John,
"1. In your opinion are the majority of the animals you have worked with heterozygous animals for the trait of Dwarfism. and as such can a simple pundit's square be used once we know the specific genetic markers that constitute these traits?"
To answer your first question, Yes, the majority of the horses I have worked with are heterozygous for the dwarfism in Minis, that IS why I have worked with them, they have produced dwarfs. I have not gone out looking for horses as many horses as I can that have never had dwarfs, if I did, how could I do any research regarding dwarfism??
The good and the bad is that the good part is there are non-carriers, calculated by statistical analysis of normal offspring, the bad news is that there are a large percentage of carriers that have produced dwarfs. I do not know the exact percentage, people are notorious about denying their horses have had dwarfs. I would educatedly guess at between 1/8 to 1/2 the population, I believe I said this in another thread.
I do look for specific horses that have had a large number of foals (100 or more foals with no dwarfs), which are obviously stallions. I look for those horses because they statisically are suggestive of being Homozygous normal and not to be carrying any dwarf genes. Since I do not know which genes are involved and I do not know where these genes are, you have to use population analysis of inheritance.
What you are referring to is the Punnett Square, where a square is divided into quads and the percentages of inheritance is show regarding genes that are inheritaed in classic Medelian fashion. Below is my meager attempt to show a Punnett Square in this forum typing program. As can be seen with respect to dominant and recessive classic Mendelian inherited genes we can already calculate percentage of affecteds, heterozygous non-affecteds, and homozygous normals. The populations I have worked with show these percentage calculations convincingly.
parent Aa
A a
_________________ Offspring 25% AA homozygous normal
A | | | 50% Aa heterozygous normal
| AA | Aa | 25% aa homozygous affected (dwarf)
parent Aa |________|________|
| | |
a | Aa | aa |
|________|________|
If we know these gentic markers for these dwarfisms we do not need to use the Punnett Square we only need to have a test done.
"2. Have you found examples of homozygous horses for dwarfism?"
Answer is Yes, it is a dwarf. Horses homozygous for dwarfism are dwarfs, they are homozygous for the defective recessive gene, therefore express the gene and only that gene, because they do not have a normal gene that would be dominant over it.
"3. Are the dwarf genes in miniatures for all four types of dwarfism that you have identified found on the same alleles and/or position in the DNA string. If not have you been able to isolate any of them yet."
Your question is a little confusing for what I think you are asking, I will try to decode it and answer it for others to see.
First, I have not identified the actual genes, that is what all this lab work I am doing is. I have only segmented and characterized 4 different dwarf sydromes/characteristics that have shown to be inherited and expressed in a classic Mendelian manner, thus making me able to posture and predict the existence of recessive dwarf genes in the population that are being perpetuated by breeders due to the inferior breeding practices of our forefathers.
In other words, I have seen four very unique types of dwarfs each type having very consistent unique characteristics, consistuting the theory of four different mutations. Using population analysis of the populations of horses I have worked with, these diseases are showing results of being autosomal recessive diseases. Each possible disease is (possibly) its own allele. Lets say type 1, if you are a carrier, you have two alleles at that spot in the DNA, one allele is the normal gene, the other is the defective recessive dwarf type 1 allele. Now apply that to all 3 others. Each disease (each possibly with its own allele) can be and might very well be on any part of any of the 30 autosomal chromosomes in the horse. I am looking for four needles and each are in their own hay stack.
If I had isolated them I would already know the gene that causes the disease. I dont even know the gene for definite that it is the same gene as I have characterized as comparing it to humans or other animals, ie dexter cattle for type 4. Simply put, type 1 is very similar in physical characteristics and inheritance to the human disease AMDM. The human gene mutation that causes the AMDM has only recently (2004) been found, characterized and sequenced! The dexter cattle one has just been found this last year!!
I just now have enough type 1 samples that the UK feels it is realistic to find anything out. Remember, just having a handful of random samples of some diseased organisms is not going to get you very far in anything with genetics. You could spend your life and still not have any answers. Large numbers of samples with parents are absolutely the key to finding a diseased gene relatively quickly.
Also I am the only one working on this in my lab, and the only one in the world, that I know of, that has the number of samples to accomplish anything. Noone else has even had the sense to try to characterize the differences in dwarfs that have been seen for years, until I did 2 years ago. Everyone that I know of that has said they are doing research on this, I asked how many samples they had, if they had parent samples, and if they had pics, and if they knew how inconsistent the dwarfs were and that this might be very complicated etc,etc, and I got every time was , uh...., well, no..... They were basically blindfolded spinning in circles trying to shoot at a moving target, good luck.
I do not have a whole facility looking for these genes, like most large scale human diseases are done with HUNDREDS of millions of dollars used. I hope this puts my daunting task into perspective!!
John
