Re: [PyrNet-L] SAS- Threat to Pyrs?

[Kshoffman@aol.com]

In a message dated 12/19/99 7:20:48 AM Eastern Standard Time, 
JGentzel@aol.com writes:

<< While I appreciate Janice's observation and would not want to make any 
 comments that are negative in the least, I have a huge alarm going off in my 
 head.  The alarm says lets not make such a huge jump in theory and casual 
 observation that could be exacerbated by bias and mistakes.>>

True, a controlled scientific study and statistical analysis of the data, 
accounting for all possible variables, would be a more reliable indicator of 
whether or not decreasing levels of homozygosity (reduced coefficients of 
inbreeding) in Newfs is significantly statistically correlated to decreasing 
frequencies of SAS (or other defects) in the breed.  It would be nice if some 
credentialed professionals would take on such a study and test this 
hypothesis, as the results could likely be extrapolated to apply to other 
breeds and other species.

That said, I don't think the casual observation of a possible significant 
link between reduced coefficients of inbreeding (COI's) and reduced incidence 
of SAS is a "huge jump" at all.  The notion that more closely genetically 
related populations (or subsets of a population) experience higher levels of 
genetic defects than more genetically diverse populations or subsets is 
certainly nothing new.  It is at the core of what the study of population 
genetics is all about -- counting and tracking frequencies of both beneficial 
and deleterious alleles across a population, then formulating a plan and 
method for equalizing and balancing the distribution of these in such a 
manner as to maintain as much beneficial genetic material as possible 
population wide, while stabilizing and/or reducing the rate of deleterious 
mutations population wide.

The theory that inbreeding (including linebreeding) in general results in a 
higher rate of defects and less fitness has been strongly suspected and 
speculated on for quite a long time, especially as it regards genetic defects 
in humans, mice, and livestock. What *is* relatively new (especially so in 
the past decade) is that current scientific evidence strongly indicates this 
hypothesis is indeed true, not just opinion or conjecture or gut feeling.  
Additionally, we are now learning *why* and *how* this happens.  The bottom 
line is, genetics is much more complicated than we (specifically as dog 
breeders) have been taught for the past several decades. Our dog breeding 
books are outdated.  It's time to consider some continuing education. 
Knowledge is not static, and that applies to genetics and dog breeding as 
well.

<<Sounds like we cannot exactly pin down the genetic mode of transmission and 
when we might it is like a roulette wheel, we never know when the mutation 
number will hit. >>

Precisely, but what about when it is not just *one* number on the roulette 
wheel, but certain combinations of a series of different numbers that result 
in a "hit", or a "partial hit"?  In such a case, the smaller the amount of 
genetic material one works with, the higher the odds of hitting those certain 
combinations of numbers on the roulette wheel that *collectively* cross the 
threshold and result in some grade of impaired function. The further you 
cross the threshold, the more serious the grade of impairment. It sounds all 
well and good to think that an individual breeder can "eliminate" such a 
multifactorial defect in their breeding program via linebreeding or 
inbreeding, bringing the defect to light, then stringently selecting against 
it, but what if the breeder is only eliminating *part* of the equation, only 
one or two of those "numbers" in the combination, just enough to put their 
stock right below or at the threshold?  A breeder may well be fooled into 
thinking their gene pool is "clean" for the defect, when in fact they may 
have only eliminated but one or two of many factors in the equation.

Just to give an idea on how difficult it might be for even the most skilled 
and informed of breeders to purge such a polygenic defect via linebreeding, 
visit the following URL "Analogy of a Polygenic Trait with a Single Gene of 
Major Effect".  This analogy describes the probable mode of inheritance 
(although likely grossly oversimplifying) of idiopathic epilepsy in Belgian 
Tervuren (my other breed) as based on the research of Drs. Famula and 
Oberbauer at UC Davis and as presented at the AKC Canine Health Foundation 
conference a couple of months ago.  While the analogy uses the example of 
three genes, in actuality, we may be talking about several or more genes that 
in certain allelic combinations, causes a dog to cross the seizure threshold.

<A HREF="http://www.abtc.org/analogy.htm">Analogy for a Polygenic Trait with 
a Single Locus of Large Effect</A>
http://www.abtc.org/analogy.htm 

The researchers focus is on locating the gene of major effect for epilepsy in 
Belgian Tervuren.  However, even when we have a DNA test to identify this 
gene, it won't be a 100% reliable selection tool.  A sufficient margin of 
error will exist as certain individuals who carry the gene of major effect 
will never cross the seizure threshold because they don't carry enough of the 
deleterious alleles at the associated minor gene loci.  Conversely, there 
will also be certain individuals who don't carry the gene of major effect, 
but still cross the seizure threshold because they *do* carry enough of the 
deleterious alleles at the associated minor gene loci.  In Belgian Tervuren 
the estimated epilepsy affected rate of 15+% and the estimated carrier rate 
of the major effect gene is 50+%.

Population geneticists recommend that the stringency of an applied selection 
scheme against any given defect or condition should not eliminate more than 
10% of the gene pool.  In other words, reducing epilepsy in Belgian Tervuren 
is going to be a LONG HAUL, and *realistically*, we will never be able to 
eliminate the defect completely, only to reduce it.  We can't focus total and 
complete emphasis on eliminating epilepsy in Belgian Tervuren when we also 
have a multitude of other health defects to be concerned about.  It's all 
about striking an acceptable balance.

Kelley Hoffman
kshoffman@aol.com