Primer on Canine Genetics
The following article is reprinted courtesy of the National Human Genome Research Institute. It gives basic information on DNA and the methods used in its sequencing, and was not written as an all-encompassing treatment of genetics.
What is the canine genome?
A dog’s body contains trillions of cells. Most of these cells contain a nucleus (red blood cells do not have nuclei). Each nucleus has 38 pairs of chromosomes, formed during conception when 38 individual chromosomes from each parent come together to form the new offspring. DNA (deoxyribonucleic acid), the “molecule of life” is the chemical which makes up each of these chromosomes. Every cell contains chromosomes made from DNA, the building blocks of life.
The 38 chromosomes are made up of thousands of genes, which define the traits and characteristics passed down from parental DNA. The term “canine genome” refers to all of the genetic code, including all of the genes found in the canine. There may be anywhere from 20,000 and 200,000 canine genes, and so far only a few hundred have been identified. Genes are difficult to locate because they are found hidden in the DNA across the 38 pairs of chromosomes.
Inside the cell nucleus, genes are used in cells to make proteins and it is these that define individual characteristics. They are the instructions which lead to a black coat color, or a brown coat color; long ears or short, and in some cases, whether a dog is susceptible to diseases such as cancer and immune disorders.
DNA itself is made up of very small chemical components called “nucleotides” or “bases” of which there are only four different types, labeled A, C, G, and T (abbreviations for adenine, guanine, cytosine and thymine). All species use this same four-letter code and dogs have about 3 billion pairs of nucleotides in each cell. A gene, which may be as short as a few hundred bases, or as long as a million, is simply a string of these nucleotides (GGAAACCTGGTATA is an example). The number and length of this sequence of bases determines how the gene will function in the body. It is a very precise code, and a mistake in even a single letter of the DNA code can have disastrous consequences in the health of your dog.
Locating Genes by “Gene Mapping”
Of course, if were able to find these mistakes in genes, we must first find which genes control what, and even before that, we must know where they are. But where to start?
You see, not every piece of DNA in the canine genome encodes a gene. Some of it is so-called “junk DNA” – sequences of DNA that are disposable and do not encode for proteins – which is scattered throughout the genome, blending in with the important gene-encoding DNA. The first task of scientists then, is to find the positions of the genes which are used to make proteins, and to ignore all the non-coding pieces.
In 1971, when scientists devised a method to cut large pieces of DNA on each chromosome in to smaller, more manageable pieces, the job got a lot easier. Within each of these smaller pieces, scientists were finally able to locate the regions containing genes. As the position of more and more genes were found, a “genetic map” was constructed which showed the positions of the genes relative to each other, and relative to the ends and center of the chromosomes. The science of locating these genes is called “Genetic Mapping” and although we now know the location of many genes, the map is far from complete. The Canine Genome Project is working to fill in the holes, to produce a complete map of the canine genome. [Note: this article was written before the canine genome sequencing was completed. – GZ].
Sequencing the Genome
Gene sequencing gets right to the heart of the genetic code, deciphering the exact sequence of lettered bases which compose a gene. As we mentioned earlier, there can be millions of these bases in a gene and so in the past, this process has taken a number of years to find the code for each gene.
But over the past 30 years, scientists have made some remarkable advances in gene sequencing technology. The methods are the same as they were in the beginning, but now it is possible to determine genetic sequences using machines. These automated sequencers allow scientists to learn more about canine genes, faster than ever before. And now, because of these advances in technology, scientists around the world are working towards a day when every gene, on every chromosome will be sequenced. This is one goal of the Canine Genome Project.
Finding Genetic Mistakes
After a genetic sequence is known, the road to a better world seems simple. Find out which dogs have mistakes in their genetic sequence, and then correct the mistake! But in most cases, we don’t know how the gene works or what kind of protein it makes.
Most genes control a number of functions within the dog. And more often than not, how one gene is expressed (turned “on” to make proteins) can have a direct effect on how other genes function. To make matters even worse, some mistakes in the code may be disastrous, and some may have little or even no consequences. It is a complex puzzle to solve.
With the diversity of the canine genome, different breeds may have different chances of genetically having a disease state. Understanding these differences in disease profiles can aid the discovery of complicated genetic puzzles as many breeds have known disease likelihoods and known multi-generational pedigrees. One goal of the Canine Genome Project is to better understand these “inter-breed” relationships so that we can more quickly find genes and genetic code effecting disease states.
Genes and Cancer
Cancer is a genetic disease, but not all genetic mutations are passed from parent to child. Throughout a lifetime, the cells in your dog’s body are capable of undergoing genetic mutations in their DNA. Over a lifetime, these genetic mutations can build up. If a single cell gets enough of them and if they are located within a few very sensitive genes, it may begin to grow out of control, and stop performing the function it was supposed to perform. A cell like this represents the beginning stages of cancer.
Typically, when a dog is diagnosed with cancer, this single cell has grown into a mass of perhaps millions of cells, all of which contain the genetic mutations of the original. They may move to other areas of the body to metastasize and cause a tumor in a totally different organ. Modern cancer therapy aims to rid the body of every single one of these mutated cancer cells, no matter where they lie, since a single remaining cell may well cause the cancer to recur at a later time. Radiation treatment is usually used as a “local therapy”, that is directed at killing cells within the tumor site itself. In a similar vein, surgery is often used to remove the tumor itself. Chemotherapy, however, is known as a “systemic therapy”, because it aims to kill those cells which have wandered from the original tumor site, whether residing in the bloodstream or lodged within another organ. And while there are numerous cancers where these methods of treatment are highly successful, there is still hope that we can do a better job.
Genetic science hopes to augment and ultimately replace current cancer treatment protocols. Indeed, one of the most exciting possibilities lies in the prevention and detection of cancer. Once we know what the mutations which lead to cancer are, all we have to do is find out if a dog has them. And initially knowledge of specific dogs with cancer and/or dogs carrying cancer genes will allow breeders to modify their breeding programs so that these dogs are no longer passing on their genetic information. And someday, it may be possible to use gene therapy to replace disease genes with normal genes.