THE MYTH OF INBREEDING AS A MEANS TO PURGE
Bernd Fritzsch, Ph. D.
As a trained biologist,
I have often wondered where the persistent myth that inbreeding is good
for domestic breeds has come from. This is particularly troublesome
in light of the many examples found in the wild suggesting that in nature
inbreeding leads to inbreeding depression, and ultimately to extinction
(Frankham and Ralls, 1998). Therefore, inbreeding is a serious threat
for conservation biology and a real problem where culture meets and splits
natural breeding grounds into smaller and smaller parcels. Consequently,
zoos that engage in captive breeding programs monitor very closely the
degree of inbreeding. In addition, nature has invented schemes to
avoid inbreeding via many different mechanisms. One is known as optimal
discrepancy, where most mating happens between distantly related animals.
Flowering plans have evolved molecular mechanisms to avoid self-fertilization
(Stone et al., 1999). Even the best known case of high levels of
naturally occurring inbreeding, the blind mole rat, has genetic exchange
between the different underground colonies, thus keeping a degree of genetic
diversity not unlike humans and domestic cats (Page and Holmes, 1998).
So, why do we think
that breeding dogs or other domestic animals is any different? While
I can not completely resolve this problem, I found a few reasons that make
it likely why this myth came into existence. One of these reasons
relates to the apparent achievement of fixing a specific type that is so
easily achievable by inbreeding. Any natural breeding will result
in some variation around a given type. In contrast, even inbreeding
over only a few generations will result in reduced variability, thus making
the offspring look more alike because of loss of genes responsible for
the increased variation. We accept the price tag that comes with
this in our food plants and have to defend them against invasion by pathogens
which would wrack havoc in these diversity depleted populations if left
alone (Stachowicz et al., 1999). Similarly, many dog breeds will
not survive in the wild as we have selected for specific features and not
necessary for their ability to survive.
Thus, while inbreeding
is a powerful tool to minimize variation in a desired type, a breeder needs
to be aware of the unwanted effects of inbreeding that will ultimately
result in the extinction of this extremely homogenous line so carefully
generated by inbreeding. This are at least the lessons taught to
us by nature. So, with this knowledge in hand one wonders what other
arguments are there in favor of inbreeding, other then the desire to generate
over the short run dogs that closely fit the standard of the breed.
One argument I frequently hear is that inbreeding is actually beneficial
for a breed as it will unmask deleterious genes and can help eliminate
those carriers. I will show below that this is hardly a reasonable
argument. However, as with many bad science examples, once invented
they can hardly be eliminated because somebody will find the original paper
and simply be ignorant about all the contrary data and re-emphasize the
original idea. After all, we lived for several hundreds of years
with the flat earth myth.
As a biologist
I am afraid to admit that apparently the idea of inbreeding as being beneficial
for reproduction apparently goes back to C. Darwin. Darwin noted,
as have others before him that inbreeding does not appear to be a major
mode of reproduction in wild populations. However, he also noted
that inbreeding in domestic and wild populations causes inbreeding depression.
Astonishingly, one of his lines of morning glory flowers he studied for
this inbreeding depression phenomenon appeared to come out of this inbreeding
depression during Darwin's life time and appeared more healthy than lines
of limited outcrosses. Darwin named this line Hero, for obvious reasons.
From this example, Darwin and others concluded that somehow the accumulation
of bad inherited material can be purged and after an inbreeding depression
of variable length the population may emerge healthy again or even healthier
than the original population.
such purging and exit from inbreeding depression can occur, Darwin had
no idea how frequently that is or whether it will regularly occur.
Over the last 150 years we have learned that the successful exit out of
an inbreeding depression is in fact very rare. Out of 52 published
studies conducted, only two have clearly shown that this can occur (Pennisi,
1999). All other cases showed a lasting inbreeding depression with
no apparent signs of recovery or even extinction of populations.
Moreover, recent attempts to restore fertility in severely inbred populations
by introducing new individuals showed dramatic restoration of fertility
and recovery of local populations from the brink of extinction.
So, what can we learn from these examples
for dog breeding? Apparently, firstly we have to look at fertility
rates of more inbred as compared to outcrossed dog populations of various
breeds. If statistics were to be trusted and claims of fathers confirmed
one would likely see that multi generation of inbreeding will result in
statistically significantly lowered numbers of viable offspring.
The recent public exhibit of the cross of two mutts resulting in 17 puppies
certainly supports the notion of hybrid vigor at the offspring level.
In humans, inbreeding depression causes a 40% lethality or severe disabilities
of offspring produced from brother/sister mating (Page and Holmes, 1998)
and it is a reasonable assumption that this will be comparable in dog brother/sister
The next question
is, of course, what is the scientific basis for inbreeding depression and
the occasional success of purging the genes responsible for this depression
as well as exiting the inbreeding depression as an apparently purified
population. To be honest, nobody knows for sure. This simply relates
to the large number of still unknown genes even in the human genome and
the even less known interindividual genetic variability. Thus it
can well be that the two cases known in which purging seems to have worked,
may have started with less genetic defects than those in which inbreeding
led to extinction. Can we know beforehand whether the population
we want to breed falls into one or the other category? Unfortunately
not! If we would know that, we could redesign our breeding efforts
of endangered species. As far as rare breeds of dogs are concerned,
it is apparently bad advice to bet on the occasional self-healing capacity
of inbreeding. More likely is that the dog breed in question will
fall into the category of disastrous outcome of inbreeding. This conclusion
is supported by a number of clinically relevant findings in inbred dogs
that would have been impossible to achieve in the less inbred human population.
One outcome of
inbreeding is that genes, which we inherit from both father and mother
as two slightly different variations, will be more uniform. Less
genetic variation makes animals look more alike (and thus make them conform
better to a given standard) but also makes them more sensitive to spread
of infections (more difficult in a more heterogeneous population of hosts
for a disease; Stachowicz et al., 1999). The good part is, if one
of these genes is defective and causes a lethal mutation, the carrier will
disappear in the next generation. Thus, some people actuall think
they are able to purify through this approach their line. However,
there are a number of issues this assumption has not resolved. First,
given that any breeder will no be able to breed more than about 25 litters
of multi generations of inbreeding of sister/brother mating (assuming a
mean breeding age of two years for the dogs and a breedering program of
50 years) any breeder will hardly be able to see the outcome of his effort
(either positive or negative). If we look for longer breeding programs
there is a population of lions in India which have gone through almost
100 years (or about 50 generations) of inbreeding. This population
now has the lowest known genetic variation of all wild animals tested to
date (Page and Homes, 1998). While still healthy, it is possible
that any infection entering this population will spread rapidly and erase
the entire population. In contrast to these lions, dogs have been domesticated
for thousands of years and have been selected to a reasonable extent
to serve the whims of their breeders, which are not necessarily compatible
with a dogs ability to sustain its life, a simple fact that rules the survival
of the lions mentioned above.
Another issue relates
to the fact that the differences between the fatherís and the motherís
genetic material tends to be increased by mutations every generation.
This counteracts to some extent the uniformity generated by inbreeding.
In dog breeds which started with small foundation populations and have
been enlarged to several thousand individuals in part by excessive inbreeding
to fix the type, this issue becomes a big problem simply because the selection
pressure applied (conformation to a specific type) does not take all genes
that are necessary to develop an animal into account. Thus, while
focusing on the perhaps 1000 genes relevant for the desired traits, those
breeders (and others before and after them) have ignored the remaining
139,000 genes necessary for a fully functional dog.
One of these dog
breeds that was recently generated from a small foundation population is
the Doberman Pinscher. These dogs have recently featured in a significant
scientific discovery because of their highly inbred background. The discovery
is that a single gene causes, if mutated, a condition called narcolepsy
(Lin et al., 1999). This condition is typically elicited by strong
positive emotions. The dog will jump up, all excited and suddenly
collapse and fall asleep. Because of the highly inbred strains of both
Doberman Pinscher and Labrador retrievers available, geneticists could
isolate the gene involved in this disease, and could characterize how this
gene causes this disease (Lin et al., 1999). However, while this
is scientifically useful, it does not help the breed. Clearly, in
the wild an animal that will fall asleep when it sees a mate or prey will
not survive as an individual nor propagate into the next generation.
Nevertheless, purging by inbreeding would likely not help as the carriers
are normal and show no symptoms. This is in contrast to other inherited
diseases such as human sickle cell anemia. While individuals carrying
two mutated genes are not viable, the carrier of a single mutated gene
is only impaired in his oxygen transport, but otherwise healthy.
Clearly, if a gene does not cause any recognizable phenotype in the heterozygotic
state it can not be selected against, and the lethal homozygotic state
will appear only in highly inbred population in a few individuals (about
25% of each litter).
I often hear the
argument that one should keep a genetically affected animal for test breeding
with presumed carriers. The logic is compelling, so it seems.
Once a carrier has been identified, it will not be used for breeding. Good.
But how about the siblings of the carrier? Do we cull them all?? And how
many test breeding do we need before we can go ahead and breed that dog?
About 25 to make sure that the dog does not carry the most frequent genetic
diseases? And how about the less-frequent ones, and those that are
not yet characterized as being inherited? 25 times 4 puppies would
mean 100 puppies have been produced (and killed) just to make sure that
the dog in question does not carry any of the 25 mutated genes involved
in the arbitrarily defined 25 investigated genetic diseases. This
does not appear to be a humane and efficient way of approaching the problem.
Last, but not
least, in order to do the test breeding you have to have a dog that has
the mutated genes. So, in order to test for the 25 genetic diseases,
you have to have the 25 sick dogs you need for test breeding. Imagine
anyone visiting a kennel to choose a puppy and the breeder shows off with
all the sick dogs they have to do the numerous test breeding to generate
a genetically healthy (for the tested genes at least) dog. Again,
the problems with the test breeding and culling scenario are obvious.http://www.sighthoundmagazine.com
In summary, in
most dog breeds, and in particular in rare breeds, inbreeding is not a
solution but a problem. In fact, the very reason given, unmasking
mutations otherwise unrecognizable, is not a good reason for inbreeding.
If a genetic disease is uncovered by inbreeding, the breeder would need
to eliminate both lines used for this breeding because the heterozygotic
animals can not be detected on phenotype alone. The argument of testbreeding
to a known carrier sounds good on paper but would require excessive culling
of puppies and, minimally, sterilization of the tested lines which are
also needed to generate affected dogs for the next generation of test matings.
It seems, the very genetic techniques that will eventually allow us to
correct these mutations will also allow us to screen for mutations without
going through the peril of inbreeding with its highly unlikely cure of
purging all deleterious genes. Thus, in the next millennium we will
probably be able to debunk the inbreeding myth simply by showing that its
single alleged application, testbreeding and purging, is not a rational
way to handle genetic problems in a breed. After all, wolves are
conforming to their type based on a high genetic variation (Vila et al.,
1997). The challenge will be to generate type in combination with
genetic variation rather than depleting this by excessive inbreeding.
Lin, L., Faraco, J., Li, R., Kadotani, H., Rogers,
W., Lin, X, Qiu, X., de Jong, P.J., Nishino, S., and Mignot, E., (1999)
The sleep disorder canine narcolepsy is caused by a mutation in the Hyporetin
(Orexin) receptor 2 gene. Cell 98: 365-376.
Page, R.D.M. and Holmes, E.C. (1998) Molecular
Evolution: a phylogenetic approach. Blackwell Science, pp. 346
Pennisi, E. (1999) The perils of genetic purging.
Science 285: 193.
Frankham, R. and Ralls, K. (1998) Inbreeding
leads to extinction. Nature 392: 441-441.
Stachowicz, J.J., Whitlach, R.B., and Osman,
R.W. (1999) Species diversity and invasion resistance in a marine ecosystem.
Science 286: 1577-1579.
Stone, S.L., Arnoldo, M.A., and Goring, D.R.
(1999) A breakdown of Brassica self-incompatibility in ARC1 antisense transgenic
plants. Science 286: 1729-1731.
Vila, C., Savolainen, P., Maldonado, J.E., Arnorim,
I.R., Rice, J.E., Honeycutt, R.L., Crandall, K.A., Lundeberg, J., and Wayne,
R.K. (1997) Multiple and ancient origins of the domestic dog. Science