Some things to be aware of on Arthrogryposis (CCS)

[Mark H]

Some things to keep min mind on CCS or Arthrogryposis:

As previously posted the Charolais and other Continental cattle breeds have displayed calves born with Arthrogryposis.  Some of the early Full French imports in the 1960's displayed this trait.  This led the university of Alberta to establish a carrier herd at their research ranch at Kinsella, Alberta to study this problem and let bull owners show their bulls were "clean".  A couple of interesting things were found in the course of their research.
First, Arthrogryposis displays reduced penetrance when two carriers are mated far fewer than 25% of the calves display the trait that would be expected in classical Mendelian inheritance.  Since the original work was done in the 1970's before DNA sequencing it was verified by mating carriers to carriers.  If this can be verified by DNA sequencing it would be an interesting master's degree thesis for someone.
More on Penetrance: http://en.wikipedia.org/wiki/Penetrance
The second interesting thing that was noticed was that carrier cows were culled far less often than non carriers in the research herd as a whole.  This suggests that the heterozygous state with respect to the normal homozygous stated had a reproductive advantage.  This was borne out by the data collected.  Non carrier cows were far more likely to be culled due to reproductive problems ( not being in calf) than their carrier herd mates.  This has important implications for purebred cattle breeders since empty cows will be culled due to selection for maternal traits.  In short it is likely that the best cows may in fact be carrier cows.  If you use a DNA test to cull out carriers the best maternal females may in fact be eliminated setting the Angus, Charolais, and other breeds maternal performance back by decades.  For more details check out:
 
Goonewardens L.A., Berg R.T., Arthrogryposis in Charolais cattle - a study on gene penetrance, Ann. Génét. Sél. Anim. 8 (1976) 493-499

Linebreeding in this scenario will lead to reduced reproductive performance due to ignoring the heterozygote reproductive advantage.  It would seem that managing the allele so as not to display it while keeping the reproductive advantages of the hetreozygote would be the best course of action.  In short concentrate on reducing the allele's penetrance!

Mark

 

[knabe]

good post mark.  my theory is that i want an avenue of homozygosity that provides another avenue to fertility and not to have to maintain heterozysous state in one's herd.  heterozygotes virtually guarantees a higher cull rate.  by selecting for homozygotes, you naturally create a bottleneck, and by having the advantage that you will have two pools, one with no fertility, and another with fertility, youcan improve with a limited number of generations with fewer animals and cost than higher numbers, and open up the numbers lens when you have traits "fixed".  people seem to have forgotten how or why to do this. 

 

[Mark H]

Knabe,

The problem with trying to get a high degree of  homozygousity with high performance is that no one has been able to get it using high degrees of heterozygousity.  Inbreeding depression impacts the amount of selection pressure you will be able to apply in a finite population.  Inbred cows have fewer calves meaning fewer calves to select from; slowing genetic progress relative to less homozygous lines.  Plants and animals (like chickens) that reproduce at a much greater rate are not as adversely impacted by this.
Also you likely can never achieve a "homozygous" or "pure" line of any animal.  The natural state is for animals to display a large amount of heterozygosity not homozygosity.  Animals that are more heterozygous are more genetically fit-this is where hybrid vigor comes from.  In experiments with flies that were inbred over hundreds of generations in small populations it was expected that many of the genes would become "fixed" or homozygous over many generations in small generations.  This not what they found.  Instead they found a high degree of heterozygousity.  I was reckoned that heterozygosity was needed for survival even in these small population with out a harsh environment to deal with.  Keep in mind from nature point of view heterozygosity is the desired state.  It is easier to work with nature than against it.  If you want to cleanse your herd of lethal recessive alleles via inbreeding you  will be disappointed.  You find more deleterious alleles and reduce animal performance that thew sum of it.

 

[knabe]

Knabe,

The problem with trying to get a high degree of  homozygousity with high performance is that no one has been able to get it using high degrees of heterozygousity.  Inbreeding depression impacts the amount of selection pressure you will be able to apply in a finite population.  Inbred cows have fewer calves meaning fewer calves to select from; slowing genetic progress relative to less homozygous lines.  Plants and animals (like chickens) that reproduce at a much greater rate are not as adversely impacted by this.
Also you likely can never achieve a "homozygous" or "pure" line of any animal.  The natural state is for animals to display a large amount of heterozygosity not homozygosity.  Animals that are more heterozygous are more genetically fit-this is where hybrid vigor comes from.  In experiments with flies that were inbred over hundreds of generations in small populations it was expected that many of the genes would become "fixed" or homozygous over many generations in small generations.  This not what they found.  Instead they found a high degree of heterozygousity.  I was reckoned that heterozygosity was needed for survival even in these small population with out a harsh environment to deal with.  Keep in mind from nature point of view heterozygosity is the desired state.  It is easier to work with nature than against it.  If you want to cleanse your herd of lethal recessive alleles via inbreeding you  will be disappointed.  You find more deleterious alleles and reduce animal performance that thew sum of it.

well, i guess i'm not after "high" performance.  an ls6 '70 chevelle is not my goal.  inbred anything without selecting for fertility is pointless.  i am aware of the reproduction rates.  i am also aware of reproduction rates beyond those, where chromosomal rearrangement is actually required for diversity such as in poplar trees, frogs, sea squirts etc.  the problem with the fly analogy, again, tried many times, including where i worked as a pesticide screener where we had an inbred fly population that had no predation and you could literally pick the flies up and pet them.  one day, my office mate left the screen of his bucket and there was flies and pooh everywhere.  i agree heterozygosity has it's place.  however, many land races were created through bottlenecks which benefitted many a new species, some obviously bad such as cheetahs, though their decline is from human the interval of interraction with germs etc....  one can find this in humans over and over with many genes that populations are homozygous, especially in response to the plague, which by the way offers resistance to aids in 10% of the white population.  keep in mind, the desired state for PHA and TH is the homozygous state.  the working with nature comment is relevant by culling more rigorously. it's pretty clear, that one can inbreed and get rid of PHA and TH.  the key is finding the deleterious alleles rather than keeping them hidden through heterozygosity. performance is relative.  i don't want to run my cows on nitro.

 

[Mark H]

Knabe,

PHA and TH likely had their increase in allele frequency due to founder effect.  Clubby cattle tend to be 2 or three way crosses and if these breeding populations had been established with a wider genetic base it is not likely that either allele would have surfaced and caused so much heartburn.  But perhaps the simple lethal recessive model also does not apply here.  What if the heterozygote for these alleles has a phenotype that gives the clubby look?  Wouldn't heterozygotes for these alleles be given an advantage (albeit an artificial one) in clubby herds?
Heterozygousity does not mean you are going for an ultra high performance, intensive cross breeding system it is useful in extensive range cattle situations where weaning weights never get above 600 Lb all the way to getting European double muscled cattle that cut out at 80% at 15 months old and 1500 LB.  In both cases heterozygosity makes these goals easier to achieve.
Lastly homozygosity is very rarely the preferred state.  It has been shown since the 1960's that heterozygosity is in fact the vastly more common state.  The paper that started it all:

Lewontin, R. C.; J. L. Hubby (1966). "A molecular approach to the study of genic heterozygosity in natural populations. II. Amount of variation and degree of heterozygosity in natural populations of Drosophila pseudoobscura". Genetics 54: 595–609.

This paper started an industry looking into genic polymorphism with citations into the thousands.  It is a pity that Animal Science programs in the United States have not used findings in population genetics in designing optimal breeding programs.  A course in population genetics is called for here.

Mark

 

[knabe]

What if the heterozygote for these alleles has a phenotype that gives the clubby look?  true

Wouldn't heterozygotes for these alleles be given an advantage (albeit an artificial one) in clubby herds?  as in any selection system

Heterozygousity does not mean you are going for an ultra high performance, intensive cross breeding system it is useful in extensive range cattle situations where weaning weights never get above 600 Lb all the way to getting European double muscled cattle that cut out at 80% at 15 months old and 1500 LB.  In both cases heterozygosity makes these goals easier to achieve.  one purpose of a "purebred" is to guarantee heterozygosity in the F1.  being homo for desirable genes guarantees this.

Lastly homozygosity is very rarely the preferred state.  It has been shown since the 1960's that heterozygosity is in fact the vastly more common state.  exactly.

The paper that started it all:  Lewontin, R. C.; J. L. Hubby (1966). "A molecular approach to the study of genic heterozygosity in natural populations. II. Amount of variation and degree of heterozygosity in natural populations of Drosophila pseudoobscura". Genetics 54: 595–609.

This paper started an industry looking into genic polymorphism with citations into the thousands.  It is a pity that Animal Science programs in the United States have not used findings in population genetics in designing optimal breeding programs.  A course in population genetics is called for here.

i've read the paper a couple of times in college.  the key is natural populations.  all breeders are, are imposers of founder effects.  the effect of homozygosity can be seen in corn where one maintains inbred lines and sells the F1's.  the F2's are useless, where one could cull either 75%, or 25% depending upon information available.

the problem is that the entire maine breed has no diversity and is getting worse.  all i'm trying to do is eliminate up front some things, include some things, maximize homozygosity for additive genes and guarantee some diversity by getting rid of the diversity everyone already has that is causing problems.

 

[Mark H]

Knabe,

Your comparison of hybrid corn performance degradation over successive interbreeding generations (F2, F3.. etc.) is valid for plants and other selfing organisms since in this case inbreeding is being reintroduced and homozygosity increases over successive generations thus lowering performance.  Plenty of evidence exists from synthetic lines of cattle that as long as heterozygosity is maintained performance is maintained.  The trick is not to let the selection process become a driver of increases in the inbreeding coefficient.  Data from Clay Center and the University of Alberta back this up.
Lastly, I am interested in a contradiction in your stance.  You want to fix alleles for additive traits and get rid of deleterious genes something that will demand rigorous inbreeding and selection;  yet you are concerned about lack of genetic diversity in the U. S. Maine Anjou herd book.  If you are trying to fix "good" additive genes why are you trying to add diversity?  Wouldn't that put you further from your goals?  Also how to plan on fixing additive traits with out affecting the rest of the genome?  Bio tech manipulation?
If you want genetic diversity have you considered importing semen from France?

 

[Dusty]

this one is getting good...

 

[knabe]

Knabe,

Your comparison of hybrid corn performance degradation over successive interbreeding generations (F2, F3.. etc.) is valid for plants and other selfing organisms since in this case inbreeding is being reintroduced and homozygosity increases over successive generations thus lowering performance.  Plenty of evidence exists from synthetic lines of cattle that as long as heterozygosity is maintained performance is maintained.  The trick is not to let the selection process become a driver of increases in the inbreeding coefficient.  Data from Clay Center and the University of Alberta back this up.
Lastly, I am interested in a contradiction in your stance.  You want to fix alleles for additive traits and get rid of deleterious genes something that will demand rigorous inbreeding and selection;  yet you are concerned about lack of genetic diversity in the U. S. Maine Anjou herd book.  If you are trying to fix "good" additive genes why are you trying to add diversity?  Wouldn't that put you further from your goals?  Also how to plan on fixing additive traits with out affecting the rest of the genome?  Bio tech manipulation?
If you want genetic diversity have you considered importing semen from France?

no venture worth pursuing would not be fun if it didn't have hypocrisy

this may sound ridiculous, but it may be beneficial to take out performance due to heterozygosity OUT.  maines have too many defects, and one way to get rid of them is to create a bottleneck, while retaining additive genes in a homozygous state.  the reason there is no diversity in the herd book is too few bulls with too many defects got distributed.  it's actually pretty amazing how many animals it has taken to get to this point, and one still hears the dominant complaint of soundness.  to be more clear, what i hope to do is to keep the additive genes, and retain diversity in the "rest" of the genes.  the reason for diversity, is that maines have lost the basis for why they were important in the first place other than growth.  you can't get it back from what exists with the cleft palette, monkey mouth, PHA, TH, spastic pareisis, arthritic, low fertility, sickle hocked, low milk, excessive muscle etc., bottleneck that has been promoted.  so, "deselecting" for these supposedly advantageous genes in the heterozygous state is a form of linebreeding.  i'm not naive enough to think that the non-carrying allele of the defective gene might not be important.  this is why i have picked two half brothers from PHA carrying lines, one with milk, one with less, to cross on a low milking carrier line as well as a heavy non-carrying maternal line albeit 2-3 at a time.  what's most interesting in that comparison, is the level of motherhood that has been taken out of "modern" maine genetics .  adding additive genes in a bottleneck is pretty easy.  no manipulation necessary.  already did it and eliminated a defect with odds on one at 1 in 14 which includes being female, didn't get the polled and lost big time on that as both parent were polled.  the odds on that one would be 1/16 if one didn't preknow status at the time which i didn't, and even bigger if i would have got polled.  the key is accumulating 100% odds.  each addition at 50% odds increases the number of offspring necessary to get the state to 1 in 4 for each allele.  so, just as PHA was concentrated in the herd, it's just as easy to impose an economic survival trait, while still within the confines of current economic reality, which, i gotta say, may do more to change cattle than at any point in time.  everyone is going to save the 70 chevelle ls6 models, when one only needs a straight 6 with a variable lobe cam (yes, i know it's contradictory with cow size and efficiency discussions).  preknowing is obviously the key, and minimizes the fuss with all the supposedly high number of individuals necessary to do something different.  i want to do the easy part last.  it's too bad the easy part was done first with maine's.

i used to cry at laguna seca when the bmw's would always beat detroit.  an interesting story about can am racing when 917 porsche's ruled.  the aluminum big blocks could out time trial them, but they needed too much advance, were normally aspirated, and to last the race, they needed to be detuned.  i loved watching them come off the hill in the air.  of course once someone did a back flip, they had to change the configuration.

all the above said, it's pretty obvious that there's a lot of good maine's that are not black, not polled, and not almost solid.  these were the first to go and still continue to go.  pretty clear how to add diversity and who to use now.  it's still pretty surprising how few homo solid bulls there are out there and the "good" one's are not homo solid, still.  i guess the midas bottleneck is not popular for some reason.