Genetic

 

     Dr Per Erik Sundgren has been working intensively in Sweden for over 30 years to try to convince the Swedish Kennel Club and its breeders that there is a serious need for better breeding planning in dog breeding.

His extensive genetic knowledge took him to the conclusion that all the well known problems in dog breeding are caused by too much inbreeding in many small populations.

He also collaborated with Swedish Westie club (Alliansen) for years the same way.

These dog clubs have already established new breeding rules among which breeding restrictions from stud dogs and inbreeding restrictions.

Since 2005, the Swedish Kennel Club forbade very close mating, such as between parents and progeny or between full sibs, and such litters will consequently not be registered anymore by the Swedish Kennel Club.

Dr Per Erik Sundgren also advises to avoid mating between half sibs, between a dog or bitch with any of their grand parents or to any of their aunts and uncles. This is what have been the normal rules among our selves in most cultures for thousands of years and of very practical reasons. Breaking such rules will inevitably produce an increasing number of children with inherited defects and health disorders. Dogs’ genetic system complies with the same rules as ours.

His contribution to Swedish dog breeding has mainly been to try to teach breeders basic and sound principles of breeding. He has also produced a computer software to make it possible for breeders to see for themselves the total consequences in an entire breed of their own planning, or rather lack of planning, for the future of their breeds.

This dog breeding software in Swedish language in his web site http://www.genetica.se should be one day available in English.

(update: unfortunatly, Dr Sundgren left us 01.01.2010 and his website does no longer exist)

The genetic article you will read below was written by Dr P.E Sundgren in July 2006.

His goal is to explain to breeders the genetic basis for how and why inbreeding hurts populations.

     

Natural protection of genetic variation

Introduction

     Programs to preserve genetic health in dog breed have been intensively discussed in Sweden in connection with the development of breed specific genetic strategies. Why have breed specific strategies at all become a necessity in dog breeding?
 In nature there are no special breeding programs or strategies to keep species healthy and vital over very long periods of time.
The cause of the inherited disorders observed in so many dog breeds is that breeders, due to ignorance or extreme breeding forced by various forms of competition trials, break down the protective barriers against genetic disorders that Nature has build through out millions of years by means of natural selection.
What kind of barriers do we need to know about to avoid such mistakes?

The Cell

    The body of an animal is although it is a unit, is composed of billons of cells. The link between generations is however only one single cell - the fertilized egg cell. Thus everybody involved in breeding ought to know at least some about how the fertilized egg is protected against genetic disorders.

Genes – protein prescriptions

     The basic function of a gene is to be as a prescription for the cell about how to build a specific protein. There are about 30-40 thousands of gene pairs and as many different types of proteins can be built by the cell. We all need skeletons, muscles, nerve systems, liver, kidneys and all other internal organs. We also need al large number of hormones, enzymes and signal substances to make out bodies work properly.

    It would all be very simple if there were never any changes in the environment. There would be no need for any changes in the prescriptions about how to make a specified protein.
All species have however to adapt to a continuous change of the environment or to live under threat by predators. To be able to adapt to such changes all animals must themselves be able to change their physic and mental characteristics. There is thus a need for flexibility of the genetic system.

    At the cell level the threat from eternal enemies is extremely large. Innumerable micro organisms and viruses are steadily attacking our bodies.
Thanks to their very rapid generation turn over they are able to change the way they make their attacks many times during the normal life time of any larger organisms such as mammals.
To defend oneself against all such attack each individual need a defence system which id as unique as possible. Otherwise a successful attack on one individual will be rapidly spreading.

The Gene system is subjected to three apparently incompatible demands:

Stability to guarantee that all organ systems are working correctly

Balanced variation for entire population to make long term adaptation to changing environment possible.

Individual variation to protect every being against diseases and infections.

    During the first about 3-4 billion of years on Earth there were no more complicated forms of life but single cell organisms. The normal way of reproduction was a non sexual simple cell division.

     The DNA molecule, the basic element of genes, is a surprisingly stabile chemical compound which by doubling is transferred in equal amount to both the new cells after a cell division. After such a division both cells gets identical genetic make up. But if all cells get identical genomes there can be no genetic adaptation to changes in the environment.
A sudden change of the DNA molecule, or a single gene, may cause the death of the individual since a vital protein can no longer be produced. A single set of DNA molecules or genes has thus serious disadvantages both for individuals and for the long term adaptation of species. Only very simple organisms may survive such lack of genetic variation.

Gender and the duplication of the genome

     After several billion of years Nature found a solution the vulnerable system of simple cell division. Cells with identical gene set up joined two by two creating a new type of cell with a new type of genome carrying a copy of each single gene.
Thus they had an intact copy of the protein prescription should the other be damaged of any reason. Cells of that kind are much less affected by damages to single genes.
There will normally be a duplicate gene to guarantee that the right kind of protein will be produced in sufficient amount.

    Cells with duplicated genomes can no longer multiply by simple cell division. To make the amount of DNA, and thus the number of genes, constant over generations they have to go through two cell stages.
At the first one they divide into two cells with only half of the DNA in each if the two new cells. At the next stage two such halved cells melt together in a fertilization two make a new cell which again carries a genome with duplicates of every gene.

    The solution by Nature was to create two sexes both having special organs, ovaries and testis, where the reduction of the genome to half the normal size takes place when creating ova and sperms. The central advantage of two sexes is the thus the duplication of genes to avoid disastrous results of damages to single genes.

     A system with two sexes has another important advantage. At the stage when germs cells, ova and sperms, are created the DNA molecules, which are as long strings, wraps around each other. As everybody knows it may be a complicated matter to untangle strings
This is so also in the cells, where the paired chromosomes break and exchange parts with each other. This is called over crossing. Thanks to over crossing new gene combinations are formed every generation, and in all individuals, within all species having two sexes.
Sex thus both has the function of protection against gene damages and as an important source of new genetic variation to facilitate necessary genetic adaptation to changing environmental conditions.

     Most but not all chromosome changes are harmful. If there is only a minor change in the composition of a protein due to a mutation, a sudden change in a gene, the new protein may do well in spite of the change. In rare cases the new protein composition might lead advantages for the animal.
Such advantages will rarely show immediately but might result from later crossing over and rearrangements of genes along the chromosomes. In cases where such mutated genes causes increased vitality of animals the carriers will on average produce more offspring and the favourable gene will incorporated into the gene pool of the breed ors species.
In the opposite case, where gene changes are harmful, the mutated gene will be rapidly erased from the population by natural selection. The main selection force is again changes in vitality resulting in less progenies produced by affected animals.

Male to female bond affects male reproduction

     Evolution through out millions of years has shown that the division of animals into males and females has been indispensable for the creation of highly developed animals. There is however a problem connected to the way bisexual mammals reproduce.
The reproductive capacity of females is generally restricted to produce progenies in tens rather than in hundreds. Males may however mate with a large number of females and thus have much more progenies than females.
Such sexual behaviour reintroduces the risk that two genes with identical origin will come together in succeeding generations. Male sexual behaviour may thus violate the protective force of the duplicated gene structure.

     Natural selection again found a solution by creating more or less strong bond between reproducing makes and females. It does not matter if such bonds are for life or only for one reproductive season. The effect will be the same.
The upper limit for male reproduction is set by the number of progenies an average female may give birth to and rear. The creation of male female bonds is a simple and brilliant way in which Nature reinforces the protection caused by the duplicated gene structure in spite of the fact that males have the capacity of producing a dangerously large number of progenies.

     In Sweden an overproducing male with too much progenies is called a "Matador". Matador was an intensively used bull in the northerly part of Sweden. He carried a gene for testicular hypoplasia, too small testicles, casing reduced fertility.
Due to the intensive use of the bull the deleterious gene spread rapidly over the entire local population. I took several decades of selection against the gene to repair the damage caused by too intensive use of what once seemed to be a male of exceptional high quality as a breeding animal.

MHC – the ID card

     The cooperation of billions of cells in a body can only take place if there is a way for all the cells to identify each other as belonging to the same unity. Otherwise there is no way to identify enemies and defend the body against invasion of other cells causing diseases or damages to the body.
Thus each cell in the body needs an identity card. The identity code of the card should vary as little as possible among cells belonging to the same animal but at the same time be as unique as possible for each animal.

    Nature has solved the problem by creating a special set of genes called MHC, where MHC stands for Major Histocompatibility Complex. Together the MHC genes form the unique "identity card" carried by all cells of an indivuidual and make it possible for the cells to cooperate without harming or attacking each other.
The MHC genes constitutes the base for our immune system and play an important role in reproduction.

    The genes of the MHC system create special proteins on the surface of each cell. It is the special combination of these proteins that make up de identity code, alike for all cells of an individual. The cells can "read" each others identity code and cooperate without any risk with cells carrying the same code as them selves.
 If cells carrying another code penetrate into the body they are attacked by special guard cells called T-cells or murder cells. The T-cells are continuously moving around and looking for cells with deviating identity code and kill such cells immediately when found.
Together the combination of the MHC proteins and the T-cells make up one of the most important defence mechanism against invasion of pathogenic cells.

     It is now obvious that the more unique identity code an individual carries the better it is protected against diseases. Pathogenic cells will always try to copy the identity code to fool the T-cells that they belong to the body.
But if they succeed and all individuals carries different identity codes the pathogenic cells cannot spread easily form one individual to another. They will be discovered by the T-cells of any individual carrying another identity code.

    The basic consequence of inbreeding is to duplicate genes of the same origin. Such duplication will inevitably reduce the number if genes with different prescriptions for protein production and hence also reduce the possible variation of genes in the MHC system.
With fewer proteins as a base the identity code will be less unique and easier to copy just as very short keys in a computer system. This is why inbred individuals are more susceptible to infectious diseases.

Genetic scent signals

    Nature has created a special protection against dangerous reduction of genetic variation in the MHC gene system. Again the solution is brilliantly simple. The genes of the MHC system take part in the production of the scent substances called pheromones.
The pheromones are important sexual signals and make it possible for animals to "smell" part of the genetic set up of the MHC genes carried by a possible mating partner. It has been shown by experiments that all kinds of animals from insects to mammals use the pheromones to avoid mating with close relatives carrying all too much of the same genes in the MHC system.
Thus the bond between the pheromones and the MHC genes protects the genetic variation of the immune system. This kind of protection will be effective only when there is a free choice of mating partners and the number of possible partners is large enough.
If the number of available partners is low females may choose to mate also with closely related males rather than not mate at all. A less viable progeny may be better than to become barren.

    It is important to accept when the bitches distinctly signals that they do not accept a male. The females know better than the breeder if the male carries MHC genes which are favourable for her progeny. Forced mating is an effective way to violate one of the most important protections of genetic variability.

Fertility and inbreeding

     Most breeders are well aware of the fact that strong inbreeding has negative effects on viability, health and fertility. But what are the common causes affecting the immune system as well as reproduction making both susceptible to inbreeding.

The feotus is protected from being rejected

    Everybody is well aware of the problems in transplantation surgery to get the receiver accepting foreign tissue. The basic reason for the rejection of foreign tissue is that all it cells carries another ID code and hence they will be attacked by the immune system of the receiver to avoid an unwanted invasion of possibly malignant cells.
When transplanting organs from one individual the process if facilitated if the genetic system of the donor is as alike the genetic system of the receiver as possible. But even in cases where donor and receiver are closely related it is necessary to use cytotoxin to avoid the rejection of the transplanted tissue.

     The genes of a fertilized egg are to 50 % inherited from the mother and tom 50 % from the father. Hence the genetic system of the fertilized ova normally deviates to a large extent from that of the mother. As a consequence the fertilized egg ought to be repelled by the immune defence system of the mother. As a matter of fact should there be no other mechanism at work pregnancy would not be possible.
But again Nature has found a solution. A very special type of protein is produced in the mother to prepare her for pregnancy. That protein has the function of guarding the foetuses against attacks from the immune system of the mother. The special protein will guard the foetuses all the time during pregnancy.
It is an interesting fact that the total amount of foetus tissue, including the placenta, shows a rather constant proportion to the weight of the pregnant female. On of the probable mechanism that releases delivery might then be that the total amount of foetus tissue exceeds the capacity of protection from the special protective protein.

     The protection of the foetuses has a negative side effect. At the time when the delivery is finished the protective protein still remains in the body of the mother for 2-3 days. During these days she is extremely susceptible to infections since her own immune response is seriously lowered by the remaining protective protein.
It is thus necessary to supply the bitch with a clean and dry environment especially during the first few days after delivery.

     One might think that foetuses with gene systems very like their mothers, i.e. for example those that are heavily inbred, would benefit from their genetic likeness to the mother. There should be a less strong tendency to reject such foetuses from the womb.
But if there is a very strong genetic likeness between the mother and her fertilized eggs another problem arises.

    How should the uterus of the mother be able to identify fertilized eggs as deviating from any other cells of her body floating through? The different genotype of the fertilized egg and the mother is most certainly one of the prerequisites for the formation adhesion of the egg to the uterus wall and the formation of the placenta.

     Another risk with to much genetic likeness between the mother and her progeny is that the labour pains during delivery will be seriously lowered leading to a prolonged time of delivery.

     There is thus a threefold advantage in divergent MHC genotype between the mother and her progeny. The foetus will get a better start in uterus of the mother, the delivery process will be shortened and thus less trying and finally the new borne animal will have a more unique ID code making it more viable and less prone to get infectious diseases.

Number of puppies and size of the mother

     One of the fascinating consequences of the fact that the total foetus tissue has a rather close relation it the size of the mother is that affects litter size in dogs. Normally there is a negative relation between size of the mother and number of progenies in al litter, i.e. the larger the mother the fewer her progeny in each litter.
Small animals like mice tend to have large litters while large animals like elephants normally give birth only to one young at a time. In dogs this rather general rule is reversed, as in most breeds of domesticated pigs. The reason seems to be that our breeding efforts have been much more effective in changing adult size of our dogs than changing the size of their new borne puppies.
Thus with the same proportion of foetal tissue compared to the body weight of the female a large female will be able to carry more puppies.

The ova and her selection of sperms

     Is there any way in which an unfertilized egg may have any influence upon its genetic variation after fertilization? Anybody who has seen pictures of egg just before fertilization knows that the egg is surrounded by a crow of sperms.
It is not just a coincidence or an act of Natures superabundance that there are millions of sperms produced to fertilize only one or a few eggs. The large amount of sperms is a guarantee that enough number of sperms will reach the egg in time for fertilization.
The identity code of all cells will then make it possible for the egg to select a sperm among all available that best matches her own MHS complex so as to produce as viable a progeny ass possible.

     It might sound strange that an unfertilized egg should be able to select the sperm that is allowed to fertilize her. But fertilization is not a violent process where the sperm forces its way into the egg.
The cell wall of the egg has to open up to let the contents of the sperm pass into the egg. Thus the egg cell takes an active, and probably dominant, part in the fertilization.

    Similar mechanisms are since long well known in cross-fertilization in plants. If pollen form the flowers of a plant reaches the stigma of flowers on the same plant the pollen tube will not grow due to blocking chemical reactions. Thus the stigmas if flowers are able to identify the genotype of pollen and avoid close inbreeding and self fertilization.

     The large number of sperms produced by mammal males has the same function as the large number of pollen produced by plants. It gives the female egg the possibility to select a partner producing progenies with the highest possible viability.
Large number of sperms is thus another of Natures guarding system to preserve genetic variability in a breed or species. The use of strong inbreeding will however again break down the protective systems since all the sperms will be too like in genotype and thus reduce the possibility for the egg to select a proper sperm.

Artificial reduction of number of sperms

     The very large number of sperms normally produced by a male has since long been seen just a surplus overflow with none or futile effect in breeding. The argument behind seems to have been that as there is need for only one viable sperm to fertilize one egg why not try to make fertilization more effective.
The number of sperms produced at one occasion will certainly be enough to get much more females pregnant. Prominent males can then used to a much lager group of progenies than ever seen in Nature.

    In breeding with cattle using artificial insemination one normally dilutes the ejaculate 1/100, i.e. the number of sperms will reduce to only one hundred of the normal number. Although such a reduction may not have any dramatic short term effects it is obvious to anybody thinking clearly that in the long term perspective the effect might be deleterious to the genetic variation and thus to the viability of animals.

     With our selves the experimentation has gone much further. It started by test-tube fertilization. With this method, as when insemination, the fertilization as such is quite normal although the number of sperms is often reduced.
Toady one often uses what is called micro injection. In that case some scientist or doctor is looking through a microscope trying to find a viable sperm, i.e. one that swims around and looks alert. Such a sperm is then picked up into a micro pipette which is forced through the wall of the unfertilized egg. When using micro injection to fertilize the egg it is totally depleted of all possibilities to select a sperm that matches its own genotype to guarantee as viable progenies as possible.

     The fact that it might not be possible to immediately, or in a few generations, detect serious negative effects due to such violent break down of natural security mechanism is not a proof of that the technique is not harmful in a longer time perspective.
Evolution works through many small steps. Each of those steps may seem to be of minor importance but added over a large number of generations the may have profound effects of the development of a breed or a species.
 Therefore one cannot by the experiences from but a few generations conclude that it is harmless to pull down all security mechanisms built into the system of fertilization to preserve vital genetic variation.

Surplus of eggs at each mating

     Among multiparous animals there is also another and simpler mechanism to enhance viability among the new borne progenies. The number of ova shed by the females during the heat period is normally about twice the number ever born as fully developed young ones.
If the female is mated in e favourable time of heat alls the ova will be fertilized. But there is rarely enough with place for all the fertilized eggs in the tubes of the uterus. There will thus be a competition among the eggs for a place where they can adhere to the uterine and start the formation of a placenta.
Less viable eggs, for example such eggs that have got duplicated genes with negative effects on very early development, will lose the competition. Hence the young ones borne have a little less of genetic burden to carry. The actual inbreeding is a little bit less than the one that may be calculated from their pedigrees.
This type of selection will never be as strong as the one base on selection among millions of sperms. But it will guarantee that genes with profound negative effects on early development cannot easily spread in a population.

Natural selection

    Natural selection, or the forces applied by nature to make individuals as viable ass possible in their environment, will not preserve genetic variation in all genes systems. In some cases there is need for genetic stability.
As living creatures we all need lungs, hearts, stomachs skeletons, nerve systems and brains and so forth. It would be harmful with too much of genetic variation in the genetic systems responsible for development of our basic organs.

    What we in everyday speech call the natural selection is a force with the purpose to balance the genome to give it the best combined effect on viability. In nature a creature has to find food, protects itself against enemies including micro organisms.
It is also necessary to be able to adapt to environmental factors such as heat or cold, rain or lack of continuous supply of water. If en an individual shall have any impact on the genetic future of the species to which it belongs at has to find itself a mating partner and produce and rear progenies.
For the females also the very complicated process of pregnancy and delivery has to work without problems. A lot fewer animals than people normally know of survive long enough under natural selection to pass all the necessary stages as contributors to future generations.

    It is of profound importance that all breeders of animals do understand that the basic principle of natural selection is to stabilize the genetic system to be effective during normal environmental circumstances.
The struggle for life in nature has very little to do with fights between individuals. The main fights are the fights for survival and reproduction. Only those who in the long run produce viable progeny are the winners and in nature extreme individuals are not among the winners. The most prolific individuals will win the race and those are the one best adapted to the present environment, i.e. the normal individuals closer to the population average.
In a case where changes never take place in the environment natural selection would probably result in a very far going genetic identity between individuals of the same species. But environmental circumstances always changes and over long time periods the changes may be very large. Species that have lost their genetic variation will not be able to adapt to those changes in environment and hence their destiny is extinction. Of this reason Nature will always favour those species that has the power both to preserve the genetic variation necessary for adaptation and to preserve the genetic stability to form all vital organs of the body.

    Normally there is genetic variation in systems responsible for body size and form, colour, length and thickness of the fur and so forth. Those are example of characteristics that it may be favourable to be able to change rather rapidly if environmental conditions undergo sudden changes.
Other gene systems, as for example those who are responsible for reproduction, may be more stable. Food supply may for example vary quite a bit between years and it would not be an advantage if that had an immediate genetic effect to reduce reproductive capacity.

    In wild animals the selective force will under all normal circumstances be directed towards the centre of the population – the average individual is rewarded. Extreme individuals may have advantages only in cases where the environment changes dramatically.
If the temperature for example drops heavily, such as for 65 million of years ago, animals with long and protective fur may get a selective advantage and form the new centre of a population. Should the change be large enough a new species is actually created.
 In cases where such environmental changes are very rapid or too large, there might be no animals carrying the necessary genes and characteristics to survive. Then the entire population ore species will become extinct.
That has actually happened to over 98-99 % of all species ever existing on Earth.

     In Nature a stabilizing selection, adapted to small and slow environmental changes is the normal state. The rapid environmental changes are rare but most of them cause widely spread extinction of living species.
The very rapid loss of species today, as a consequence of our civilization and its effect on the environment, may serve as a commonly known effect of the difficulties species have to adapt to too sudden changes of their living conditions.

Artificial selection

     Artificial selection is the selection of animals by man. When breeding farm animals there is a steadily ongoing selection for faster growth, more milk or eggs and meatier animals. The most extreme individual are those who win the race provided they are able to cope with the burden of rapid change placed upon them.
Breeding pet animals should be possible without such an ambition to rapidly change animals. For most per animals however the breeding is governed by show competitions or other trials such as hunting trials and working trials for dogs.
In a contest there is no way to, as in natural selection, favour the most average individual. In a contest the extreme individuals are the winners. In all too many cases but small differences in characteristics of none or indeed negative consequence to the health of an animal will be rewarded. As a matter of fact the artificial selection applied to our animals, also the pet animals, very much like the type of natural selection during environmental catastrophes.
Extreme individuals are primarily the ones selected for breeding. The negative effect of such a selection policy over a long period of time is well known. The problem in pet and dog breeding is that most people do not plan for at best more then decades, very few for longer periods and none that cares for the effects measured in evolutionary time perspective.

    If we seriously want to breed and rear healthy and vital pet animals we have to learn all the ways Nature preserve viability in wild animals. We must abandon breeding techniques that invariably violates all the security mechanisms invented by Nature.
 If we are not willing to learn how these security systems are built, and how we can use them in favour of our loved animals, both breeds of farm- and pet animals may get a depressing future. Breeding is not primarily a matter of complicated genetic theory.
 The Nature has no theoretical knowledge of genetics. Successful breeding, with the intention to create healthy and viable animals, is a matter of adopting and stick to some few and very simple roles of selection and breeding.

Summary and some practical consequences

     At this stage it ought to be evident that the overriding cause to genetic defects and inherited diseases in animals not is due to some unhappy coincidence. It is the direct and unavoidable consequence of lack of knowledge among breeders about some basic rules of Nature.
 They have not had knowledge enough to foresee the consequences of the way the have used their animals in breeding. The force most responsible for all the mistakes made is the basically unsound breeding or contests and trials where rapid genetic changes in desired directions have was given higher priority than the health and viability of the animals.
 The rewarding system applied in competitions also stimulates to split breeds into steadily larger number of breeds or varieties of breeds. This inevitably produces a large number of populations all too small for any kind of proper breeding. When the number of breeding individuals gets below critical levels the loss of genetic variation is very rapid. Genetica disorders may be a problem is such a short time as about ten generation or 30-50 years.
 Most breeds are not older as pure breeds then about 100 year. The steadily growing problem with genetic disorders in our pet breeds is thus exactly what is expected from what we know about breeding practices in many breeds.

     Those who are looking for advanced breeding programs to correct all the genetic problems we see today are looking in all the wrong direction. They should try to understand exactly what has gone wrong and start to learn form Nature how animals can be kept viable over hundreds and thousands of years without any theoretical knowledge at all.

The size of a population must be large enough to carry and preserve genetic variation. There is no way to succeed when breeding population having les than about 100-150 breeding animals and twice the number is preferable.

Only viable animals in good physical and mental condition and all natural functions still present should be allowed to breed.

In highly developed creatures the basic rule is that separate individuals are not allowed to have more than a restricted number of progenies during its life.

     Those are the three simple basic rules of Nature, rules when properly applied will keep any population of animals healthy over very long time periods. The one and only reason for the genetic disorders in our breeds of dogs and other per animals is that we neglect to consider the mechanisms to protect genetic variation created by natural selection during billions of years.

Sprötslinge, July 2006

Per-Erik Sundgren

Dr. Agric.