cell anemia sits very close to a gene that confers resistance to malaria. So, individuals that survive malaria in very high risk areas pass on their genes, while those who don't have the mutation, die.

Because the two genes are linked, they are passed on together during sexual reproduction even tho their functions have nothing to do with each other

Can you see how this happens in dog breeding? Genes that are selected for by breeders then "carry forward" other genes that are in no way connected - we could be selecting for certain breeds to be genetically susceptible to cancer without knowing it by deliberately breeding for other traits
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07-10-2012, 10:30 AM
I'm just going to add, in the interests of keeping this as a decent discussion on genetics, that I have already previously and categorically stated that there is no way you can make a legit comparison between which is healthier, a cross breed or a pedigree.

There are simply too many possible variables to consider, in both an individual dogs inherited genetics and the environment it is exposed to throughout it's lifetime.

This is therefore NOT pedigree bashing. In all my previous posts, I am very specifically talking about the effects of inbreeding on a population - a very well studied and very real issue, in many fields not just dog breeding.

There is of course many other aspects of genetics we can talk about that are not necassarily related to inbreeding - SB already touched on one, Epigenetics, there are many more.

Of course crossbreeding, whilst increasing heterozygosity in a closed population, also comes with it's own issues, which we are all free to discuss as well.
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bijou
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07-10-2012, 01:39 PM
Another good example is a mutation that causes sickle cell anemia - rare is white populations but comparitevely common in African and to a lesser extent certain Asian populations.
but would outcrossing in this case not simply spread the sickle cell gene eventually across all races ?
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Azz
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07-10-2012, 02:35 PM
Originally Posted by Fudgeley View Post
I am debating with someone at the moment as to whether pedigree dogs are generally healthier than crossbreeds/mongrels.It is the age old debate of hybrid vigour versus over breeding.
What are your thoughts and is there any actual evidence out there to support either argument?
It's a toughie, and I guess it depends greatly on the gene pool of the breeds being crossed (the less related they are, the healthier you might expect the offspring to be). However if you were on about mongrels and in relation to progeny and the survival of the fittest then the picture would be much clearer, and I doubt any would disagree, and say yes.

Having said that, if you look at the chart Ben M posted, you can see crossbreeds live longer, and although they are 3rd on the chart you have to account for a proportion of those that are giant breeds, who don't usually live as long which will bring them down in the chart... so I would look at the interquartile range for a better indication, which is higher on both counts for any of the large dogs (min), and any of the small (max). So it certainly suggests crossbreeds live longer.

With regards to genes, all offspring inherit them from their parents - and nature's failsafe is if one of the parents has a faulty gene, it will take the gene from the other parent (who hopefully has a perfectly fine gene). However, if both parents are related - then the chance of both of them having the same faulty gene increases - as they are from the same 'stock', which means nature has no choice but to pass that onto the offspring. That's why close-relative matings are a bad idea.

Then you have to look at epigenetics - which the environmental effect on genes. Here I think the effect or cause of certain diseases (and I might guess most that haven't already shown up by puberty) are down to epigenetics, such as cancer, arthritis, heart disease (unless in very old age or towards the end of a dogs natural life). The biggest epigenetic influence in my opinion - is food (or more specifically, bad food).
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Jet&Copper
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07-10-2012, 02:51 PM
Originally Posted by bijou View Post
but would outcrossing in this case not simply spread the sickle cell gene eventually across all races ?
Apologies, I didn't go into enough detail to describe what's actually happening in this example, was trying to keep things as simple as possible.

The sickle cell mutation is only advantageous when inherited in the heterozygous state - one copy is the healthy version, the other copy is the mutated version. This is known as heterozygote advantage, having both the healthy gene and the mutated gene is better than having two healthy genes (as you will have no immunity to malaria) and two mutated genes (you will be too ill with anemia for survival)

The sickle cell mutation is autosomal recessive (incompletely however) - this means that the healthy version is able to "mask" some of it's effects.

Therefore, if you outcross to the general population, you will see the dominant "healthy" gene take over in the original population and we begin to lose the mutation in terms of frequency - as long as the heterozygote advantage is not required for survival, which it isn't in the modern world, and we see this happening - African Americans have a far lower incidence of this mutation than their African counterparts.

(There is more to how this works but wanted to make as much sense as I could).
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Jet&Copper
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07-10-2012, 02:55 PM
Originally Posted by Azz View Post
Then you have to look at epigenetics - which the environmental effect on genes. Here I think the effect or cause of certain diseases (and I might guess most that haven't already shown up by puberty) are down to epigenetics, such as cancer, arthritis, heart disease (unless in very old age or towards the end of a dogs natural life). The biggest epigenetic influence in my opinion - is food (or more specifically, bad food).
Hmmmm where are you getting the information that most diseases that haven't shown up by puberty are down to epigenetic factors?

I'm afraid the vast majority of epigenetic control is conferred in the womb, before birth.

Epigenetics does not change the individual's actual genes, in any way whatsoever.

Can you expand on "bad food?" How does the food we eat, after fetal development, have the ability to change our DNA's methylation status, or histone modifcations? That's not something I've came across, and this is a field I'm heavily involved in
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07-10-2012, 03:39 PM
Originally Posted by Jet&Copper View Post
Hmmmm where are you getting the information that most diseases that haven't shown up by puberty are down to epigenetic factors?

I'm afraid the vast majority of epigenetic control is conferred in the womb, before birth.

Epigenetics does not change the individual's actual genes, in any way whatsoever.

Can you expand on "bad food?" How does the food we eat, after fetal development, have the ability to change our DNA's methylation status, or histone modifcations? That's not something I've came across, and this is a field I'm heavily involved in
If you look at what I said - I said 'I think' and 'I guess' - it was not asserted as fact, and I'm also speaking in a broader sense (epigenetics *and* environmental) though I probably should have made that clearer.

Environmental factors do have an impact on gene related functions of our system - the gene responsible for the production of lactase is a great example. The gene is either in an on state, or off, but in some people it can switch between the two (I am living proof - having had a DNA test to clinically prove this - look up research by Dr Stephanie Matthews and Professor Anthony Campbell).

With regards to food, I'm suggesting that certain diseases such as cancer may not be primarily down to 'bad genes' that we inherit from our parents at birth, but rather, more attributable to environmental factors such as food, exposure to radiation, magnetic fields, toxic substances such as mercury etc. Again, I did not assert this as the final word on the matter (I don't suppose we will know 'for sure' for another few hundred to 1000 years to be honest) but merely my opinion based on personal knowledge and research (specifically of food) over the years - again I stress this is largely environmental, but epigenetic in the sense of how it can have an effect on some genes (such as the lactose example).
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