Article for Ontario Dairy Farmer
May, 1994

Will Molecular Genetics Revolutionize
Dairy Cattle Breeding?
Part 1: The Mysteries of Genetic Design

John P. Gibson
Centre for Genetic Improvement of Livestock
Animal & Poultry Science, University of Guelph

Breeding of dairy cattle has had remarkable success. But how much do we really understand about the detailed genetic makeup of our cattle?

Dairy cows are dairy cows and not dogs, cats, mice or any other animal because of their unique genetic makeup referred to as their genotype. The genotype consists of around 50,000 to 100,000 individual genes that form a set of complex instructions which determine an animal's characteristics. The genotype is analogous to an architect's plan, or a manual of instructions, that when followed, leads to the construction of a particular building. The genotype of a cow and a mouse, although sharing many common principles, nevertheless are very different, much as the plans for an office tower in Toronto will look very different to those for a dairy farm. And, although the plans for any two farms will look very similar to each other (at least in comparison to the plans for the office tower), subtle differences in the plans describe the unique differences of one farm from another. Similarly, each cow has its own unique genotype, its own set of plans, which determine many of the individual characteristics of that cow, such as her size, shape and colour, how much milk, fat and protein she will give, and so on.

With genetic improvement we attempt to improve cattle by producing a better genotype, a better set of plans. But, we still know very little about how the genotype works. We don't even know exactly how many instructions there are (50,000 to 100,000 genes is a rather vague statement), let alone what most of those instructions say, how they are carried out or how they interact with each other. Since we don't know what the instructions are, we practice selection on the final product, the performance and looks of the cow and her relatives (e.g. sire, dam, sisters). This is akin to deciding on which architectural plans to use based on the looks and performance of the final building. Just as we can choose a house or farm to suit our needs, so we can choose cows, without necessarily understanding the complexities of the design process.

It is here that the parallels with architectural design break down. An architect can attempt to build a better house, one that is more attractive, better to live in, more energy efficient, etc., by utilizing the best instructions from different designs, and modifying other instructions based on their understanding of the physics of building, the cost of materials and the needs and resources of their client. Although errors certainly can and do occur, the form and performance of the final building is fairly well predicted in advance. With cattle breeding, each parent contributes a randomly chosen one-half of their genes (instructions) to their progeny, so that every progeny is unique. We have no control over this process, and do not in any case know what most of the instructions are, so we have to wait until all the progeny are born and start producing to judge the success of this random selection of instructions. The process works, as witnessed by the dramatic changes in performance of dairy cattle over the past 40 years, but it is slow and inefficient. We could probably improve our success by understanding more about the design at the level of the instructions, the genes themselves.

Trying to understand the complexity of genetic instructions is a daunting prospect. Consider the size of the problem. Think of the genotype of a cow being an instruction manual. Each of the 100,000 genes is about 4000 base-pairs in length, each base-pair being a letter in the genetic alphabet. A standard book page with smallish print carries about 4000 letters. So to store this information, a genetic instruction manual would have 100 volumes, each with 1000 pages. On top of this there is a huge amount of genetic material that appears to have no function. For every functional gene of 4000 base-pairs, there are about 40,000 base-pairs of non-functional, nonsense DNA; that is 10 pages of junk for every page of useful information corresponding to a functional gene. Thus the whole genotype is an instruction manual of 1100 volumes, each with 1000 pages, in which for every page of useful instruction, there are 10 pages of rubbish. Moreover, this manual comes with no contents pages, indexes or reference keys, and is written in a highly complex language we are only just beginning to decipher.

Impressive in its complexity, perhaps the real miracle is that all this information is contained in the single copy of DNA passed on from the sire, in the sperm cell, and from the dam, in the oocyte. This molecule of DNA weighs a mere million millionth of a gram. To imagine how small that is, it would take a thousand million million molecules to weigh the same as a litre of milk. How many is a thousand million million? A thousand million million quarters laid end to end would stretch to the moon and back about 5000 times. A politician a thousand million million miles from home would be about twenty times further away than Sirius, the brightest star in the sky (some might argue that this is only a little more distant than Ottawa). Suffice to say, a single DNA copy of the genotype is extremely small and requires the most advanced technologies to even begin to read it.

Every animal has two copies of the genetic instruction manual, and all animals have the same basic instruction manual, except that there are several different versions of each page in the population. This means that, for a particular animal, page 42 in one copy of Volume 10 does not necessarily read exactly the same as the other copy of page 42, Volume 10. And, page 42 from one animal is not necessarily identical to page 42 from another animal. Because there are several variants of virtually every page, any two animals chosen at random will differ at several thousand pages in the manual, and no two animals have exactly the same set of instructions. (The only exceptions to this last rule are identical twins and clones which carry identical copies of the whole genome.)

Most of the variations in pages (genes) between animals are relatively minor having no real effect. Some are sufficiently important to have a small effect and a few have large effects. We have long been able to follow the effects of those few variations in pages of instruction (genes) with large effect, such as the polled gene (causing lack of horns in some cattle breeds), the BLAD gene (bovine leucocyte adhesion deficiency, causing lack of vigour and early death in calves) and the double muscled gene (causing massive extra muscle growth in some beef breeds). But, most of the genetic diferences we see between animals are due to the many variations in individual genes that each have relatively small effect. A recent massive expansion in the science and technology of molecular genetics is now providing techniques to find and follow genes of smaller effect and is providing insights into the genetic architecture of animals. In subsequent articles we will look briefly at some of these technologies and how they might be of use in dairy cattle breeding.