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Pedigree Analysis, and How
Breeding Decisions Affect Genes
This article is
reprinted by permission of Dr. Jerold S Bell, DVM.
Tufts University School of Veterinary Medicine
Jerold.Bell@tufts.edu.
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. First comes understanding dogs and cats as
species, then as genetic individuals.
There is little similarity between a Chihuahua and a Saint Bernard,
or between a Himalayan and a Sphynx. However, we must understand
that while established breeds are separate entities among
themselves, they all are genetically the same species. While a
mating within a breed may be considered outbred, it still must be
viewed as part of the whole genetic picture: a mating within an
isolated, closely related, interbred population. Each breed was
developed by close breeding and inbreeding among a small group of
founding ancestors, either through a long period of genetic
selection or by intensely inbreeding a smaller number of
generations. This process established the breed's characteristics
and made the individuals in it breed true.
Pure-breeds have closed stud books. This means that the diversity
of genes in the breed is fixed. Genes cannot be gained through
breeding, only lost. In some cat breeds, cats who meet the
phenotypic standard of the breed may be introduced into the gene
pool. This, of course is an added source of genetic diversity for
the breed.
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 gene 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.
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 the
dissimilar traits of the parents. Such litters may be
phenotypically uniform, but will rarely breed true due to the 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 phenotypically
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 an 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 the 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 when 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 an outbred ancestor. If an ancestor is outbred and
generally heterozygous (Aa), increasing homozygosity will produce
more AA and aa. The way to reproduce an outbred ancestor is to mate
two individuals that mimic the appearance and pedigree of the
ancestor's parents.
Geneticists' and breeders' definitions of inbreeding vary. A
geneticist views inbreeding as a measurable number that goes up
whenever there is a common ancestor between the sire's and dam's
sides of the pedigree; a breeder considers inbreeding to be close
inbreeding, such as father‑to‑daughter or brother‑to‑sister matings.
A common ancestor, even in the eighth generation, will increase the
measurable amount of inbreeding in the pedigree.
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.
To visualize some of these concepts,
the pedigree of a Gordon Setter, Laurel Hill Braxfield Bilye will be
used. The paternal grandsire, CH Loch Adair Foxfire, and the
maternal grandam, CH Loch Adair Firefly WD, are full siblings,
making this a first‑cousin mating. The inbreeding coefficient for a
first cousin mating is 6.25%, which is considered a mild level of
inbreeding.
In Bilye’s pedigree, an inbreeding coefficient based on four
generations computes to 7.81%. This is not significantly different
from the estimate based on the first‑cousin mating alone.
Inbreeding coefficients based on increasing numbers of generations
are as follows: five generations, 13.34%; six generations, 18.19%;
seven generations, 22.78%; eight generations, 24.01%; ten
generations, 28.63%; and twelve generations, 30.81%. The inbreeding
coefficient of 30.81 percent is more than what you would find in a
parent‑to‑offspring mating (25%).
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 background inbreeding has far
more influence on the total inbreeding coefficient than the
first‑cousin mating, which only appears to be its strongest
influence.
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. It is a
measurement of the average percentage of genes the individual and
the ancestor should have in common.
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. This can occur in breeds, due either prolific
ancestors (usually males), or a small population of animals
originating the breed. Based on a twenty-five generation pedigree
of Bilye, there are only 852 unique ancestors who appear a total of
over twenty-million times.
In Bilye’s pedigree, CH Afternod Drambuie has the highest genetic
contribution of all of the linebred ancestors. He appears 33 times
between the sixth and eighth generations. One appearance in the
sixth generation contributes 1.56% of the genes to the pedigree.
His total contribution is 33.2% of Bilye’s genes, second only to the
parents. Therefore, in this pedigree, the most influential
ancestor doesn't even appear in a five-generation pedigree. His
dam, CH Afternod Sue, appears 61 times between the seventh and tenth
generations, and contributes more genes to the pedigree than a
grandparent.
Foundation dogs that formed the Gordon Setter breed also play a
great role in the genetic makeup of today’s dogs. Heather Grouse
appears over one million times between the sixteenth and
twenty-fifth generations, and almost doubles those appearances
beyond the twenty-fifth generation. He contributes over ten percent
of the genes to Bilye’s pedigree. This example shows that the depth
of the pedigree is very important in estimating the genetic makeup
of an individual. Any detrimental recessive genes carried by
Heather Grouse or other founding dogs, would be expected to be
widespread in the breed.
The average inbreeding coefficient of a breed is a measurement of
the breed’s 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).
Looking at the historical pedigrees of Bull Terrier breeding dogs
(males and females that have five or more registered offspring), we
find that for dogs born in the decade 1970-1979, the average ten
generation inbreeding coefficient was 23.11% +/- 6.04%. For Bull
Terriers born 1980-1989, this number is 21.54% +/- 5.69%. For
1990-1999, the average inbreeding coefficient is 19.01% +/- 6.23.
It is obvious that the 10 generation inbreeding coefficient of the
Bull Terrier breed is going down with each decade. This shows that
the breeders are utilizing the diversity of the gene pool, and not
breeding themselves into a corner with popular sires.
Of
course, the actual diversity of genes and inbreeding in the breed is
not going down It is just that the earlier ancestors producing
background inbreeding are falling beyond the 10th
generation, and are no longer included in the computation. As long
as the health and vitality of the breed is being maintained, and
there is no epidemic of breed-related disease from detrimental
recessives, this pure-bred population should be able to be
maintained.
Most breeds start from a small founding population, and consequently
have a high average inbreeding coefficient. If the 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 based 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, a
natural landrace 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 rare breeds have shown that this
practice actually 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.
This practice in livestock breeding has significantly reduced
diversity, and caused the loss of unique rare breeds.
A
fallacy of using outbreeding to maintain genetic diversity is the
belief that the diversity of a breed must be maintained in every
single animal. Breeders must concentrate on the specific goals of
breeding (selecting for the health and quality of the breed), versus
the tools used to get there (outbreeding, linebreeding, etc.)
Selecting breeding stock simply to produce the lowest possible
inbreeding coefficient is not a goal that will guarantee a quality
animal. Animals who are poor examples of the breed should not be
used simply to maintain diversity. Related individuals with
desirable qualities will maintain diversity, and improve the breed.
The process of maintaining healthy “lines” or families of animals,
with many breeders crossing between lines (outbreeding) and breeding
back (linebreeding) as they see fit maintains diversity in the gene
pool. It is the varied opinion of breeders as to what
constitutes the ideal representative of the breed, and their
selection of breeding stock that maintains breed diversity.
A basic tenet of population genetics
is that gene frequencies do not change from the parental generation
to the offspring. 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 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 individual's 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‑dominant (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
dominant (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.
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