The Canine Genome: Instruction Manual

We live in an age that is exploding with knowledge and information. Genetics is an area with exponential growth in recent years, and much of this is due to recent technological advances that have allowed for the entire genome of many species, including dogs, to be deciphered. More than 500 hereditary disorders have been described that affect dogs, necessitating an increased understanding of the canine genome to improve the health of dogs. Now that we have mapped the complete dog genome, genes involved in both disease and desired traits can be identified much more quickly. This article provides a brief introduction to the canine genome and how scientists use it to study canine hereditary diseases.

Does this thing come with instructions?

The phrase "canine genome" refers to the complete DNA makeup of a dog. DNA is a unique language comprised of four letters (abbreviated A, C, T, and G), which are actually nucleotides (or bases). The particular order of these bases is extremely important. This arrangement of the DNA determines which areas are recognized as coding or non-coding. Coding sequences, known as genes, carry instructions for making products that determine breed characteristics (height, eye color, and fur length, for example), how the body responds to infection, and behavior. Genes are arranged in a linear fashion on structures called chromosomes. Genetic diseases are caused by changes in the sequence of DNA which alters the product or activity of a gene.

Some assembly required

Imagine a library: a large room of bookshelves, with many books on each shelf. The genome is a library - within it is all the information to build a dog. Continuing this analogy, chromosomes are like bookshelves: large structures that contain a diverse collection of books. Each book is located at a precise location within the bookshelf. This is referred to as a locus, or place on a chromosome. Each book represents a gene. In some places, books of the same subject are clustered together, but in other places, books appear to have been randomly shelved. Some books are long novels, and some are short stories. Within the books, there may be many chapters or a single chapter. On every page, however, there are letters that comprise the words that tell the story. These letters are the nucleotides - the basis of genetic vocabulary - and there are only four.

The canine genome has approximately 2.5 billion bases (letters), divided among almost 20,000 genes (books), across 39 chromosomes (bookshelves).  

AA batteries necessary

Every cell in the dog actually contains two copies of the entire sequence of DNA. This is because at fertilization, when an egg and sperm fuse to create an embryo, the new puppy will contain the complete genome of both the dam and the sire. This means that at every locus, a dog has two bases - one on the maternal chromosome (from dam) and one on the paternal chromosome (from sire). So our genetic “library” has now doubled to 5 billion bases, across 78 chromosomes.

When scientists report results for genetic tests, they are sometimes reported as A/A or A/G. This is the individual dog’s genotype at a specific locus. A genotype is comprised of two alleles, or forms of a gene. Each parent contributes one allele, thus a genotype contains both the maternal and paternal alleles. Sometimes the alleles are the same (both sire and dam gave As) and sometimes the alleles are different (for example, sire gave A, dam gave G).

Use caution when operating

The complete sequence of the canine genome was revealed in 2005. Sequencing efforts began in 2003 with a female boxer named Tasha, and the cost of the project was $30 million. Having the sequence – the specific order of the 2.5 billion As, Ts, Cs, and Gs – allows researchers to examine coding and non-coding regions of DNA, determine the number of genes (approximately 20,000), and compare the canine genome to that of humans and other species. Knowing the similarities among species has propelled advances in understanding which genes are involved in canine phenotypes and disease.

One major resource from the sequencing of the canine genome was the identification of single nucleotide polymorphisms (SNPs). A SNP (pronounced "snip") is a change in base sequence, for example, instead of an A, the base is changed to a C. More than 2.5 million SNPs have been identified among dogs. There is no cause for alarm: most of these changes do not cause disease. SNPs do not typically affect gene function, and are considered "silent" changes.

SNPs are used in research as genomic markers, like call numbers in a library. By examining these markers spaced throughout the genome, researchers can "browse" the genetic library and look at specific locations. The reality is that scientists are only beginning to understand what the 20,000 genes actually do, so determining genetic causality – for desired traits or disease – involves looking for patterns between affected and unaffected dogs  and reducing the investigation to a small, manageable section of genes by the use of SNPs. If a similarity is observed for a particular SNP among affected dogs, the surrounding genes can be examined as candidates for causing the trait.  Many of the recent projects funded by the AKC CHF are based in part on genome wide studies using genomic markers, such as SNPs, to identify regions of chromosomes that may contain the gene(s) that cause disease.

It’s all about the dogs…

More than 45 million households in the United States own a dog. The yearly expense for a dog has been estimated at $1500, with more than half of that going towards veterinary care^*. This amount includes visits that may include diagnostics and treatment for complex diseases such as cancer, epilepsy, heart disease, and autoimmune disease. By supporting canine genetics research, owners can help scientists better understand the diseases that affect their dogs, which in turn will support the development of tests to detect disease early and improve therapies to treat disease. The goal of this research is to help breeders and owners to have healthier, happier dogs and prevent the suffering associated with hereditary diseases.

^*Statistics from 2009-2010 American Pet Products Association National Pet Owners Survey