dog foot print and dna diagram

Essays on Dog Genetic Diversity

Inspired by conversations hosted by Jemima Harrison

The purpose of this website is to host essays and information about maintaining viable populations of healthy pure bred dogs

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copyright © 2009 by Dr Susan Thorpe-Vargus

Chapter 3


The age-old problem for dog breeders of course is that the characteristics they are trying to breed for do not always materialize in a litter of puppies. Or some unwanted characteristic keeps appearing that even “careful” breeding cannot eliminate. Why does this happen and what can be done to eliminate at least some of the uncertainty a breeder faces?


Keep in mind that the number of genes in the entire dog genome has been estimated to range from 30,000 to 100,000. Thus the breeder is dealing with a very large number of variables. Remember that every gene is the blueprint for either regulatory RNA, a protein or a snippet of amino acid called a polypeptide, but these gene products are not being made all the time nor at the same time. Regulation of expression involves turning genes on and off at various intervals and in a particular temporal sequence.

The first step in gene expression begins with transcription. This is the process of copying a DNA sequence called the template, into a single strand of RNA known as the primary transcript. This operation is initiated by an enzyme called RNA polymerase. Genes come in two types, structural and regulatory. RNA polymerase is a protein that is coded for by a regulatory gene. Transcription starts when this enzyme binds to a special region at the start of the gene called the promoter and continues until it reaches a terminator sequence. The first point of control in this process is therefore the binding of the enzyme to this specific site.

While all genes are present within a cell, only certain genes within any cell express themselves through a process called cell differentiation. Have you ever asked yourself why are the cells in your fingernails only producing fingernail proteins and not, lets say, eye proteins? The simple answer is that all the other genes in the cell, except those coding for fingernail proteins are somehow turned off.

In the process of maturation, a cell progressively and irreversibly becomes more committed to a certain line of development. One of the ways scientists think a cell can ‘remember’ what it has decided to be seems to depend on the chromosomes. Control of gene expression is the result of regulating transcription initiation. Chromosomes play a unique role in this process. It is possible to see cellular DNA only during certain phases. Most of the time it exists in a relatively uncondensed form and it is only during this dispersed phase that transcription can occur. However, even during this stage, some parts of the chromosomes stay tightly wound up and condensed. The part that is unwound is called euchromatin and it is transcriptionally active. The part that stays condensed cannot be transcribed because the transcriptional factors are physically unable to get to the DNA.

There are two types of inactive chromosomes. One is called constitutive heterochromatin and it is always transcriptionally inert. The other is referred to as facultive heterochromatin and it varies in a tissue-specific manner. So, depending on which cell type it is, large blocks of chromosomes are physically prevented from being transcribed. This constitutes regulation at rather a gross level, a finer aspect of control exists in the specific sequence of the DNA itself.

Another form of gene regulation can result in an entirely new protein being made or, in some cases, no gene product at all. This can happen through the selection of alternative transcription initiation sites or optional splice sites. An additional control mechanism has been suggested by the processing of messenger RNA. It is mRNA that is actually translated into the final gene product. Whether or not messenger RNA makes it out of the nucleus so that it can be made into a protein, or how long it lasts before it is degraded, would definitely affect the final gene product. However, research has barely begun on these topics, so we will leave it for now to discuss another pathway to phenotypic differences.


– DOMINANT AND RECESSIVE GENES Control of gene expression also depends on how genes interact and their alternative alleles. Because chromosomes are present in pairs, it stands to reason that the genes on them are also present in pairs. Genes in corresponding locations on homologous chromosomes are called homologous genes, and when these homologous genes can code for different proteins, they are called alleles. Sometimes we are aware of only two possible alleles for a particular gene, but often several possible alleles exist. Only two at a time can be present in one individual, however.

The possibility of having either identical or nonidentical allele members of a pair creates an array of different ways these alleles can interact. When one allele can completely mask the presence of the other it is termed complete or simple dominance. If both alleles can be expressed equally then codominance occurs. Sometimes the end result may be intermediate between the products of the two alleles generating incomplete dominance.

The gene can be considered a small business with two partners. Sometimes both partners share the same desires, just as both alleles may code for the same products. This is the situation with homozygous alleles. Sometimes partners, and alleles, don’t agree, such as with heterozygous alleles. Heterozygosity can have several outcomes. As in any “partnership”, decision making can take several forms. In some cases one partner (the dominant allele) calls all the shots, regardless of the wishes of the other (recessive allele). In genetics this is known as simple dominance. In other partnerships, compromise is the order of the day, and when the two partners are not in agreement, they settle on an intermediate solution (incomplete dominance). In yet other partnerships, both members go ahead and do what they want to do regardless of what the other does. In genetics such a solution is termed co-dominance.

Simple dominance

Dog breeders sometimes fall into the trap of assuming a trait is due to a dominant allele because “even after being hidden for generations it just popped back out…I can’t seem to get rid of it”. In fact, they have put their finger on the signature of the recessive allele. Consider the case of black versus liver hair color. A single dominant allele (B) codes for black pigmentation. Dogs that are either BB or Bb will be black and indistinguishable from one another. The “science speak” way of describing this is to say that the genotype is different but the phenotype is the same. In the case of two recessive alleles, bb, liver color result. If two liver (bb) dogs were bred together, they could only produce liver offspring. If two black dogs were bred, the possibility exists that both of those dogs could be heterozygous (Bb) and produce a bb offspring that would be liver--not because the liver was dominant, but because it was recessive and thus hidden in the parents. A trait caused by a dominant allele can be traced directly from one ancestor to the next through a pedigree, although, as we will see later, other genes can also act on the dog’s color to possibly modify or obscure it. Not all traits are inherited in this manner, however. In fact, most traits do not show simple dominance.

Incomplete dominance

In contrast to simple dominance, in which two alleles produce three possible genotypes but only two possible phenotypes, incompletely dominant allele pairs produce three possible genotypes and phenotypes. The merle coat color pattern (found in breeds such as the Australian Shepherd, Dachshund, and Collie) is an example of an intermediate phenotype created by two non-identical (M and m) alleles. Dogs that are mm have “normal” non-merle coat colors determined by genes at other locations. Dogs that are Mm display the classic merle color, in which areas of the coat have loss of normal pigmentation, resulting in the appearance of flecks or patches of normally colored hair interspersed among lighter hair. Dogs that are MM have greater pigment loss, may be nearly white, and very often have visual and auditory problems that are pigment related. Breeders thus usually discourage merle to merle breeding, since ¼ of the progeny of a Mm x Mm breeding would be MM—and therefore likely to have vision and hearing problems. Instead, taking advantage of incomplete dominance, merles (Mm) are best obtained by breeding non-merles (mm) to merles (Mm), resulting in litters consisting on average of 50% Mm merles and 50% mm non-merles. Two simple tests can determine if a trait is incompletely dominant. For one, crosses between two different parental types should always result in the intermediate type. For another, crosses between two intermediate types should result in both intermediate as well as parental types.


In yet another example, other alleles code for products that can both be distinguished in the individual. The most common examples of this codominance are usually found in certain blood proteins expressed in both people and dogs. Perhaps the simplest and most familiar are human blood groups. In humans, three possible alleles exist: A, B and O. A and B are dominant over O, but are codominant with each other, thus resulting in the AB blood type.

Penetrance and Expressivity

Just when early researchers thought they had dominant and recessive inheritance clearly defined, they kept coming across cases where an allele that should have been expressed wasn’t. The most obvious were in identical twins that weren’t quite identical. One would exhibit a trait known to run in that family while the other would not, yet they were identical in all other respects. This is known as variable penetrance. Related to this is the concept of variable expressivity, where both twins would share the same trait, but one would have a more pronounced version of it than the other. Two dogs that both carry the same alleles for spotting may have very different spotting patterns. For some reason some alleles will not always be expressed, or will be expressed to varying extents, in an individual that should normally express them. For the breeder, these two phenomena can make tracking the hereditary pattern of a trait more complicated.


Some genes affect widely disparate traits. Chinese Cresteds come in a hairless and powderpuff varieties, with the hairless caused by a single allele H. In fact, this is a homozygous lethal allele, because dogs with HH die before birth so hairless dogs are all Hh. The H allele not only results in hairlessness, but also in tooth abnormalities, which is why allowances are made for hairless Cresteds with missing teeth. Because these two traits are pleiotropic i.e., the effects of one allele, they cannot be separated and one must always go with the other.

In addition to the interactions that occur between alleles at the same locus, interactions can also occur between alleles at different loci. Examples of traits involving different loci include the concepts of phenocopies, linkage, epistasis, and perhaps most important, polygenic effects.


Sometimes two dogs will seem to share the same trait but in fact the trait is the result of totally different genes. White dogs can result from the alleles for extreme white spotting (basically a spotted dog without any spots showing) or from a dog with several alleles at different loci for factors that make the coat pale (basically a cream dog that is so pale it appears white). The eye disease, Progressive Retinal Atrophy (PRA) exists in many breeds, sometimes appearing clinically identical, even though the genetic cause is different. This means that even though PRA is recessively inherited in affected dogs, crossbreeding different breeds may yield normal offspring because unique genes in the two breeds cause the disease. (If an affected dog of breed A is pp RR, and an affected dog of breed B is PP rr, then their offspring would all be Pp Rr, and appear normal). For example, Irish Setters and Collies have genetically distinct forms of PRA.


Not only can alleles interact with other alleles at the same locus, but in some cases, with alleles at other loci. While dominance can be considered an intralocus interaction, epistasis can be considered an interlocus interaction. The simplest case of epistasis occurs when the presence of one trait effectively masks the presence of another trait. Such an example occurs with Labrador Retriever coat colors. At the B locus, the dominant B allele codes for black fur (BB or Bb) and the recessive b allele for chocolate fur (bb). However, at a totally different locus, E, the presence of the dominant E allows either black or brown fur (according to what is determined at the B locus), but ee restricts the formation of any dark pigment, thus resulting in a yellow dog no matter what is coded for at the B locus.

Another form of inheritance (above the genes) includes a phenomenon called epigenetics. Imprinting is an example of this. Normal development requires genes to be inherited from both parents. Genetic imprinting is the situation where the expression of the gene is determined by which parent you inherited the gene from. Some disease genes are expressed as an entirely different disease, depending upon whether you inherited the gene from your mother or father. Imprinted genes occur in those regions of specific chromosomes with allelic differences in transcription and methylation. A mutation within an imprinting region can cause genetic abnormalities. In humans, Prader-Willi syndrome (PWS) and Angelman Syndrome (AS) are examples of two different disorders, with entirely different phenotypes, that are caused by either a maternal or paternal deletion on chromosome 15 or when the inheritance of both chromosomes is from just one parent (uniparental disomy). Only paternal deletions are seen in PWS and only maternal deletions are seen in AS. When both copies of chromosome 15 are inherited solely from the mother the disease presents as PWS and just the opposite when AS is seen.


The problem dog breeders have with using ideas of dominant and recessive genes in breeding dogs is that most traits don’t appear in discreet intervals, but instead are continuously distributed over a range of values. This is also called a quantitative trait. For instance, dogs don’t come in just short, medium, and tall, they come in all sizes. Even within a breed, height is normally distributed in a bell curve. This is because many important traits are the result of many pairs of genes acting together. In these cases, the extent of a trait is determined by gene dosage, which is the number of particular alleles present in a genotype.

Imagine that height is controlled by incompletely dominant alleles at three different loci, A, B, and C, with A+, B+, and C+ all coding for an additional half inch of height. A dog with the genotype A+A+, B+B+, C+C+ would be three inches taller than one with the genotype AA, BB, CC. In fact, 27 different genotypic combinations are possible in this example, resulting in seven different heights. The more loci involved, the greater the number of possible genotypes and phenotypes, until the phenotypes become so numerous that they appear to be continuously distributed. This blending is further influenced by environmental factors. In fact, all quantitative traits have an environmental component. A good example of this in the canine would be hip dysplasia. Hip dysplasia is a disease that is known to be influenced by the amount and quality of food that the puppy eats.6


The fact that gene expression can be influenced by the environment should not be surprising. The value of how much the expression of a trait is genetically determined is called heritability. This value ranges from 0 to 1 and the higher the value the more likely that selection will play a role in the inheritance of that trait. What should also be stressed is that the heritability of a trait in one group cannot be compared to that of another group. Heritability is strictly a function of a particular population, at a specific time and place. One should also be aware that no matter how high the genetic heritability of a trait there will always be some environmental component in the expression of that trait.

Linkage and Linkage Disequalibrium

In a highly inbred population, genetic defects can become fixed rather rapidly if they happen to be on the same chromosome as a gene that codes for a desirable trait. The closer they are physically on the chromosome the tighter they are ‘linked’. These genes and their respective alleles will be inherited together unless they become ‘unlinked’ in a procedure called crossing over or recombination. This is a process that occurs during the formation of gametes. At that time, homologous chromosome pairs exchange segments of their DNA structure. Such closely linked genes are said to be in a state of linkage disequilibrium. When a breeder selects for or against a specific gene trait, he or she may also inadvertently be choosing other traits which are located on the same chromosome. One should remember this when making a breeding decision. Severe selection pressure against an unwanted trait could result in throwing the baby out with the bathwater and the permanent loss of a necessary or desirable attribute.

Sex Linkage

A special case of linkage exists when genes are located on the sex chromosomes. Unlike the other 38 pairs of chromosomes, the sex chromosomes are not always paired in a homologous fashion. This is simply because sex is determined by whether an individual has two X-chromosomes (XX=female) or an X and a Y chromosome (XY=male). The Y chromosome is a very small chromosome and until recently there were doubts that any significant information was contained on it. Those genes found on the Y chromosome that have been identified, code specifically for male traits. The X chromosome is larger and is known to carry on it genes that code for several traits important for males as well as females. Genes on the X chromosome are not matched by genes on the Y chromosome, negating the possibility of allelic pairs.

In the male, whatever alleles are on his single X-chromosome will be expressed (a condition known as hemizygous). In the female, the situation is different than what is seen in the autosomal (nonsex) chromosomes. For many years it was assumed that X-linked alleles acted just the same as autosomal alleles. They don’t. Instead of acting in a standard dominant/recessive way, these alleles act more like codominants. In placental mammals one of the two X-chromosomes is randomly inactivated in each cell of the body. The remnants of these inactivated chromosomes can be seen as dark spots, called Barr bodies, in almost every cell of a normal (XX) female, but not in normal (XY) males because they must have a functioning X chromosome. However, researchers at the National Institute for Medical Research, UK, have recently discovered that the "silent" X chromosome in females is not entirely silent - some of the genes evade inactivation, meaning females actually express more genes than their male counterparts. Approximately, 15% of genes escape inactivation altogether, each of which now becomes a candidate for explaining some differences between males and females. In addition, another 10% are sometimes inactivated and sometimes not, giving a mechanism to make women much more genetically variable than men. Very early in embryonic development both X-chromosomes are apparently active, but then most of the duplicate chromosomes are rendered dysfunctional by staying tightly condensed in the heterochromitin state. It is entirely a matter of chance whether it is the paternal or maternally derived X chromosome that is inactivated in any given cell, but once inactivated; all subsequent cells derived from that cell will continue to have the same inactivated X chromosome. In individuals with visible sex-linked traits the results can be clearly seen as patches of paternally and maternally derived traits. Thus, all female mammals are mosaics.

The best known example is the calico cat, which is almost always a female (the few males are abnormal XXY individuals) displaying a patchwork of black and orange colors, each patch representing a clone of an original cell that randomly inactivated either the X chromosome with an allele for orange fur or a the X chromosome with the allele for black fur. In dogs, we have to look a little more carefully for such evidence. Examples include X-linked muscular dystrophy in Golden Retrievers and X-linked hereditary nephritis. Because these female carriers are mosaics for the abnormalities seen in these diseases, they may exhibit attenuated signs of the disorder, with the severity depending upon the proportion of the mosaic derived from the X chromosome that carried the abnormal allele. Sex-linked traits will be passed from dams to sons via one of her X chromosomes. Because sires have only one X chromosome to pass on to their daughters, in order for the trait to be fully expressed in a female, she must have an affected sire and carrier (or affected) dam. The degree of mosaicism that the dam expresses is random and does not affect the chances of her offspring being affected or the severity of that trait in those that are.

Misunderstandings about sex-linked inheritance have given rise to many breeding myths, the most widespread of which place greater emphasis on the “sire line” (sire to grandsire) in the belief that “what you see is what you get” is due to the single X chromosome, as well as the belief that important breed attributes are carried on the Y chromosome. Some also contend that whether an ancestor is on the dam versus the sire’s side of the pedigree is of prime importance. These theories neglect the fact that the Y chromosome contains few, if any, identified genes apart from those involved with male reproduction, and that that the sex chromosomes are but one of 39 pairs of chromosomes. These ideas served the 19th century breeder well enough, having been developed well before the birth of genetic science, but they have no place in the 21st century breeder’s arsenal.

So, the variety of appearance between dogs of different breeds is controlled at several different levels. Some types of expression seem to depend upon turning control/regulatory genes on and off so that a specific developmental cascade is expressed. Other phenotypic differences must rely upon the interaction of genes, their various alleles and where these hereditary units are located on the chromosomes. Hopefully, the modern breeder will be able to use this knowledge to make more informed choices when planning a breeding or to understand why certain breeding decisions went awry.

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