Understanding canine genetics

The sum of a dog’s genetic material can be thought of as a cook book which is split into chapters containing recipes. These recipes are the dog's genes and the letters that make up each recipe is its DNA. Just as a recipe can be used to make a dish of food, a gene can be used to make a protein, a building block of a dog's body.

Read the following information to find out what DNA is, how a gene is made and how these translate into a dog’s body. Learn what happens when genes, or translation, goes wrong and how this can impact on a dog's health.

DNA, genes and chromosomes

What is DNA?
DNA, or deoxyribonucleic acid, is found in all known living things and acts like a set of biological instructions. These instructions make every breed, species and dog (apart from identical siblings) unique. DNA is found in nearly every single cell in the body, apart from red blood cells, and tells a dog's body how to grow, develop, work and reproduce.
How are a dog’s genetic instructions stored?
A dog’s genetic instructions are stored as a type of code that is made up of units called bases. There are four different bases found in DNA and these are named adenine (A), guanine (G), cytosine (C) and thymine (T). Each base unit is linked to a sugar molecule and a phosphate molecule, which allows a string of bases to form. Just as a sequence of letters can be used to form words, and words be used to form sentences, so too can the sequences of bases on the string be used to produce the proteins that make up each organism. Proteins are the building blocks for every organism and make up bones, teeth, hair, muscle etc.
The importance of DNA's structure
Two complementary strings of bases lie parallel to one another and lock together to form a structure similar to a spiral staircase, called a double helix. Bases from each of the two strings zip together to form the “steps” of the structure. Each base will only bond to a specific partner base, e.g. adenine always bonds with thymine, and cytosine always bonds with guanine. This feature of DNA is particularly important when it comes to producing new cells with the same DNA, which is vital for growth, maintenance and repair. When cells divide, the double helix structure unzips, freeing up each of the two strings of bases to bond to another set of bases, therefore producing two copies of the original DNA.
How many base pairs does a dogs DNA have?
The dog genome (the sum of its genetic material) contains 2.8 billion base pairs of DNA.
What is a gene?
A gene is a section of DNA that has specific instructions for making a particular molecule, usually a protein. Each dog has two copies of every gene, one of which is inherited from its mother and one from its father. These two genes may be the same or they may be slightly different. These different versions of the same gene are called alleles. These differing genes contribute to each dog’s unique physical features and account for the differences between each dog and each breed.
How many genes does a dog have?
There are around 19,000 protein coding genes in the dog genome.
What is a chromosome?
Chromosomes are structures found inside a cell’s nucleus (the core of a cell) and are composed of DNA wound around proteins. The structure of a chromosomes keeps DNA tightly packed and wound around spool-like proteins called histones. Without these structures, DNA would be far too long to fit inside each cell. If unwound and placed end to end, the DNA from one dog’s cell would reach up to several feet long. In order for a dog to function, each cell must frequently divide and replace old cells with new ones. Chromosomes ensure that DNA is evenly distributed and are accurately copied during cell division.
How many chromosomes does a dog have?
Each cell in a dog’s body contains 39 pairs of chromosomes.

Traits and inheritance

Dog breeders carefully choose which dogs to breed from based on a number of different characteristics, such as the way it looks, its general health, its temperament, etc.

A breeder’s aim will be to produce puppies that have similar desirable characteristics to their parents. The process of passing characteristics from parent to offspring is known as inheritance, but how are these traits determined?

What controls characteristics?
How a dog looks and behaves is determined by a combination of the environment it lives in, the environment it has grown up in and its genetics. Environmental factors could include a dog’s diet, how much exercise it gets or the levels of hormones in the uterus it was raised in when it was an embryo. A dog’s genetics are determined before its birth and are the only way in which characteristics can be passed from parent to child, e.g. a dog’s coat can be influenced by what it eats, sunlight, time of year, how short it is trimmed etc., but none of these factors will impact the coat of the puppies it has in the future, while its genes on the other hand will.
What is the function of a gene?
A dog's genome (the sum of its genetic material) can be thought of as a cook book which is split into chapters containing recipes. These recipes are the dog's genes and the letters that makes up each recipe is the DNA. Just like a recipe can be used to make a dish of food, a gene can be used to make a protein. Proteins are the building blocks for ever organism and make up bones, teeth, hair, muscle, etc. Genes are therefore vital in producing proteins which impact on a dog's characteristics.
Alleles give variation in characteristics
Each dog has two copies of every gene, one of which it inherited from its mother and one from its father. These two genes may be the same or they may be slightly different. Different versions of the same gene are called alleles and can cause variation in the protein that is produced, or where, when and how much of the protein is produced. These differences in how the protein is produced contribute to each dog’s unique physical features and account for the differences between each dog and each breed.
Homozygous and heterozygous
When a dog has two copies of the same allele they are said to be homozygous. When the two alleles they have are different, they are known as heterozygous.

How are genes passed from parent to offspring?

A dog’s sex cells (sperm or an egg) contain only half of its DNA, with one of each allele being randomly selected. When a sperm and egg come together to form a new set of DNA, the two halves combine, so that each puppy has two copies of every gene, one inherited from its mother and one from its father. 

Genotype and phenotype

The combination of alleles a dog has is known as the genotype. The physical characteristics a dog has in known as its phenotype. How the genotype (the dog’s genes) influences the phenotype (the way it looks) is not always straightforward, but some of the mechanisms of gene expression are outlined below.

Dominant and recessive alleles

Alleles can be said to be either recessive or dominant. A recessive allele is only expressed (influences the characteristics of the dog) if both alleles are the same. A dominant allele on the other hand is always expressed, even if it is accompanied by a different allele.

A genetic diagram (or punnett square) can be used to show how dominant and recessive alleles work. Letters are used to symbolise the genotype (the alleles a dog has). A capital letter represents a dominant allele and a small letter represents a recessive allele. The example below shows a made up punnett square for coat colour with the B representing a dominant allele for brown fur and the b representing a recessive allele for blonde (or yellow) fur.  In the example below, both parents have a genotype of Bb. Since the B is dominant, then any offspring that has a Bb or BB will be brown, while offspring that has two copies of the recessive b will be yellow.

  B b
B

BB

(Brown fur)

Bb

(Brown fur)

b

Bb

(Brown fur)

bb

(Yellow fur)

Intermediate expression

A blending of phenotypes can sometimes occur when an individual has two different alleles. Using the example in the punnett square, an individual with BB would still have brown fur, an individual with bb would still have yellow fur, but an individual with a B and a b would have a coat colour somewhere between the two. 

  B b
B

BB

(Brown fur)

Bb

(light brown fur)

b

Bb

(light brown fur)

 

bb

(Yellow fur)

Codominance

For some characteristics, two alleles can both be expressed at the same time. A good example of this is the blood type AB in humans. Individuals with type AB blood produce both type A and type B blood.

Multiple allele series

These are traits that have more than two possible alleles. A dog will still only have two copies of each gene, one from each parent, but there will be a variety of possible alleles within the population. A good example of this is once again blood type in humans, where there are three possible alleles, iA, iB or i.  An individual can therefore be iAiB, iAi, iBi or ii. Having more than two alleles increases the possibilities of the phenotypic characteristics in a population.

Modifying genes

These genes influence the degree to which other genes control their characteristics, e.g. the coat colour pattern of piebald spotting (pigmented spots on an unpigmented white background) in dogs can be more colour and less white, or more white and less colour, depending on whether a plus modifier or minus modifier is present.

Epistatic alleles

Sometimes the effect of one gene can mask the expression of another unrelated gene. Coat colour in Labrador Retrievers is a good example of this. A black coat colour allele (B) in Labradors is dominant, while a brown coat (chocolate) allele (b) is recessive. Despite this, a second gene found in a different area of DNA can override these and create a yellow coat. A yellow coat is produced a Labrador is homozygous recessive, i.e. has two copies of a recessive allele.

Coat colour Genotype
Black BBEE, BbEe, BbEE, BBEe
Brown (chocolate) bbEE, bbEe
Yellow BBee, Bbee, bbee
Regulator genes

These genes can either switch on, or switch off the expression of other genes. These regulator genes are commonly used during development, soon after conception, and are used to ensure that certain proteins (and therefore parts of the body) are made at the correct times. These genes are also used as a dog develops and changes throughout its lifetime.

Incomplete penetrance

Some genes do not have an impact on the individual unless certain environmental factors occur, e.g. the genes that cause multiple sclerosis in humans can be triggered by the Epstein-Barr virus.

Sex-limited genes

These are genes inherited by both men and women, but are usually expressed by only one of the sexes. A good example of this would be the genes that control the amount of milk a female dog can produce, which will be found in males, but will not be expressed.

Sex-controlled character

These are genes that are expressed in both sexes, but in a slightly different way. An example of sex-controlled genes is gout in humans. Both men and women can have the genes, but 80% of men who have the gene develop gout, while only 12% of women are affected.

Genome imprinting

Some genes can have a different impact depending on the sex of the parent that they were inherited from. If an allele from the father is imprinted, then is silenced, or doesn’t work, and only the allele from the mother is expressed and visa versa.

Pleiotropy

One gene can sometimes be responsible for two or more characteristics, e.g. the gene for a merle coat colour can increase the risks of deafness and eye defects when a dog has two copies of the merle allele.

Stuttering alleles

Some inherited diseases become more severe with each generation that inherits them. Segments of these defective genes are doubled with each generation and so worsen the effect.

Complex inheritance

Many characteristics are controlled by more than one set of genes and are known as polygenic traits. A good example of this will be your dog’s size, which will be controlled by the large number of genes which produce their legs, paws, back, head, etc.

Coat colour and eye colour can also be controlled by a number of different genes and may not be inherited in a simple way.

From DNA to protein

What is a protein?
Proteins are the building blocks for ever organism and make up bones, teeth, hair, muscle, enzymes, antibodies etc. Proteins are used in the body for structure, function and regulation. These large, complex molecules are made up of long chains of smaller units called amino acids. There are around 20 different types of amino acids that can be used to make a protein, with the order of amino acids determining the protein's structure and function.
How are proteins made?
DNA, or deoxyribonucleic acid, is found in all known living things and act like a set of biological instructions. These instructions are stored as a type of code that is made up of units called bases. There are four different bases found in DNA and these are named adenine (A), guanine (G), cytosine(C) and thymine(T). Each base unit is linked to a sugar molecule and a phosphate molecule, which allows a string of bases to form. Just as a sequence of letters can be used to form words, and words be used to form sentences, so too can the sequences of bases on the string be used to produce the proteins that make up each organism. The sequence of bases that produces a protein is known as a gene. In order for a gene to be expressed, or a protein be made, a two-step process is required.
Why are two steps required to make a protein?
DNA is stored in every single cell (apart from red blood cells) and is kept in the nucleus, the core of each cell, to prevent it from being damaged. Proteins are made in a thick solution, called the cytoplasm, which is outside of, and surrounds, the nucleus. Two stages, known as transcription and translation, are needed in order to get the information held in the DNA out of the nucleus and converted into a protein in the cytoplasm.
What is transcription?

This is the first step in decoding DNA’s code. In the cell’s nucleus, a copy of the code is made in order to transport it out of the nucleus and in to the cytoplasm. To initiate this process, the DNA molecule unwinds and separates. An enzyme (RNA polymerases) travels along the unwound DNA and builds a new complementary version of the code, called RNA (ribonucleic acid). RNA is similar to DNA apart from

a) it is single stranded,
b) the sugar molecule has different chemical properties (RNA is made up of ribose instead of deoxyribose),
c) It uses the base uracil instead of thymine and
d) because RNA is single stranded, it does not form a helix

The particular type of RNA that is made is called messenger RNA (or mRNA) because it carries the information, or message, from the DNA in the nucleus into the cytoplasm.

What is translation?
This step occurs in the cytoplasm of the cell where the mRNA interacts with a ribosome. This is a structure that translates the base sequences of the mRNA into amino acids, the building blocks of a protein. Three bases in a row create a unit called a codon. One codon creates one amino acid. Another type of RNA, known as transfer RNA (tRNA), helps to construct the protein, one amino acid at a time until the ribosome comes across a specific codon which tells it to stop.
How is protein production regulated?
Each cell turns expresses only a small number of its genes, while the others remain switched off. The way in which these genes are turned on and off is called gene regulation. Gene regulation ensures that each cell looks and acts appropriately according to its function, e.g. the proteins produced by liver cells and muscle cells will be specific to their role. Gene regulation usually occurs during transcription, although it can occur at any point of gene expression.

Mutations and disease

Why do inherited conditions occur?
Each dog has two versions of every gene, one that it inherits from its mother and one that it inherits from its father.  Copies of these variant genes are made by each parent when they produce sperm or eggs and these are passed on to their children. When these genes are copied to produce the sperm and eggs, errors can occur, creating mutant genes (or incorrect copies of recipes if we maintain our analogy). 
The impact of a mutation
Dogs that inherit a faulty gene will make a copy of the error and can pass it on in turn to their descendants. Just like an incorrectly copied recipe, the impact it can have will depend on the type of error made. A spelling mistake of a common ingredient in a recipe may have no impact whatsoever, while the changing of a cooking time could have severe consequences. Similarly a mutant gene may have no apparent effect, or it could cause a serious health problem.
What type of error can occur?
The most common type of error to occur is when a single base is substituted for another. Sometimes a base may be deleted, or an extra base may be added or changed. Regardless of the error, most cells usually repair any accidental changes, but errors that are not corrected in cells that become an egg or sperm will be passed on to any offspring.

The DNA sequence of a gene can be changed in several different ways:
  • Missense mutation: one base pair is changed and the type of amino acid that is produced is different
  • Nonsense mutation: one base pair is changed which causes the cell to stop building a protein where the error has occurred. This results in a shortened protein that may not function correctly, if at all
  • Insertion: when one or more bases are added into a region of DNA
  • Deletion: one or more bases may be removed from a sequence of DNA
  • Frameshift: each strand of DNA is made of sequences of bases which are “read” in groups of threes, called codons. Each codon produces one amino acid. The deletion or addition of one or more DNA bases can change the way in which a gene is “read”, shifting the reading frame along and resulting in a faulty protein
  • Point: just one base is changed in a DNA sequence – this may be silent, missense or nonsense
  • Silent: a change that occurs still produces the same amino acid as before and has no impact on the protein produced
  • Splice site: a change to a number of bases that causes a gene to be incorrectly copied into mRNA during transcription
  • Chromosomal translocation: part of a chromosome that reattaches in the wrong place
Is a mutation always bad?
Not all sections of DNA code for a gene. In fact, most changes to DNA usually occur in the vast areas of DNA between genes, and so have no effect. Changes to areas that code for genes can sometimes mean that proteins are not made correctly, are produced in the wrong quantitates or not made at all. When a mutation does occur in the areas which produce proteins, it is likely to simply cause a different version of the gene resulting in a different characteristic, which is neither good nor bad (i.e. different hair colour or ear length). It is unusual for these changes to be serious or result in death or disease, but it can occur.

When can mutant genes cause health problems?

Autosomal-dominant condition

A health condition that can occur when a dog has only one copy of a faulty gene (either inherited from its mother or its father). Many of the more severe autosomal-dominant conditions are generally not passed on to any further offspring because the dog is often too ill to reproduce, or dies before it reaches sexual maturity. For this reason autosomal-dominant conditions are usually quite rare.

Autosomal-recessive condition

A health condition that can only occur when a dog has two copies of a faulty gene (inherited from both its mother and father) is known as an autosomal-recessive condition.

Dogs with only one copy of the mutant gene are said to be carriers and are unlikely to show any sign of the disease, but can pass the gene on to their offspring. The mutant genes for autosomal-recessive conditions can be the most difficult to predict, because they can be passed on from generation to generation without being noticed or identified. 

As long as the dog also has a healthy copy of the gene to do its normal job, then the mutant gene may never be noticed. Often, there is no way to know that these mutant genes exist, or what they cause, until they are expressed in a dog with two copies.  Every organism, including dogs and humans, are carriers for many autosomal-recessive conditions which have been passed from generation to generation without ever being noticed.

Complex inherited disorders

Complex inherited disorders are often caused by a number of different genes and are also influenced by environmental factors, such as diet and exercise. The way in which these conditions are inherited is not straightforward; hence the name complex inherited disorders. 

One allele may increase or decrease the chance of a condition developing, but the impact actually be very slight. Lots of genes may contribute to the risk of a dog developing a condition and have an additive effect.

X-linked inheritance

Each individual has two sex chromosomes. Men have an X and a Y chromosome and women have two X chromosomes. Some conditions result from a mutation on the X chromosome. These conditions don’t usually significantly affect females because they usually have one normal copy of the X chromosome which can counteract the mutated chromosome. Although women may not be affected by X-linked conditions they can still be a carrier. If a male inherits a mutation on the X-chromosome, he will develop the condition because he only has one X-chromosome. 

Chromosomal conditions

Rather than a condition being caused by a mutation of a specific gene, chromosomal conditions occur when an individual has too many or too few chromosomes. These conditions are not usually inherited but can occur randomly before or soon after an egg is fertilised.

Gene pools and the impact of selection

What is a gene pool?

A gene pool is a hypothetical collection of all the variations of genes in a population. This could be a population of rabbits in a field, fish in a pond, or dogs in a breed. In a closed population, such as pedigree dogs, the numbers of gene variants is unlikely to increase, unless new dogs are brought into the breed, or mutations occur (which is rare and usually harmful). A gene pool can, and most likely will, get smaller when genes are lost through complete chance (i.e. not passed on to any descendants), or when dogs do not reproduce. 

Sometimes an animal having a certain trait can influence how likely it is to survive and/or reproduce, this could be a faster rabbit evading a fox, a better camouflaged fish not being seen by its predators, or a pet dog having a good temperament and being chosen for breeding. All of these selection pressures can, over time, shape a population, making some genes associated with these benefits more common, while others become rarer or are lost from the gene pool.

How does selection impact a gene pool?

Dog breeders will choose carefully and select dogs that possess specific desirable traits, such as an excellent level of health and good temperament. By applying a selection pressure, (or a breeding criteria), to a breed, it makes some traits, and the genes that control them, more common, while others which control less desirable traits become rarer.

Dogs with desirable traits are likely to be bred from more frequently, while others that do not possess these traits may not be used for breeding at all. Over time, the gene variants associated with these popular dogs become common in the breed, while those associated with the less desirable dogs may be lost and disappear forever. These lost genes may include those that controlled the less desirable traits, but may also include other genes that just happened to be found in the less desirable dogs.

e.g. if a longer coat is desirable, then dogs with a long coat are more likely to be bred from and pass on their genes. Dogs with a short coat may not be bred from at all and so will not pass on any of their genes. These lost genes may include those that produce a shorter coat, but also includes all of the other genes that contributed to the rest of the dog, i.e. its eye colour, leg length, quality of hips, temperament etc.

What impact can a shrinking gene pool have on a population?
If a population is made up of 100 dogs and there are 50 different variations of each gene, then the likelihood of finding two dogs with the same genes is small. If over time the number of dogs stays as 100, but the number of gene variants shrinks down to 10, then the likelihood of finding two dogs with same genes is much higher. These dogs will have inherited their similar genes from an ancestor that featured in both their pedigrees and so they are, to some degree, related. Therefore, as the gene pool shrinks, the likelihood of two related dogs mating increases. The mating of related dogs is known as inbreeding. As inbreeding increases, so too can the risk of health problems occurring within the population.

Understanding inbreeding and the importance of genetic diversity

What is inbreeding?
Inbreeding occurs when animals that are related breed. Many people automatically associate inbreeding with close (or incestuous) matings, such as a father to daughter mating (which are banned by The Kennel Club), but this could also include the mating of more distant relatives. Related dogs are likely to share similar genetic material, with closer relatives sharing more genetic material than distant relatives. 
The pros and cons of mating related dogs

Mating two relatives that share similar genetic material means that their children are expected to be more alike and therefore have more predictable traits, e.g. mating two Labradors together will produce offspring that are Labrador shaped, while mating a Labrador to a Poodle can produce a range of different offspring. Although producing puppies with more predictable shapes may be beneficial, close inbreeding can come at a cost.

High degrees of inbreeding can lead to inbreeding depression (reduced litter size, increased puppy mortality, reduced fertility, a shorter lifespan, etc.) and an increased risk of developing both known and unknown inherited disorders. 

What is the relationship between inbreeding and simple inherited disorders?

Dogs that are related to one another are likely to share similar genetic material. The more closely related dogs are, the more similar their genetic material is likely to be – this is known as Identical by Descent. This similar genetic material could be genes associated with positive traits, but it could also include faulty genes too.

The more closely related dogs are, the higher the risk is that they are both carriers for the same autosomal-recessive conditions (a health condition that can only occur when a dog has two copies of a faulty gene - inherited from both its mother and father). If these two dogs mate, then there is a risk that the puppies will inherit a copy of the faulty genes from both parents and will therefore be affected. This risk of producing dogs affected by inherited health conditions therefore increases with the degree of inbreeding.

What is the relationship between inbreeding and complex inherited disorders?

Some autosomal-recessive conditions can have a large and noticeable impact on a dog's health and welfare (e.g. forms of blindness, epilepsy, etc.), while others may only have a very small, and mostly unnoticeable effect.

As the degree of inbreeding increases, so too does the chance of a dog inheriting more than one autosomal-recessive condition. As the number of these smaller conditions increase, they can have an accumulative effect, leading to a decrease in the general health of the dog, otherwise known as inbreeding depression. This can lead to reduced litter sizes, increased puppy mortality, reduced fertility and a shorter lifespan.

Can DNA testing reduce the risk of inbred dogs inheriting autosomal-recessive conditions?

Yes, but only for the condition tested for.

Remember that every dog is most likely already a carrier for many autosomal-recessive conditions. DNA tests are available for only a small number of the known mutations in dogs, but there are likely to be many more recessive mutations that we currently know nothing about.

It is important that breeders DNA test their dogs they are intending to breed from in order to guard against producing puppies affected by conditions that are known about. It is also just as important to take steps to guard against conditions that cannot be known about. The best way to do this is by considering the impact of inbreeding prior to mating.