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Pedigree Analysis and How Breeding Decisions Affect Genes

Reprinted by permission, Jerold S Bell DVM

Jerold s Bell DVM, Clinical Associate Professor of Genetics, Tufts Cummings School of Veterinary Medicine

To some breeders, determining which traits will appear in the offspring of a mating is like rolling the dice – a combination of luck and chance. For others, producing certain traits involves more skill than luck – the result of careful study and planning. As breeders, you must understand how matings manipulate genes within your breeding stock to produce the kinds of offspring you desire.

Photo by Dustin Hartje

When evaluating your breeding program, remember that most traits you’re seeking cannot be changed, fixed or created in a single generation. The more information you can obtain on how certain traits have been transmitted by your animal’s ancestors, the better you can prioritize your breeding goals. Tens of thousands of genes interact to produce a single individual. All individuals inherit pairs of chromosomes; one from the mother and one from the father. On the chromosomes are genes; so all genes come in pairs. If both genes in a pair are the same gene (for instance, “aa” or “AA”) the gene pair is called homozygous. If the two genes in a gene pair are unlike (for instance, “Aa”) the gene pair is called heterozygous. Fortunately, the gene pairs that make a cat a cat and not a dog are always homozygous. Similarly, the gene pairs that make a certain breed always breed true are also homozygous. Therefore, a large proportion of homozygous non-variable pairs – those that give a breed its specific standard – exist within each breed. It is the variable gene pairs, like those that control color, size and angulation that produce variations within a breed.

There are ways to measure the genetic diversity of a population. One method is to measure the average inbreeding coefficient (or Wright’s coefficient) for a breed. The inbreeding coefficient is a measurement of the genetic relatedness of the sire and dam. If an ancestor appears on both the sire and dam’s side of the pedigree, it increases the inbreeding coefficient. The inbreeding coefficient gives a measurement of the total percentage of variable gene pairs that are expected to be homozygous due to inheritance from ancestors common to the sire and dam. It also gives the chance that any single gene pair can be homozygous due to inheritance from ancestors common to the sire and dam. It also gives the chance that any single gene pair can be homozygous.

The types of matings that you choose for your breeding animals will manipulate their genes in the offspring, affecting their expression. Linebreeding is breeding individuals more closely related (a higher inbreeding coefficient) than the average of the breed. Outbreeding involves breeding individuals less related than the average of the breed. Linebreeding tends to increase homozygosity. Outbreeding tends to increase heterozygosity. Linebreeding and inbreeding can expose deleterious recessive genes through pairing-up, while outbreeding can hide these recessives, while propagating them in the carrier state.

Most outbreeding tends to produce more variation within a litter. An exception would be if the parents are so dissimilar that they create a uniformity of heterozygosity. This is what usually occurs in a mismating between two breeds, or a hybrid, like a Cockapoo. The resultant litter tends to be uniform, but demonstrates “half-way points” between dissimilar traits of the parents. Such litters may be phenotypically uniform, but will rarely breed true due to a mix of dissimilar genes.

One reason to outbreed would be to bring in new traits that your breeding stock does not possess. While the parents may be genetically dissimilar, you should choose a mate that corrects your breeding animal’s faults but complements its good traits. It is not unusual to produce an excellent quality individual from an outbred litter. The abundance of genetic variability can place all the right pieces in one individual. Many top-winning show animals are outbred. Consequently, however, they may have low inbreeding coefficients and may lack the ability to uniformly pass on their good traits to their offspring. After outbreeding, breeders may want to breed back to individuals related to their original stock, to attempt to solidify newly acquired traits.

Linebreeding attempts to concentrate the genes of specific ancestors through their appearance multiple times in a pedigree. It is better for linebred ancestors to appear on both the sire’s and dam’s sides of the pedigree. That way their genes have a better chance of pairing back up in the resultant offspring. Genes from common ancestors have a greater chance of expression with paired with each other than when paired with genes from other individuals, which may mask or alter their effects.

Linebreeding on an individual may not reproduce a outbred ancestor. If an ancestor is outbred and generally  heterozygous (Aa), increasing homozygosity will produce more AA and aa. The way to reproduce ab outbred ancestor is to mate two individuals that mimic the appearance and pedigree of the ancestor’s parents.

Inbreeding significantly increases homozygosity, and increases the expression of both desirable and deleterious recessive genes through pairing up. If a recessive gene (a) is rare in the population, it will almost always be masked by a dominant gene (A). Through inbreeding, a rare recessive gene (a) can be passed from a heterozygous  (Aa) common ancestor through both the sire and dam, creating a homozygous recessive (aa) offspring.

The total inbreeding coefficient is the sum of the inbreeding from the close relatives (first cousin mating), and the background inbreeding from common ancestors deep in the pedigree. Such founding ancestors established the pedigree base for the breed.
The total inbreeding coefficient is the sum of the inbreeding
from the close relatives (first cousin mating), and the
background inbreeding from common ancestors deep in the
pedigree. Such founding ancestors established the pedigree
base for the breed.

Knowledge of the degree of inbreeding in a pedigree does not necessarily help you unless you know whose genes are being concentrated. The relationship coefficient, which can also be approximated by what is called the percent blood coefficient, represents the probable genetic likeness between the individual whose pedigree is being studied, and a particular ancestor.

We know that a parent passes on an average of 50% of its genes, while a grandparent passes on 25%, a great-grandparent 12.5%, and so on. For every time the ancestor appears in the pedigree, its percentage of passed on genes can be added up and its “percentage of blood” estimated. In many breeds, an influential individual may not appear until later generations, but then will appear so many times that it necessarily contributes a large proportion of genes to the pedigree.

The average inbreeding coefficient of a breed is a measurement of its genetic diversity. When computing inbreeding coefficients, you have to look at a deep pedigree to get accurate numbers. An inbreeding coefficient based on 10 generation pedigrees is standardly used, but requires a computerized pedigree database to compute.

The average inbreeding coefficient for a breed will be based on the age and genetic background of the breed. A mating with an inbreeding coefficient of 14 percent based on a ten generation pedigree, would be considered moderate inbreeding for a Labrador Retriever (a popular breed with a low average inbreeding coefficient), but would be considered outbred for an Irish Water Spaniel (a rare breed with a higher average inbreeding coefficient).

Most breeds start from a small founding population, and consequently have a high average inbreeding coefficient. If a breed is healthy and prolific, the breadth of the gene pool increases, and the average inbreeding coefficient can go down over time. Some dog breeds were established on a working phenotype, and not on appearance. These breeds usually start with low inbreeding coefficients due to the dissimilar backgrounds of the founders. As certain individuals are linebred on to create a uniform physical phenotype, the average inbreeding coefficient can increase.

There is no specific level or percentage of inbreeding that causes impaired health or vigor. If there is no diversity (non-variable gene pairs for a breed) but the homozygote is not detrimental, there is no effect on breed health. The characteristics that make a breed reproduce true to its standard are base on non-variable gene pairs. There are pure-bred populations where smaller litter sizes, shorter life expectancies, increased immune-mediated disease, and breed-related genetic disease are plaguing the population. In these instances, prolific ancestors have passed on detrimental recessive genes that have increased in frequency and homozygosity. With this type of documented inbreeding depression, it is possible that an outbreeding scheme could stabilize the population. However, it is also probable that the breed will not thrive without an influx of new genes; either from a distantly related (imported) population, or crossbreeding.

Fortunately, most breeds do not find themselves in the position of this amount of limited diversity and inbreeding depression. However, the perceived problem of a limited gene pool has caused some breeders to advocate outbreeding of all individuals. Studies in genetic conservation and rear breeds have shown that his practice contributes to the loss of genetic diversity. By uniformly crossing all “lines” in a breed, you eliminate the differences between them, and therefore the diversity between individuals. Eventually, there will not be any “unrelated line” to be found. Everyone will have a mixture of everyone else’s genes. The practice in livestock breeding has significantly reduced diversity, and caused the reduced diversity, loss of unique rare breeds.

A basic tenet of population genetics is that gene frequencies do not change from generation to generation. This will occur regardless of the homozygosity or heterozygosity of the parents, or whether the mating is an outbreeding, linebreeding, or inbreeding. This is the nature of genetic recombination. Selection, and not the types of matings used affect gene frequencies and breed genetic diversity.

If two parents are both heterozygous (both Aa) for a gene pair, on the average, they would produce 25% AA, 50% Aa, and 25% aa. (These are the averages when many litters are combined. In reality, any variety of pairing up can occur in a single litter.) If a prolific male comes out of this litter, and he is homozygous aa, then the frequency of the “a” gene will increase in the population, and the frequency of the “A” gene will decrease. This is known as the popular sire syndrome. Of course, each individual has thousands of genes that vary in the breed, and everyone carries some deleterious recessive genes. The overuse of individual breeding animals contributes the most to decreased diversity (population bottlenecks), and the increased spread of deleterious recessive genes (the founders effect). Again, it is selection (use of this stud to the exception of others), and not the types of matings he is involved in that alters gene frequencies. Breeders should select the best individuals from all lines, so as to not create new genetic bottlenecks.

Decisions to linebreed, inbreed or outbreed should be made based on the knowledge of an individuals traits and those of its ancestors. Inbreeding will quickly identify the good and bad recessive genes the parents share, based on their expression in the offspring. Unless you have prior knowledge of what the offspring of milder linebreedings on the common ancestors were like, you may be exposing your litters (and buyers) to extraordinary risk of genetic defects. In your matings, the inbreeding coefficient should only increase because you are specifically linebreeding (increasing the percentage of blood) to selected ancestors.

Don’t set too many goals in each generation, or your selective pressure for each goal will necessarily become weaker. Genetically complex or dominant traits should be addressed early in a long-range breeding plan, as they may take several generations to fix. Traits with major dominant genes become fixed more slowly, as the heterozygous (Aa) individuals in a breed will not be readily differentiated from the homozygous-dominate (AA) individuals. Desirable recessive traits can be fixed in one generation because individuals that show such characteristics are homozygous for the recessive genes. Individuals that pass on desirable traits for numerous matings and generations should be preferentially selected for breeding stock. This prepotency is due to homozygosity of dominate (AA) and recessive (aa) genes. However, these individuals should not be overused, to avoid the popular sire syndrome.

Breeders should plan their matings based on selecting toward a breed standard, based on the ideal temperament, performance, and conformation, and should select against the significant breed related health issues. Using progeny and sib-based information to select for desirable traits and against detrimental traits will allow greater control.

This article can be reproduced with the permission of the author. Jerold.Bell@tufts.edu


Food for thought… why can’t I get any puppies on the ground?

Photo by Silvia Timmermann

I was talking with another breeder this week about the “state” of Gordon Setter litters, the quantity of litters being produced as well as size of the litters surviving. The conversation centered around the observation that overall, the Gordon Setter breed appears to be experiencing a decrease in fertility as well as in the viability of newborn offspring. Fewer breedings are taking, fewer puppies are surviving. As breeders I believe we all (yes, I include myself) need to hold ourselves responsible for understanding what may be causing the creation of fertility issues and for the creation of their solution. It’s been said many times by numerous authors before me, when choosing a breeding pair we must consider the fertility and nurturing qualities of the sire and dam in addition to every other trait we consider desirable. To do that, breeders need to understand pedigrees and how they speak to us about the inbreeding coefficient of the litter –  as that coefficient my friends, can drive what is known as “inbreeding depression.” To eradicate inbreeding depression we first need to learn how to identify it and when it appears we need to acknowledge that this could be at play and then we need to plan our breeding accordingly.

I’m not a geneticist and I won’t ever pretend to be, luckily though I am a voracious reader, and with all of the information at our fingertips on the internet today I can find a wealth of expert information for my own, as well as your reading pleasure. I urge you to explore with me, if you’ve not already done so.

Photo by Silvia Timmerman

First let’s understand what’s meant by inbreeding. Inbreeding would be the breeding of related dogs who may be closely or distantly related to each other. Some, including me, designate inbreeding as close relationship breeding, like mother-son, father-daughter, sister-brother, and call “less close” breeding like a nephew-aunt breeding a line-breeding. But when reading articles written by the genetic expert you’ll find that it’s all packaged together under the name inbreeding. Don’t let that confuse you. With that said, if inbreeding is used carefully as part of a breeding plan that includes balancing the benefits with the dangers it can be a powerful tool. Using inbreeding without consideration of both positive and negative effects can be destructive.

Now let’s go back to inbreeding depression and talk about how that is related to the opening subject of decreased fertility in Gordon Setters and viability of newborn offspring. Inbreeding depression is not about an increase in the number of genetic disorders in the breed, like PRA for example. It refers to a loss of what a biologist would tell you is called fitness. Fitness in this context refers to the dog’s ability to pass on its genes to the next generation. So to a biologist, if a dog dies from disease before it can reproduce it has a fitness of zero. If a bitch successfully reproduces a litter but won’t properly care for her offspring (which will die without intervention) she has a fitness of zero. To breeders like us then, if our Gordon Setters have a high level of fitness they will produce offspring that can go on to reproduce themselves and perpetuate their genes in the population, where a Gordon Setter that cannot reproduce (without human intervention) or reproduces less effectively (below average litter size for example) have a low or zero fitness. In the Gordon Setter breed we could be experiencing evidence of inbreeding depression if we are in fact seeing an decrease in fertility and a decrease in litter viability. Evidence of inbreeding depression can be indicated by singleton litters, decline in conception rates, reduced sperm count, reduced litter size, lower pre and post-natal survival rates, shorter lifespans, higher cancer rates in young dogs, allergies, and many other issues that we might be taking for granted as normal in dog breeding these days. The “fitness” of the dog should be kept in mind as we make breeding choices.

My next step is to send you to some very informative articles I found at The Institute of Canine Biology (as I said earlier I am not a geneticist and won’t pretend that I can write in-depth articles about this topic). What a wonderful resource site!

Photo by Silvia Timmermann

(Quick note – the photos included in this article are simply for your viewing pleasure, they have nothing to do with the content of the article).

Now, “don’t go throwing the baby out with the bathwater” my friends – that’s not the message here. Oh,and don’t forget to pass it on! Your comments, questions and suggestions are always encouraged in our comment section.

Sally Gift, Mesa, AZ