Bull Terrier Genetics: Understanding Inheritance and Common Genetic Disorders

The Ins and Outs of Pedigree Analysis, Genetic Diversity,  and Genetic Disease Control 

Jerold S. Bell DVM, Dept. of Clinical Sciences, Cummings School of Veterinary Medicine,  Tufts University 

(This is an updated version of an article that originally appeared in the American Kennel Club  Gazette in September 1992 entitled, “Getting What You Want From Your Breeding Program.” It  is reprinted with the permission of Dr. Bell.) 

IT’S ALL IN THE GENES

As dog breeders, we engage in genetic "experiments" each time we plan a mating. The type of  mating selected should coincide with your goals. 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, we must understand how we manipulate genes within our breeding stock  to produce the kinds of dogs we want. We have to first understand dogs as a species, then dogs  as genetic individuals.  

The species, Canis familiaris, includes all breeds of the domestic dog. Although we can argue  that there is little similarity between a Chihuahua and a Saint Bernard, or that 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 canine ancestors,  either through a long period of genetic selection or by intensely inbreeding a smaller number of  generations. The process established the breed's characteristics and made the dogs in it breed  true.  

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 dog's ancestors, the better you can prioritize your  breeding goals. Tens of thousands of genes interact to produce a single dog. All genes are  inherited in pairs, one pair from the father and one from the mother. If the pair of inherited genes  from both parents is identical, the pair is called homozygous. If the genes in the pair are not  alike, the pair is called heterozygous. Fortunately, the gene pairs that make a dog a dog and not a  cat 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. 

BREEDING BY PEDIGREE

Outbreeding brings together two dogs less related than the average for the breed. This promotes  more heterozygosity, and gene diversity within each dog by matching pairs of unrelated genes  from different ancestors. Outbreeding can also mask the expression of recessive genes, and  allow their propagation in the carrier state. 

It is not unusual to produce an excellent quality dog from an outbred litter. The abundance of  genetic variability can place all the right pieces in one individual. Many top-winning show dogs  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 dogs related to their original stock, to increase homozygosity and  attempt to solidify newly acquired traits. 

Linebreeding attempts to concentrate the genes of a specific ancestor or ancestors through their  appearance multiple times in a pedigree.  The ancestor should appear behind more  than one offspring. If an ancestor always  appears behind the same offspring, you are  only linebreeding on the approximately 50  percent of the genes passed to the  offspring and not the ancestor itself. 

Increasing an individual's homozygosity through linebreeding may not, however, 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.  

PEDIGREE ANALYSIS

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. 

The inbreeding coefficient (or Wright’s coefficient) is an estimate of the percentage of all the  variable gene pairs that are homozygous due to inheritance from common ancestors. It is also the  average chance that any single gene pair is homozygous due to inheritance from a common ancestor. In order to determine whether a particular mating is an outbreeding or inbreeding  relative to your breed, you must determine the breed's average inbreeding coefficient. The  average inbreeding coefficient of a breed will vary depending on the breed's popularity or the age  of its breeding population. 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). 

For the calculated inbreeding coefficient of a pedigree to be accurate, it must be based on several  generations. Inbreeding in the fifth and later generations (background inbreeding) often has a  profound effect on the genetic makeup of the offspring represented by the pedigree. In studies  conducted on dog breeds, the difference in inbreeding coefficients based on four versus eight  generation pedigrees varied immensely. A four generation pedigree containing 28 unique  ancestors for 30 positions in the pedigree could generate a low inbreeding coefficient, while eight  generations of the same pedigree, which contained 212 unique ancestors out of 510 possible  positions, had a considerably higher inbreeding coefficient. What seemed like an outbred mix of  genes in a couple of generations, appeared as a linebred concentration of genes from influential  ancestors in extended generations. 

The process of calculating coefficients is too complex to present here. Several books that include  how to compute coefficients are indicated at the end of this article; some computerized canine  pedigree programs also compute coefficients. The analyses in this article were performed using  CompuPed, by MBF Software. 

Pedigree of Gordon Setter Laurel Hill Braxfield Bilye 

( a spayed female owned by Dr. Jerold and Mrs. Candice Bell, and co-bred by Mary Poos and Laura Bedford.)

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%). As you can see, 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 percent blood coefficient measures the  relatedness between an ancestor and the individual represented by the pedigree. It estimates the  probable percentage of genes passed down from a common 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. This can occur in breeds, due either prolific ancestors (usually stud dogs), or a small  population of dogs 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. 

Pedigree Analysis of Laurel Hill Braxfield Bilye

(computed to 25 generations) 

1st Generation
Linebred Ancestors	Percentage of Blood	of appearance in pedigree	# times in pedigree
CH Afternod Drambuie	33.20%	6	33
CH Afternod Sue	27.05%	7	61
CH Afternod Callant	26.56%	5	13
“Grand-Parents”	25.00%	2	1
CH Sutherland Gallant	25.00%	3	2
CH Sutherland MacDuff	25.00%	3	3
CH Sutherland Lass of Shambray	25.00%	3	2
CH Wilson's Corrie, C.D.	22.30%	7	200
CH Afternod Buchanon	20.22%	7	48
Loch Adair Diana of Redchico	17.97%	5	12
CH EEG’s Scotia Nodrog Rettes	17.76%	8	181
Afternod Ember of Gordon Hill	17.14%	8	76
CH Afternod Hickory	16.21%	6	27
CH Black Rogue of Serlway	15.72%	9	480
CH Afternod Woodbine	14.45%	6	15
CH Fast’s Falcon of Windy Hill	13.82%	8	66
Afternod Fidemac	13.67%	5	7
CH Page’s MacDonegal II	13.43%	7	56
Afternod Hedera	13.38%	7	56
CH Downside Bonnie of Serlway	12.90%	10	708
Peter of Crombie	12.76%	11	3,887
“Great-Grand-Parents”	12.50%	3	1
CH Afternod Amber	12.50%	5	5
Ben of Crombie	11.83%	11	7,584
Stylish William	11.18%	13	23,764
Stylish Billie	11.08%	14	70,542
Stylish Ranger	10.80%	15	297,331
CH Afternod Kate	10.74%	6	17
Heather Grouse	10.61%	16	1,129,656
Afternod Hedemac	10.45%	7	28

The above analysis shows the ancestral contribution of the linebred ancestors in Bilye’s pedigree.  Those dogs in color were present in the five-generation 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  the 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. 

BREEDING BY APPEARANCE

Many breeders plan matings solely on the appearance of a dog and not on its pedigree or the  relatedness of the prospective parents. This is called assortative mating. Breeders use positive  assortative matings (like-to-like) to solidify traits, and negative assortative matings  (like-to-unlike) when they wish to correct traits or bring in traits their breeding stock may lack. 

Some individuals may share desirable characteristics, but they inherit them differently. This is  especially true of polygenic traits, such as ear set, bite, or length of forearm. Breeding two  phenotypically similar but genotypically unrelated dogs together would not necessarily reproduce  these traits. Conversely, each individual with the same pedigree will not necessarily look or  breed alike. 

Breedings should not be planned solely on the basis of the pedigree or appearance alone.  Matings should be based on a combination of appearance and ancestry. If you are trying to  solidify a certain trait - like topline - and it is one you can observe in the parents and the linebred  ancestors of two related dogs, then you can be more confident that you will attain your goal. 

GENETIC DIVERSITY 

Some breed clubs advocate codes of ethics that discourage linebreeding or inbreeding, as an  attempt to increase breed genetic diversityThe types of matings utilized do not cause the loss  of genes from a breed gene pool. It occurs through selection; the use and non-use of offspring. If some breeders linebreed to certain dogs that they favor, and others linebreed  to other dogs that they favor, then breed-wide genetic diversity is maintained.  

In a theoretical mating with four offspring, we are dealing with four gene pairs. The sire is  homozygous at 50% of his gene pairs (two out of four), while the dam is homozygous at 75% of  her gene pairs. It is reasonable to assume that she is more inbred than the sire. 

Dogs who are poor examples of the breed should not be used simply to maintain diversity.  Related dogs with desirable qualities will maintain diversity, and improve the breed. Breeders  should concentrate 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 against both polygenic disorders and  those without a known mode of inheritance will allow greater control.  

Rare breeds with small gene pools have concerns about genetic diversity. What constitutes  acceptable diversity versus too restricted diversity? The problems with genetic diversity in  purebred populations concern the fixing of deleterious recessive genes, which when homozygous  cause impaired health. Lethal recessives place a drain on the gene pool either prenatally, or  before reproductive age. They can manifest themselves through smaller litter size, or neonatal  death. Other deleterious recessives cause disease, while not affecting reproduction. 

Problems with a lack of genetic diversity arise at the gene locus level. There is no specific level  or percentage of inbreeding that causes impaired health or vigor. It has been shown that some  inbred strains of animals thrive generation after generation, while others fail to thrive. 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. A genetic health problem arises for a breed when a detrimental  allele increases in frequency and homozygosity. 

GENETIC CONSERVATION

The perceived problem of a limited gene pool has caused some breeds to advocate outbreeding of  all dogs. 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. This  practice in livestock breeding has significantly reduced diversity, and caused the loss of unique  rare breeds. The process of maintaining healthy “lines” or families of dogs, with many breeders  crossing between lines and breeding back as they see fit maintains diversity in the gene pool. It  is the varied opinion of breeders as to what constitutes the ideal dog, and their selection of  breeding stock that maintains breed diversity.  

The Doberman Pincher breed is large, and genetically diverse. The breed has a problem with von  Willibrand’s disease, an autosomal recessive bleeding disorder. Based on genetic testing, the  frequency of the defective gene is 52.5% (23% normal, 49% carriers and 28% affected).  Doberman Pincher breeders can identify carrier and affected dogs, and decrease the defective  gene frequency through selection of normal-testing offspring for breeding. By not just  eliminating carriers, but replacing them with normal-testing offspring, genetic diversity will be  conserved. 

Dalmatians have a defective autosomal recessive purine metabolism gene that can cause urate  bladder stones and crystals, and/or a skin disorder called Dalmatian Bronzing Syndrome. All  Dalmatians are homozygous recessive for the defective gene. At one time, the breed and the  AKC approved a crossbreeding program to a single Pointer, to bring the normal-purine  metabolism genes into the gene pool. The program was abandoned by the National club for  several reasons including; concern about the impact of other Pointer genes foreign to the  Dalmatian gene pool, and unacceptable spotting patterns in the crossbreds. The crossbreeding  program continued, and greater than twelve generations from pure Pointer influence is producing  properly spotted, normal-purine Dalmatians. Now that the AKC allows these dogs into the gene  pool, the breed will have to be concerned about popular sire effects and limited diversity from  using the normal-purine dogs too extensively. 

The Akita has several breed-related autoimmune disorders that although infrequent, occur at  frequencies greater than other breeds. These include uveodermatological syndrome, pemphigus,  sebaceous adenitis, juvenile arthritis, myasthenia gravis, and autoimmune thyroiditis. Research  has shown that there is a lack of diversity at a major histocompatability gene in the breed, with a  single allele occurring at a very high frequency. The major histocompatability complex is  integral to a properly functioning immune system. The relationship of this lack of diversity to  autoimmunity is being studied. 

PUTTING IT ALL TOGETHER 

Decisions to linebreed, inbreed or outbreed should be made based on the knowledge of an  individual dog's traits and those of its ancestors. Inbreeding will quickly identify the good and  bad recessive genes the parents share in the offspring. Unless you have prior knowledge of what  the pups of milder linebreedings on the common ancestors were like, you may be exposing your  puppies (and puppy 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. Dogs that breed true 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. 

If you linebreed and are not happy with what you have produced, breeding to a less related line  immediately creates an outbred line and brings in new traits. Repeated outbreeding to attempt  to dilute detrimental recessive genes is not a desirable method of genetic disease control.  Recessive genes cannot be diluted; they are either present or not. Outbreeding carriers  multiples and further spreads the defective gene(s) in the gene pool. If a dog is a known carrier  or has high carrier risk through pedigree analysis, it can be retired from breeding, and replaced  with one or two quality offspring. Those offspring should be bred, and replaced with quality  offspring of their own, with the hope of losing the defective gene. 

Trying to develop your breeding program scientifically can be an arduous, but rewarding,  endeavor. By taking the time to understand the types of breeding schemes available, you can  concentrate on your goals towards producing a better dog. 

This article can be reprinted with the permission of Dr. Bell (jerold.bell@tufts.edu)

Pedigree Analysis and How Breeding Decisions Affect Genes  

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. 

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 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. 

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.

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.  

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  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, 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 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 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. 

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

The Effects of Genetic Testing: Constructive or Destructive?

By Jerold S. Bell, DVM, Tufts Cummings School of Veterinary Medicine(This article originally appeared in the June, 2001 issue of the AKC Gazette)

Every breed has genetic disorders. Finding tests that identify carriers of the genes which cause these disorders is a goal in all breeds. Once a genetic test is found, however, it is a double-edged sword: Its use can enable breeders to improve a breed or devastate it.

Without genetic tests, the number of dogs that can be identified as carriers is low, even though many dogs may be suspected of being carriers because they have relatives that are known to be affected. Without tests, though, genetic-disease control involves breeding higher-risk dogs to lower-risk dogs. Dog breeds have closed gene pools; in other words, the diversity of genes in a given breed is fixed. The number of dogs removed from consideration for breeding based on concerns regarding a specific genetic disease is usually low, and therefore does not greatly alter the breed’s gene pool, or diversity. A genetic test that should be used to help maintain breed diversity should not result in limiting it.

However, once a genetic test is developed that allows breeders to positively determine if a dog is a carrier of a defective gene, many owners are likely to remove carrier dogs from their breeding stock. Although doing so is human nature, this temptation must be overcome. Any quality dog that you would have bred if it had tested normal should still be bred if it tests as a carrier.

Any quality dog that you would have bred if it had tested normal should still be bred if it tests as a carrier. 

In such circumstances, carriers should be bred to normal-testing dogs. This ensures that affected offspring will not be produced. Carrier breeding stock should be subsequently replaced with normal-testing offspring that exceeds it in quality. If the only quality offspring is also a carrier, then use that offspring to replace your original carrier. You have improved the quality of your breeding stock, even though the defective gene remains in this generation. It is certainly true, though, that the health of the breed does depend on diminishing the carrier frequency and not increasing it. You should therefore limit the number of carrier-testing offspring that you place in breeding homes. This does not mean, however, that you should prevent all of them from being bred. It is important to carry on lines. A genetic test that should be used to help maintain breed diversity should not result in limiting it. 

Consider All Aspects 

We know that most dogs carry some unfavorable recessive genes. The more genetic tests that are developed, the greater chance there is of identifying an undesirable gene in your dog. Remember, however, that your dog is not a single gene, an eye, a hip, or a heart. Your dog carries tens of thousands of genes, and each dog is a part of the breed's gene pool. When considering a breeding, you must consider all aspects of the dog - such as health issues, conformation, temperament and performance - and weigh the pros and cons. When a good-quality dog is found to carry a testable defective gene, there is a better option than removing that dog from your breeding program. That option is to breed it, so that you can keep its good qualities in the gene pool, and then replace it in your program with a normal-testing dog.

There are breeders who contend that no more than 10 percent of carrier dogs should be removed from breeding in each generation. Otherwise, they say, the net loss to the gene pool would be too great. In fact, less than 10 percent of all dogs in a breed are ever used for breeding. Dog breeds do not propagate according to what is known as the Hardy-Weinberg equilibrium, where all members of a group reproduce and pass on their genes to the next generation. Breeders already place tremendous pressure on their gene pools through selective breeding decisions. Indeed, breeders who focus their selective pressure on the more elusive traits in their dogs, rather than on testable and predictable single-gene conditions, are right to do so.

The Dangers  

It is important that breed clubs educate their owners on how genetic tests should be properly interpreted and used. History has shown that breeders can be successful in reducing breed- wide genetic disease through testing and making informed breeding choices. You should remember, however, that there are also examples of breeds that have actually experienced more problems as a result of unwarranted culling and restriction of their gene pools.

These problems include: reducing the incidence of one disease and increasing the incidence of another by repeated use of stud dogs known to be clear of the gene that causes the first condition; creating bottlenecks and diminishing diversity by eliminating all carriers of a gene from the pool, instead of breeding and replacing them; and concentrating on the presence or absence of a single gene and not the quality of the whole dog.

Breeders are the custodians of their breed's past and future. "Above all, do no harm" is a primary oath of all medical professionals. Genetic tests are powerful tools, and their use can cause significant positive or negative changes. Breeders should be counseled on how to utilize test results for the best interests of the breed.

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

Removing the stigma of genetic disease 

Jerold S Bell, DVM 

Tufts Cummings School of Veterinary Medicine, N. Grafton, MA (Adapted from an article published in the “Healthy Dog” section of the October, 2003 AKC Gazette) 

An inevitable consequence of breeding is the  occurrence of genetic problems. No one  wants to produce affected dogs, yet some  breeders and owners are quick to assign  blame. There are no perfect dogs, and all  dogs carry some detrimental genes. 

Reducing the stigma of  genetic disease involves  raising the level of  conversation from gossip to  constructive communication.  Dealing with genetic  disorders is a community  effort. 

The emotional reaction  to producing a dog with  a genetic disorder often follows what is called  the grief cycle: 

* Denial: This isn’t  genetic. It was caused by  something else. 

* Anger: This isn’t right! Why is this  happening to my dogs?  

* Bargaining: My dog sired more than 100  other dogs that are healthy. So this one  doesn’t really count, right? 

* Depression: My kennel name is ruined. No one will breed to my dogs. 

* And, finally, acceptance: My dog was  dealt a bad genetic hand.  

There are ways to manage genetic disorders,  breed away from this, and work toward a  healthier breed. 

Getting beyond denial 

Unfortunately, many breeders can’t get  beyond the denial stage. Some will hold to  increasingly improbable excuses, rather than  accept that a condition is genetic. They will  falsely blame relatively rare disorders on  common viruses, bacteria, or medications.  The fact that these organisms or drugs are  common to millions of dogs annually who do not have these disorders is not  considered. 

Some owners state that their veterinarian  recommended not sending in a hip  radiograph to the Orthopedic Foundation for  Animals (OFA) because the dog would  probably be diagnosed with hip dysplasia. Then these owners lull themselves into believing that since the dog wasn’t evaluated, it does not have hip dysplasia. The fact that a dog does not have an official diagnosis does not mean the dog has normal hips, “not affected” with hip dysplasia.

It is important to confirm diagnoses of  genetic disorders with blood tests,  radiographs, or pathology specimens.  However, the primary concern should  always be for the individual dog. If an  affected dog is not suffering, it should not be  euthanized simply to obtain a pathological  diagnosis. The increased availability of non non- invasive techniques has made diagnoses easier to obtain.

Once confirmation of a genetic disorder is  made, denial sometimes becomes deception,  which is not acceptable. There are breeders who actively seek to prevent diagnoses and  later necropsies, but who eventually realize  those actions are detrimental to the breed, and in the long run to themselves. 

Working together to improve our breeds Reducing the stigma of genetic disease  involves raising the level of conversation  from gossip to constructive communication.  Dealing with genetic disorders is a community effort. Each breeder and owner will have a different level of risk or involvement for a disorder. We do not get to choose the problems with which we have to deal. Breeders should be supportive of others who are making a conscientious effort to continue breeding their dogs while decreasing the risk of passing on defective genes.

Breeders should follow up on the puppies  they have placed. Breeders should periodically contact their puppy buyers and  ask about the health of the dogs. Some  breeders fear they will be castigated if a dog  they placed develops a problem. However,  the vast majority of owners of affected dogs  are pleased that their breeder is interested in  their dog, and in improving the health of the  breed so that other affected dogs are not  produced. 

A breeder cannot predict or prevent every  health problem. If an owner’s dog is  discovered to have a problem, show your  concern. 

Breeders and breed clubs should be  cooperative and supportive of researchers  studying genetic disorders in their breed.  Through research funded by breed clubs and  by the AKC Canine Health Foundation  (CHF), new genetic tests for carriers of  defective genes are continually being developed. 

The Canine Health Information Center  (CHIC; www.caninehealthinfo.org) was established by the CHF and the Orthopedic  Foundation for Animals (www.offa.org). CHIC is an online registry that works with  the breed parent clubs to establish a panel of  testable genetic disorders that should be  screened for in each breed. The beauty of  the CHIC concept is that dogs achieve CHIC  certification by completing the health-checks. Passing each health test is not a requirement for certification. CHIC is about being health conscious, not about being faultless. 

My hope for each breed is that there will  eventually be so many tests for defective  genes that it will not be possible for any dog  to be considered “perfect.” Then we can put  emotions aside and all work together on  improving our breeds. 

Breeders must lead the way to remove the  stigma of genetic disorders. The  applications for both the OFA and CHIC  health registries include options that allow  for open disclosure of all health-test results  or semi-open disclosure listing only normal  results. It is up to breeders to show that they are ready to move genetic disorders out of  the shadows and check off the boxes for full  disclosure. 

More and more national clubs are having  health seminars and health screening clinics  at their specialties. This shows those breed  clubs and breeders care about the genetic  health of their breeds, and are working  toward a healthier future. 

This article can be reprinted with the  permission of the author:  jerold.bell@tufts.edu

Breeding Strategies for Managing Genetic Traits  

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

With each new generation of dogs, breeders ask,  “How can I continue my line and improve it?”  Aside from selecting for conformation, behavior  and ability, breeders must consider how they are  going to reduce the incidence of whichever  genetic disorders are present in their breed. There  are no answers that will fit every situation. There  are, however, guidelines you can follow to  preserve breeding lines and genetic diversity  while reducing the risk of producing dogs that  carry defective genes, or are affected with genetic  defects.  

Autosomal Recessive Disorders  

In the case of a simple autosomal recessive  disorder for which a test for carriers is available,  the recommendation is to test your breeding quality stock, and breed carriers to normal-testing  dogs. The aim is to replace the carrier breeding animal with a normal-testing offspring that equals  or exceeds it in quality. You don’t want to  diminish breed diversity by eliminating quality  dogs from the gene pool because they are carriers.  As each breeder tests and replaces carrier dogs  with normal-testing dogs, the problem for the  breed as a whole diminishes.  

For some disorders there are tests known as  linkage-based carrier tests, which can generate a  small percentage of false positive and negative  results. When using these tests to make breeding  decisions, it’s advisable to first determine whether  the results correlate with the test results and  known genotypes of relatives.  

When dealing with a simple autosomal recessive  disorder for which no carrier test exists, breeders  must assess whether each individual dog in their  breeding program is at high risk of being a carrier.  This requires knowledge of the carrier or affected  status of close relatives in the pedigree. An open  health registry that is supported by the parent club  makes it easier for breeders to objectively assess  these matters. By determining the average carrier-risk for the breeding population, breeders  can select matings that have a projected risk  which is lower than the breed average.   

If breeding a dog that is at high risk of being a  carrier, the best advice is to breed to a dog that  has a low risk. This will significantly diminish  the likelihood that affected dogs will be  produced, and can reduce by up to half the risk  that there will be carriers among the offspring.  Using relative-risk assessment as a tool, breeders  should replace higher-risk breeding dogs with  lower-risk offspring that are equal to or better  than their parents in quality. Relative-risk  assessment allows for the continuation of lines  that might otherwise be abandoned due to high  carrier risk.  

Breeding a dog only once and replacing it with  an offspring allows breeders to improve their  chances of moving away from defective genes  and also limits the dissemination of defective  genes. When dealing with disorders for which  carriers cannot be identified, the number of  offspring placed in breeding homes should be  kept to a minimum. 

Autosomal Dominant Disorders  

Autosomal dominant genetic disorders are  usually easy to manage. Each affected dog has at  least one affected parent, but it can be expected  that half of the offspring of an affected dog will  be free of the defective gene. With disorders that  cause death or discomfort, the recommendation  is to not breed affected dogs. To produce the  next generation of a line, a normal full sibling of  an affected dog can be used, or the parent that is  normal can be used.  

A problem with some autosomal dominant  disorders is incomplete penetrance. In other  words, some dogs with the defective gene may  not show the disorder. Roughly half their  offspring, however, may be affected. If a genetic test is available, this is not a problem. Otherwise,  relative-risk assessment can identify which dogs  are at risk of carrying incompletely penetrant  dominant genes.  

Sex-Linked Disorders  

For sex-linked (also known as x-linked) recessive  defective genes for which carrier tests exist,  breeders should follow the same “breed and  replace” recommendations as are outlined above  in the discussion of autosomal recessive disorders.  If there is no test, the defective gene can be traced  through the pedigree. If a male is affected, he  would have received the defective gene from his  carrier mother. All of his daughters will be  carriers, but none of his sons. By using relative risk assessment to breed him to a female that is at  low risk of being a carrier, you can prevent  affected offspring, and select a quality son for  replacement.  

There are rare instances in which a female is  affected with a sex-linked disorder. In such cases,  she would have received the defective gene from  both parents; specifically, an affected father and a  mother who is either a carrier or is affected  herself. If an affected female is bred, all the sons  will be affected, and all the daughters would be  carriers, so affected females clearly should not be  bred. A normal male that is a littermate to an  affected female, however, would be able to carry  on the line without propagating the defective  gene.  

Sex-linked dominant disorders are managed the  same way as autosomal dominant disorders are.  The difference is that affected males willalways produce all affected daughters.

Polygenic disorders  

Polygenic disorders are those caused by more  than one pair of genes. Most polygenic disorders  have no tests for carriers, but they do have  phenotypic tests that can identify affected dogs. With polygenic disorders, a number of genes  must combine to cross a threshold and produce  an affected dog. These are known as liability  genes. In identifying a dog’s liability for  carrying defective genes for a polygenic  disorder, the breadth of the pedigree (that is,  consideration of all siblings of individuals in the  pedigree) is more important than the depth of the  pedigree (consideration only of parent-offspring  relationships.) A clinically normal dog from a  litter that had one or no individuals affected with  hip dysplasia (which is a polygenic disorder) is  expected to carry a lower amount of liability  genes than a dog with a greater number of  affected littermates. This is why it is important  to screen both pet and breeding dogs from your  litters for polygenic disorders. Information on  the siblings of the parents of potential breeding  dogs provides additional data on which to base  your breeding decisions.  

Genetic disorders without a known mode of  inheritance should be managed in the same way  as polygenic disorders. If there are multiple  generations of normalcy in the breadth of the  pedigree, then you can have some confidence  that there are less liability genes being carried. If  a dog is diagnosed with a genetic disorder, it can  be replaced with a normal sibling or parent and  bred to a mate whose risk of having liability  genes is low. Replace the higher-risk parent with  a lower-risk offspring that equals or exceeds it in  other aspects, and repeat the process.  

Genetic tests are extremely useful tools to help  manage genetic disorders. Even when there is no  test, or a known mode of inheritance, much can  still be done to reduce the incidence of affected  and carrier animals. The use of these guidelines  can assist breeders in making objective breeding  decisions for genetic-disease management, while  continuing their breeding lines.

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

Popular-Sire Syndrome: Keeping watch over health and quality issues in purebreds 

By Jerold S Bell, DVM, Tufts Cummings School of Veterinary Medicine 
(This article originally appeared in the “Healthy Dog” section of the August, 2004 AKC Gazette)  

An important issue in dog breeding is the  popular-sire syndrome. This occurs when  a stud dog is used extensively for  breeding, spreading his genes quickly  throughout the gene pool. There are two  problems caused by the popular-sire  syndrome. One is that any detrimental  genes which the sire carries will  significantly increase in frequency –  possibly establishing new breed-related  genetic disorders.  Second, as there are  only a certain  number of bitches  bred each year,  overuse of a popular sire excludes the use of other quality  males, thus narrowing the diversity of the  gene pool. 

The problem with the popular-sire syndrome  is that the dog’s genes are spread widely and  quickly - without evaluation of the long term effects of his genetic contribution. By  the time the dog’s genetic attributes can be  evaluated through  

The popular-sire syndrome is not limited  to breeds with small populations. Some  of the most populous breeds have had  problems with this syndrome.  Compounding this, there are several  instances where a popular sire is replaced  with a son, and even later a grandson.  This creates a genetic bottleneck in the  breeding population, narrowing the  variety of genes available.  

Every breed has its prominent dogs in the  genetic background of the breed. But  most of these dogs become influential  based on several significant offspring that  spread different combinations of the  dog’s genes over several generations.  The desirable and undesirable  characteristics of the dog were passed on,  expressed, evaluated by breeders, and determined if they were worthy of  continuing in future generations.  

The Challenges  

The problem with the popular sire syndrome is that the dog’s genes are spread widely and quickly - without evaluation of the long-term effects of his genetic contribution. By the time the dog’s genetic attributes can be evaluated through offspring and grand-offspring, his genes have already been distributed widely, and his effect on the gene pool may not be easily changed.

In almost all instances, popular sires are  show dogs. They obviously have  phenotypic qualities that are desirable, and  as everyone sees these winning dogs, they  are considered desirable mates for breeding.  What breeders and especially stud-dog  owners must consider is the effect of their  mating selection on the gene pool. At what  point does the cumulative genetic  contribution of a stud dog outweigh its  positive attributes? A popular sire may only  produce a small proportion of the total  number of litters registered. However, if the  litters are all out of top-quality, winning  bitches, then his influence and the loss of  influence of other quality males may have a  significant narrowing effect on the gene  pool.

In some European countries, dog-breeding  legislation is being considered that limits the  lifetime number of litters a dog can sire or  produce. If, however, certain matings  produce only pet-quality dogs, but no  quality breeding prospects, should the  dog be restricted from siring a litter from  a different line? The popular sire’s effect  on the gene pool is on the number of  offspring that are used for breeding in the  next generation, and how extensively  they are being used. This cannot be  legislated.  

At what point does a stud-dog owner  determine that their dog has been bred  enough? It can be difficult to deny stud  service when asked, but the genetic effect  of a dog on the whole breed must be  considered. If everyone is breeding to a  certain stud dog, the intelligent decision  may be to wait and see what is produced  from these matings. If you still desire  what the stud dog produces, it is possible  that you can find an offspring who has  those positive attributes, and also a  genetic contribution from its dam that  you may find desirable. If a popular stud  dog deserves to make a significant  genetic contribution to the breed, doing  so through multiple offspring, and  therefore getting a mixed compliment of  his genes, is better than focusing on a  single offspring.  

Wait-and-See Approach  

All breeding dogs should be health tested  for the conditions seen in the breed. If  your breed has enrolled in the AKC Canine Health Foundation/Orthopedic  Foundation for Animals CHIC program  (www.caninehealthinfo.org), prospective  breeding dogs and bitches should   complete the recommended breed specific health testing prior to breeding.  These may include hip radiographs,  CERF eye examinations, or specific  genetic tests.  

It is important to monitor the positive and  negative characteristics being produced by  popular sires. While it is satisfying to own a  popular stud dog, a true measure of a  breeder’s dedication is how negative health  information in the offspring is made  available. All dogs carry some undesirable  traits. Based on the variety of pedigree  background of bitches who are usually  brought to popular sires, there is a greater  chance that some undesirable traits could be  expressed in the offspring. It is up to the  stud-dog owner to keep in touch with bitch  owners, and check on the characteristics that  are being produced.  

Some breeders will argue that the strength of  a breed is in its bitches, but the fact remains  that the stud dogs potentially have the  greatest cumulative influence on the gene  pool. There will always be popular sires,  and that is not necessarily bad for a breed.  But a dog’s influence on a breed should be  gradual, and based on proven production  and health testing. Maintaining surveillance  of health and quality issues in breeding dogs  and their offspring, and preserving the  genetic diversity of the gene pool, should  allow a sound future for purebred dogs.  

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

Small Population Breeds and Issues of Genetic Diversity

Jerold S Bell DVM, Adjunct Professor of Genetics, Cummings School of Veterinary Medicine at Tufts  University 

(This article was originally published in the March 2007 AKC Perspectives Delegates Newsletter.)  

Issues of genetic diversity are a concern to dog breeders, and this can especially be so for  breeds with small populations. The concern is whether there is enough genetic variation  within a breed’s gene pool to maintain health and vitality. Breeders should be concerned  about genetic diversity, because there are examples where damage has been done to a  breed due to breeding practices. Restriction of genetic diversity can also occur in large  population breeds. 

All genes come in pairs: one from the sire and one from the dam. Each gene in the pair is  called an allele. If both alleles in a pair are of the same type, the gene pair is  homozygous. If the two alleles are different, the gene pair is heterozygous. While each  dog can have a maximum of two different alleles at a gene pair, many different alleles are  potentially available to be part of the gene pair. The greater the number of alleles that are  available at each gene pair (called genetic polymorphism), the greater the genetic  diversity of the breed. 

If there is no breed diversity in a gene pair, but the particular homozygous gene that is  present is not detrimental, there is no negative effect on breed health. The characteristics  that make a breed reproduce true to its standard are, in fact, based on nonvariable (that is,  homozygous) gene pairs. 

The origins of breeds have a lot to do with genetic diversity. A breed established with a  working phenotype tends to have diverse founder origins, and significant diversity. Even  with substantial population bottlenecks, the breed can maintain considerable amounts of  genetic diversity. This was shown in a molecular genetic study of the Chinook breed,  which was reduced to 11 modern founders in 1981. Breeds established by inbreeding on  a limited number of related founder individuals could have reduced diversity. Many  breeds have also gone through diversity reducing bottlenecks; such as occurred during  World War II. For most of these breeds, their gene pools have expanded through  breeding for many generations, resulting in a stable population of healthy dogs. 

There are two factors that must be considered when evaluating genetic diversity and  health issues in a breed; the average level of inbreeding, and detrimental recessive genes.  With a small population, there is a tendency to find higher average inbreeding  coefficients due to the relatedness between dogs from common ancestors. There is,  however, no specific level or percentage of inbreeding that causes impaired health or  vigor. The problems that inbreeding depression cause in purebred populations stem from  the effects of deleterious recessive genes. If the founding population of a breed produces  a high frequency of a deleterious recessive gene, then the breed will have issues with that  disorder. This can be seen as smaller litter size, increased neonatal death, high frequency  genetic disease, or impaired immunity. If these issues are present then the breed needs to  seriously consider limited genetic diversity.

The issue of high average inbreeding coefficients is one that all breeds go through during  their foundation. As the population increases and the average relatedness of dogs goes  down (based on a fixed number of generations), the average inbreeding coefficient for the  breed will go down. The effect of initially higher inbreeding coefficients in small  population breeds will depend on the presence of deleterious recessive genes that will be  expressed when homozygous. 

Some breeders discourage linebreeding and promote outbreeding in an attempt to protect  genetic diversity in their breed. It is not the type of matings utilized (linebreeding or  outbreeding) that causes the loss of genes from a breed gene pool. Rather, loss of genes  occurs through selection: the use and non-use of offspring. If a breed starts narrowing  their focus to breeding stock from a limited number of lines, then a loss of genetic  diversity will occur. 

The process of maintaining healthy lines, with many breeders crossing between lines and  breeding back as they see fit, maintains diversity in the gene pool. If some breeders  outbreed, and some linebreed to certain dogs that they favor while others linebreed to  other dogs that they favor, then breedwide genetic diversity is maintained. It is the varied  opinion of breeders as to what constitutes the ideal dog, and their selection of breeding  stock based on their opinions, that maintains breed diversity. 

The most important factor for diminished genetic diversity in dog breeds is the popular  sire syndrome. The overuse of a popular sire beyond a reasonable contribution through  frequent breedings significantly skews the gene pool in his direction, and reduces the  diversity of the gene pool. Any genes that he possesses - whether positive or negative - will increase in frequency. Through this founder’s effect, breed-related genetic disease  can occur. Another insidious effect of the popular sire syndrome is the loss of genetic  contribution from quality, unrelated males who are not used for breeding. There is a  finite number of quality bitches bred each year. If one male is used in an inordinate  amount of matings, there will be fewer females left for these quality males that should be  contributing to the gene pool. The popular sire syndrome is a significant factor in both  populous breeds and breeds with small populations. 

The best methods for ensuring the health and diversity of any breed’s gene pool are to: 1)  Avoid the popular sire syndrome. 2) Utilize quality dogs from the breadth of your  population to expand the gene pool. 3) Monitor genetic health issues through regular  health surveys. 4) Do genetic testing for breed-related disorders. 5) Participate in open  health registries, such as CHIC (www.caninehealthinfo.org) to manage genetic disorders. 

This article can be reprinted with the written permission from the author:  jerold.bell@tufts.edu

UNDERSTANDING BREEDS AS POPULATIONS 

Jerold S Bell DVM jerold.bell@tufts.edu Cummings School of Veterinary Medicine at Tufts University 

This article was presented at the 2019 AKC Canine Health Foundation National Parent Club Canine Health  Conference. It can be reprinted with the written permission of the author 

Dog breeds are like different ethnic populations of people. All people on earth are humans (Homo  sapiens), but we are not all closely related. Ethnic populations originally arose due to geographic  isolation. There are some mutated genes (and hereditary diseases) that are shared by different ethnic  populations. These mutations occurred a long time ago in distant ancestors that preceded population  migrations and the separation of ethnic populations. In some ethnic populations certain common  genetic diseases occur at a higher frequency (like high blood pressure and diabetes). Some ethnic  populations are prone to certain genetic diseases that are seen very rarely in other populations.  

The same thing occurs in purebred dog populations. Dog breed populations are like early isolated  human populations. The most common genetic diseases that are seen by veterinarians every day in  practice are due to ancient liability genes that originated in ancestors that preceded the separation of  breeds. They occur in both purebred and mixed breed dogs. These include allergies, hip dysplasia, heart  disease, cruciate ligament disease, slipping kneecaps, cataracts, hereditary cancers and others. Breed specific genetic disorders are due to more recent mutations. For many genetic disorders, validated  genetic tests are available to identify carriers. For others, genetic screening and medical history  differentiate normal from affected dogs. 

BREED FORMATION & CHROMOSOMAL INHERITANCE 

Breeds were formed by selecting for a working, behavioral and/or conformational standard. Dogs that  did not adhere to a standard or were unhealthy were discarded. Those that did adhere were used for  breeding. As only a small number of dogs are used to produce the next generation, rapid change can  occur in the breed's genetic background. Dogs that embody and produce health and quality were considered superior to the standard and their offspring were used more frequently. Their genes were  retained and propagated in the breed gene pool. Dogs that produced offspring that were unhealthy or  inferior to a standard were not used. Their influence and that of their ancestors was diminished. 

Dogs have 39 pairs of chromosomes – one in each pair from its sire and one from its dam. Dogs used for  breeding supply one chromosome from each pair to every offspring. Due to chromosomal crossovers  during meiosis producing sperm or eggs, each  chromosome can include a mixture of   chromosomal segments from its two parents.   When genes are selected, the chromosomal  

segment (haplotype block) containing the gene is   along with many other “linked” genes in   the segment. Selection for positive traits will  cause the inheritance of a chromosomal segment from the parent(s) containing causative genes.  Selection against deleterious traits or diseases will   cause the loss of a chromosomal segment containing causative genes. As meiotic crossovers occur  producing sperm and eggs through the generations, the size of the chromosomal segment containing  genes under positive and negative selection can get smaller.  

As ancestors and dogs who pass on positive traits to the breed are linebred on (appearing in both the  sire and dam's sides of the pedigree) this can cause haplotype blocks to pair up - causing runs of  homozygosity (ROH). Even without close linebreeding, selection for positive traits will increase their  homozygosity having originated from distant ancestors. Breed-defining genes would be expected to be  collected in runs of homozygosity due to selection over time. 

Deleterious (primarily recessive) mutated genes can accumulate in the background of the breed gene  pool. These accumulate primarily because they are not expressed in the heterozygous (carrier) state.  Deleterious genes can increase in frequency if linked to positively selected genes, or through genetic  drift. An increasing frequency of breed-related disease will be due to homozygosity of deleterious  recessive or additive liability genes. Individual liability genes can cause embryonic death (thus resulting  in smaller litter size or infertility), increased neonatal death, or breed-specific genetic disease. This is due  to the expression of specific deleterious genes and not a general result of increased homozygosity. 

If disease liability genes are linked in haplotype blocks to positively selected genes, then dogs that demonstrate the positive traits and do not carry the disease-liability genes should be selected for  breeding. These dogs can occur due to phenocopies (selected traits due to other genetic causes), or due  to meiotic chromosomal crossovers that break the linkage between the positive and disease-liability  genes. If the positive and deleterious genes cannot be separated due to tight linkage (adjacent genes or  even multiple effects of the same gene) then this is not a healthy breed standard. The standard may  need to be changed, achieved through other selected genes or possibly through crossbreeding. 

As breeds develop and reproduce to a standard, their genetic difference from other breeds increases.  Runs of homozygosity for breed-defining traits and quality genes is a positive development, even though  it results in a loss of genetic diversity from genes that do not reproduce a standard or maintain health. The genetic diversity between breeds is large. This is why pure breeds can be separated by their DNA  signatures. Breed subgroups (conformation versus working or breed populations on different  continents) can also be differentiated based on their DNA. This can provide an important source of  breed genetic variation if needed. The genetic diversity within the breed should be small, so that the  breed reproduces itself to a healthy standard. This is the “big picture” of genetic diversity in dog breeds. 

The fine detail of genetic diversity within a breed concerns maintaining a healthy phenotype and  reproductive ability. Dogs from the breadth of the gene pool should be used for breeding as long as they  represent health and quality. Restricted genetic diversity is not an issue in pure breeds, unless there is no alternative direction to go for health and quality. 

DIFFERENCES BETWEEN BREEDS AND SPECIES 

The force of species evolution is natural selection - the ability to thrive and reproduce within the  species’ environment. Artificial selection that could be detrimental to species survival is not an issue in  the wild. Genetic isolation can create subspecies (often with multiple isolation events) and can cause  random genetic changes due to genetic drift. 

Endangered species can share several population parameters with breeds. Their population size is  usually small, and they have a closed population. In many instances, there is a limited foundation base  (founder genome equivalent). Endangered species can experience decreased fertility and ability to  thrive due to both genetic and environmental variation.

Genetic disease in endangered species occurs primarily through genetic drift. This is the random  accumulation of disease liability genes in the absence of selection. As carriers of recessive and additive  disease liability genes are healthy, they are not selected against and their genes are propagated in the  offspring. Who reproduces in the population is random, and if carriers reproduce, the liability genes are  passed on. When recessive disease liability genes pair up, or when additive genes combine to cross a  threshold, clinical disease results. 

Species survival plans (SSPs) were developed by population geneticists working with rare and  endangered species who have a limited number of available breedable individuals. With the assumption  that avoidance of homozygosity of deleterious recessive genes provides for the healthiest and robust  offspring, SSPs are designed to mate the most unrelated individuals together (through pedigree or  molecular genetic markers). This hopefully limits the expression of recessive disease-causing genes. SSPs  also work to maintain the breadth of genetic diversity (evaluating the rareness or commonness of  genetic background) in the species population. The only individual selection in SSP systems is to not  breed unhealthy animals. However, if an unhealthy animal represents a unique genetic background it  could still be used in matings to maintain genetic diversity. The goal of an SSP is successful reproduction  with the production of healthy, live offspring representing the diverse background of the species. 

Purebred breeding requires constant (artificial) selection for positive traits including health, and against  negative traits and disorders. Without constant selection for specific breeding goals and their associated  genes, the health and quality of the offspring will decline. The ability of selective pressure to create  change in the population is limited by the amount of variation that is present for the selected trait in the  breed. Selecting for heterozygosity as a goal and mating the least related parents together, erases the  differences between dogs in the breed that are required for selection. This limits the ability to apply  selective pressure for improvement. As a breeder selects for more goals in any mating, the amount of  selective pressure for each individual goal diminishes. I.e., it is easier and more productive to select for  one to three goals at one time than for eight or nine goals. Any selective pressure (selection goal) that is not specifically directed toward health and quality will diminish the selective pressure for both. 

SSP breeding systems are not appropriate for pure breeds. Only outbreeding for the most heterozygous dogs randomizes the positive and deleterious genes in the gene pool. Breed-specific genetic disorders are caused by liability genes that are already dispersed in the breed’s gene pool. Outbreeding will not decrease the frequency of these genes in the population. The clinical occurrence and frequency of such  disorders will not diminish based on outbreeding versus linebreeding. The disorder will just appear randomly in offspring from different matings. Outbreeding and linebreeding are tools, not goals. There are specific reasons for using either in planned matings.

IMPROVING BREED POPULATION HEALTH THROUGH HEALTH CONSCIOUS BREEDING Purebred dog breeds were developed through artificial selection when dedicated breeders judiciously purged dogs and their genes from the breed gene pools if they were unhealthy or did not perform to a  standard. Somewhere along the way, the responsibility to select for health and produce healthy  offspring disappeared from dog breeding. Today, people just breed dogs and expect healthy offspring. 

People decide which dogs get bred, and which get bred to each other. This is the difference between  natural selection and artificial selection. If artificial selection does not select for health, then there can be no expectation of genetic health. If artificial selection selects for breed characteristics that impair health, then breed-related disease is the natural outcome. Dog breeding is all about selection. In the planning of any proposed mating, the selection of healthy parents is paramount to the health of  the offspring. A pre-breeding health examination includes phenotypic examination of the major organ  systems for; musculoskeletal, cardiac, ophthalmologic, gastrointestinal, pulmonary, dermatologic and behavioral abnormalities. Medical history should be examined for episodic inherited disease that cannot  be identified on examination; i.e., allergies, seizures, bloat, bladder stones, cruciate ligament disease, etc. Dogs demonstrating hereditary disease should be selected against for breeding.

Pure breeds can also have breed-specific genetic disease due to more recent mutations. For many of these there are breed-validated genetic tests that can identify causative or disease liability genes, or genetic screening to identify affected dogs. The OFA Canine Health Information Center (www.ofa.org) and the AKC Bred With H.E.A.R.T. program (http://www.akc.org/breeder-programs/akc-bred-with heart-program/) both have breed-specific genetic testing requirements that have been determined by the parent breed club. All prospective breeding dogs should undergo a veterinary pre-breeding health assessment that covers screening and medical history evaluation for all common and breed-related genetic disorders. If all breeders include pre-breeding genetic screening in mate selection, then America’s dogs will be healthier.  

The advent of multiplex genetic panel testing (Mars Wisdom Health, Embark, etc.) provides genetic test  results for over 180 canine traits and disorders. Unfortunately, most of the disease liability genes tested  for in these panels are breed specific. Unless the gene(s) have been validated to cause clinical disease  in other breeds or mixed breeds, the test result may not have any significance in your dog. In addition, the panel tests utilize SNPs (single nucleotide changes) instead of testing for a mutation, so false positive  and negative results can occur.Breeding decisions regarding breed-validated liability genes should be  based on direct mutation and not SNP testing. 

Typical genetic counseling recommendations utilize the breeding of quality carriers to non-carrier dogs  and replacing the carrier parent with a quality non-carrier offspring. In this way breeding lines (and  breed genetic diversity) are not abandoned and testable disease liability genes can be lost in one  generation. If a valid genetic test is not available then selection should be based on genetic screening  and open health databases that identify relative risk of carrying disease liability genes. 

Health conscious breeders are fulfilling their ethical responsibilities to produce healthier dogs. If a breeder is not willing or able to provide official health screening results for the parents of litters, then  BUYER BEWARE! There will be no expectation of genetic health in the puppies. Without evidence of pre-breeding genetic screening, health guarantees that provide for a replacement of a family member once  the emotional bonds have been made are worthless. It is only a piece of paper written to excuse a  breeder from performing their ethical responsibility of pre-breeding health screening. 

There are many conversations concerning issues with dog breeding in America. Many people prefer the  predictable characteristics of purebred dogs. The “Adopt, Don’t Shop” movement promotes rescuing a  dog from a shelter instead of buying from a breeder. The fact is that there isn’t even a fraction of rescue dogs available to provide canine companionship to America’s families. This has created the “bred for  rescue” industry. Dogs will continue to be bred so that they can be our faithful companions. If any  purebred or mixed-breed mating is being planned, health-conscious breeding through pre-breeding  health examination, genetic screening and genetic testing should be performed. If the public demands  health-conscious breeding then the issue of genetic disease in dogs will change. 

“All dogs deserve to live healthy lives.” William J. Feeney, Chairman of the AKC Board of Directors.