If both copies of the gene are mutated, then each gene can make the right protein about 5 to 10% of the time. Affected Dobermans are thus producing von Willebrand factor
Diversity and Recombination
In mammals, DNA is not just one continuous strand, but exists within the cell nucleus in a number of pieces of genetic material called chromatin. Before a cell divides, the chromatin collects itself up into a structure called chromosomes. Dogs have a total of 78 chromosomes, humans have 46. The total number of chromosomes is called the diploid or 2n number. The point of this division is so one member of each chromosome pair can become part of a gamete, or sex cell (egg and sperm). These gametes have half the number of total chromosomes (termed haploid, or n), so when they join together the resulting progeny will be 2n. The sire contributes 39 chromosomes and the dam another 39. They form into matching (homologous) pairs that have the same type of genes on them, but not necessarily in the same form. For instance, the gene that codes for albinism exists at the same position, on the same chromosome, in both parents.
However, one parent has the gene that produces pigmentation and the other carries the gene that produces no pigmentation. The same gene in a different form is called an allele. If the genes are of the same form then the dog is homozygous at that position. If the animal has different alleles at a certain location, then it is said to be heterozygous. In a diverse population, almost every gene has multiple forms of the same gene. This is known as genetic diversity. Another genetic process, called recombination, further adds to genetic diversity. This is how it works.
Prior to division a cell duplicates its DNA and in the process four chromosomes are produced: two sets of homologous (matching) pairs. Before the cell divides these homologous pairs line up and sometimes they swap DNA. This DNA swapping process is called recombination. If the original pair was heterozygous (not matching) at two genes, say A and A+ and B and B+, then the possible gametes formed would be AB, A+B+. A B+, and A+ B. Without recombination, if the A allele was on the same chromosome as the B allele, they would always be inherited together. In fact, such “linked” chromosomes more often than not are inherited together, because the chances of such a split and subsequent recombination decreases the less space there is between the two genes. When recombination does occur, [Susan, I think we must have some graphics here?otherwise no one is going to get it( JCC)?agreed (DCC)] two gametes would be parental types and two of them would be a combination of their parents. Without recombination, traits carried by genes on one chromosome would always be inherited as a group, and dogs would basically only have 39 different “gene-groups.”
The take home message should be that recombination adds to the genetic diversity. This is especially important in a highly in-bred population, such as a specific dog breed.
Do breeders want genetic diversity?
Dog breeders do NOT want genetic diversity, except in certain breeds in which function is still considered the number one priority. For most breeds they want to fix “TYPE”, type being the phenotype or how the dog looks as opposed to genotype, the genetic makeup of the dog. In order to produce type, dog breeders have produced a highly in-bred animal with multiple genes that are homozygous for those traits that specify their breed.
Unfortunately, along with introducing and refining those traits, a plethora of deleterious genes came along for the ride. Our job now, as breeders is to somehow retain those genes that express our breed’s type and yet remove those that cause disease and genetically transmitted defects. Before we can really explore how a particular trait is transmitted or lost within a closed breeding group we will need to introduce and explain such concepts as founder effect, inbreeding depression and linkage disequilibrium. What is briefly introduced here and expanded on in the second article will be a short course in Population Genetics, the technical name for what happens to the gene pool from which reproductive selections will be made.
What Happens When We Lose Diversity?
One of the purported purposes of breeding purebred dogs is to not only improve the breeder’s own stock, but to ultimately improve the breed. The degree to which one breeder can influence the genetic direction of a breed is influenced by many factors; one of the most important is the size and diversity of the existing breed population. In the long scheme of things, individual dogs will live and die, but if bred, their genes will live on through their progeny. Thus from an evolutionary viewpoint, a population, or breed, can be thought of as consisting of as the total number of alleles, rather than individuals, present at one time.
This “gene pool” is equal in size to approximately twice the number of dogs in a population, because each dog carries two alleles per gene (except in the case of sex-linked genes). Evolution results when the relative proportions of alleles change with successive populations. The more variability that exists at one locus, the more room exists for evolutionary change. Goals of purebred dog breeders involve increasing, reducing, and preserving various gene frequencies within a population.
Although individual dogs making up the population change, total gene frequencies within the populations remain fairly constant unless four specific situations (mutation, migration, genetic drift, and non-random selection) apply. Mutation provides the foundation of genetic variability, but without the remaining three situations a single mutant allele will seldom become fixed in a population. Migration refers to the introduction of new alleles from another population, and was especially influential in early development of breeds through cross-breeding. Selection is the main tool of the breeder, who chooses which dogs will pass on their genes to the next population. Selection, plus drift, both play a part in the phenomena known as founder effect and inbreeding depression.
Founder Effect
When a new population is established by a sample (founders) drawn from the parent population, as in the development of a new breed, the genetic make-up of the foundation stock will most likely be very different (simply by chance) from that of the original population from which it was drawn. The smaller the sample the greater the probability of difference in that the sample does not fairly represent the parent population. The genome of such a subpopulation with its limited number of founder individuals will carry the alleles of the new group rather than those of the source group. An allele that is quite rare normally in the original population might be very common is the new one, and visa a versa. This, in effect, abruptly changes the kinds of alleles represented and how often they appear. This founder effect is in essence a form of acute genetic drift (variation in gene frequency from one generation to another due to chance). The problem with losing genetic diversity is severalfold. Once lost, an allele cannot reenter the population except through mutation (unlikely) or migration (which, if a breed is considered a population, means either going back to its rootstock from its country of origin or crossing with another breed). Genetic diversity is the foundation of evolution; it may be acceptable to loose deleterious alleles due to selection, but the loss of other unknown alleles due to chance reduces the variability upon which selection can act, and thus the possibility of further evolution. Loss of genetic diversity also can result in inbreeding depression.
Inbreeding and Inbreeding Depression:
You can’t fool Mother Nature.
Evolution is thought to be a gradual change in the kind and frequencies of alleles. Those mutants that are harmful are either eliminated or kept at low frequencies by natural selection. However; with artificial selection , especially when a breed is being developed, it is the individuals that exhibit the greatest expression of the desired traits that are chosen to breed the subsequent generations. When only a few dogs are used to produce the next generation, a high proportion of their genes will be in the next population of potential breeding animals. When these related dogs are then interbred, the chances of them passing on the same allele that they both received from their sire and dam is 25%. Thus, inbreeding increases the chance that subsequent offspring will carry identical copies of the same allele (be homozygous at that locus). Increasing inbreeding increases the chance of homozygosity and can lead to the loss of one of the alleles from the population.
Breeders walk a tightrope between needing to reduce genetic variation to maintain uniform breed type and needing to maintain genetic diversity to avoid inbreeding depression, which results from homozygosity of deleterious alleles. The majority of alleles detrimental to life and reproduction tend to be recessive, for the simple reason that if they were dominant, they would have been expressed in the individual’s phenotype, and that individual would have been less likely to reproduce. If recessive, only those individuals with homozygous recessive alleles would be reproductively compromised; heterozygotes would be unaffected. Every dog (and every human) carries deleterious recessive alleles, so the chances of the foundation stock carrying them is virtually 100%. If very few dogs were used as foundation stock, their progeny would have to be interbred, and in only a few generations all of the dogs would be closely related. Breeding closely related dogs is inbreeding. An inbred dog has a greater likelihood of receiving the same allele from both its sire and dam, and thus a greater likelihood of being homozygous for a deleterious trait. In an inbred population, as long as the animals can still reproduce, this homozygosity can become fixed in the population due to the chance loss of the other allele. What this means for the breeder is that too great a reliance on inbreeding will lead to loss of ‘fitness’, i.e., failure to reproduce. Fewer litters are produced, the number of whelps will decrease and those that are born will fail to thrive. Taken to extreme, the effective breeding population could be so diminished that the breed would face extinction.
Bottleneck
Modern dog breeds have all been subjected to a founder effect, and many of them have had their gene pools further reduced by subsequent genetic bottlenecks. The best-documented case of a canine bottleneck was created by World War II, when hardships in Europe made it impossible to keep many dogs, especially giant ones. The populations of giant breeds in Europe were practically decimated after the war, and some breeds had to rely upon only a few survivors or imports from less affected areas?in effect, reducing the gene pool and creating a second, even more limited, foundation for the breed.
Other bottlenecks are created when a breed, for whatever reason, becomes extremely unpopular and rare, or when dogs from one country (or worse, one kennel) are used to found the breed in a new part of the world. Yet one of the most pervasive bottlenecks is brought on voluntarily by breeders: the rush to breed to only a few favored sires, the ‘flavor of the month’, while the majority of potential breeding males are never bred.
This bottleneck is made all the worse by the fact that the majority of breeding bitches are often sired by a handful of the last generation’s “favored sons”. In fact, the effective population size can never be greater than four times the number of males in a population, no matter how many breeding females exist . In certain rare breeds, their effective breeding population is thus so reduced, that they are in effect, in a genetic cul-de-sac.
Conclusion
We have considered the origin of the dog, how it evolved from precursors and how initially there was tremendous genetic diversity within the species. We then examined how mutations occur and contribute to that diversity. It was then necessary to introduce those factors that reduce diversity when new dog breeds are established, such as founder effect and inbreeding. Our goal was to inform breeders of the dangers inherent in common breeding practices that can exacerbate the problems to the point that viability is lost.
In Part II of this series, we will continue our discussion of some of the concepts involved with population genetics and suggest ways for preventing or correcting the problems associated with highly inbred populations. We will also introduce and clarify such molecular genetic terms as dominant, recessive, and co-dominant traits which are central and fundamental to the breeding selection process.
So fundamental are these concepts that no breeder can honestly claim to be an ethical breeder without a working understanding of the underlying principles. At a still higher level of complexity, but still of extreme importance to breeders in their selections for breeding, we will need to deal with such ideas as penetrance, overdominance and best of all, epistasis. This may seem a little daunting at first, but the health and future of our favorite companion may depend upon what we breeders do now…so hang on tight, as its apt to be a wild ride.