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Animal Productivity and Genetic Diversity

07 September 2009

Possibilities through cloning and transgenic technology have both their strengths and weakness as well as technological limitations, writes TheCattleSite Junior Editor, Charlotte Johnston.

However, perhaps the most significant hurdle with regard to their future use, is the lack of public understanding and acceptance, according to a report written by the Council for Agricultural Science and Technology (CAST).

Cloning is a reproductive tool that can be used to narrow or broaden genetic diversity. Cloning can increase the frequency of superior production traits by copying the genotype containing the genetic information. This is most beneficial for breeding stock, particularly as cloning allows the genetic gain to be achieved in a shorter time span than other approaches.

The most common livestock cloning method, somatic cell nuclear transfer (SCNT) can increase animal production efficiency by creating groups of animals with desirable traits. On top of this, nuclear transfer technology can help maintain and increase the genetic diversity of animals, aiding the survival of endangered breeds. To increase this genetic diversity it can recreate reproductively competent copies of animals that had perhaps been incompetent or made incompetent early in life.

Conventional reproduction increases genetic variability through mixing parental genetics. Geneticists can use the genetic variability in their breeding strategies. Selective breeding then allows those superior genetic traits to be generated.

Most genetically improved traits in livestock can be attributed to the means that allow geneticists to predict the potential genetic merit of offspring.

Selective breeding does however have its limitations. It relies almost exclusively on the existing genetic variation in the population - if this variation does not exist it is not possible to select it. Selective breeding does not allow the geneticist to improve existing traits but more to select the best traits and put them together.


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"Genome - The complete set of genetic information for an individual. It is a set of heritable information passed from one generation to the next, encoded by DNA molecules."
Council for Agricultural Science and Technology

Transgenic technology offers potential solutions to some of the limitations of selective breeding, whilst also increasing genetic diversity.

New genetic information can be introduced precisely into the desired location in a genome, through the use of well-established recombinant deoxyribonucleic acid (DNA) protocols.

Perhaps the most important feature of transgenic technology is its unique ability to use genetic code information from almost any source. The code which allows DNA to spell out genetic information is universal. This allows genetic information from bacteria to be introduced into and processed correctly by a cow or another animal. The ability to cross species barriers potentially allows the geneticist to use any desirable genetic solution that nature has devised.

CAST define 'cloning' as genetic identity, either in the context of making genetic copies or having two or more genetically identical animals.

How Does SCNT Work?

SCNT uses a body cell rather than an embryonic cell as a nuclear donor. The DNA in the nucleus which is transferred into an egg (oocyte) requires reprogramming. Little is known about how this reprogramming occurs except that it can often go wrong. This is because the one-cell embryo normally programmes sperm and egg DNA, not DNA from somatic cells.

Currently all SCNT procedures result in 90 per cent of embryos dying. (For perspective, embryonic foetal death rates are normally 20 to 30 per cent with farm animals and seem to exceed 50 per cent in women.)

Despite the weeding out of problems throughout the pregnancy, some abnormal animal pregnancies do go to term with conventional methods and with SCNT. The incidences are much higher with cloning and seem to be caused by abnormal placentas - the foetuses and newborns are mostly normal but have problems because of development and birth. Fetuses may die or offspring is born abnormal. This is called abnormal offspring syndrome (AOS) and includes conditions such as hypoxia (a deficiency of oxygen in body tissues), hypolglycemia (low blood sugar levels) and most commonly oversized offspring. The majority of these incidences correct themselves after special care is given and offspring develop.

These embryonic and foetal deaths which occur with SCNT is a major reason for low success rates and high costs of the procedure.

Safety of food from clones

For those without the knowledge of cloning, the idea creates an uneasy reaction. The US Food and Drug Administration have addressed concerns of food safety in a recent report, Animal Cloning: A Risk Assessment.

The report indicates that milk, meat and other products from cloned animals are as safe as those from non-cloned animals. The study does highlight the struggle to achieve acceptance of cloned products in the food supply. Although no study can evaluate all cloned animals exhaustively, there is no reasonable scientific evidence to suspect that food products from any cloned animal would be less safe than those same products from non-cloned animals, regardless of species.

Clones for Breeding Purposes

The report by CAST states that current costs for cloning cattle exceed $10,000 per animal produced. Due to this and some inefficiencies of cloning, mass producing clones for meat or milk is unprofitable and likely to remain so for many years.

Other applications do exist that already would be profitable for breeding purposes. For example cloning a bull worth more than $100,000 for the value of its semen to use in conventional breeding. Cloning of genetically valuable animals will also be beneficial in cases of premature death.

Another use would be to breed from an animal that is castrated. Once the animal has been killed and the quality of beef attained, cloning a fertile copy (cells must be collected within a day of slaughter) will allow that animal to sire superior beef animals.

When discussing cloning, concerns arise with regard to inbreeding and narrowing the gene pool. Cloning is a genetic tool and can be used to narrow or broaden the gene pool. Effectively with selective breeding, the gene pool is decreasing as undesirable traits are removed from the breed. With cross breeding, the genetic diversity of the hybrid vigor is increased, however the genetic diversity of the population decreases.

If cloning were a routine and relatively inexpensive tool like artificial insemination, there would be potential to increase the genetic value of a population for traits suitable to producers and consumers by up to 30 per cent in one generation. Such an increase through conventional methods would take five or six generations.

It is important to remember however that this is a "one-time boost'. No matter how many times one clones a particular animal, the clone in theory, will exhibit the same incremental genetic gain. The 30 per cent boost in genetic value cannot be built upon by another 30 per cent in the next generation. One returns to the non-cloning rate of genetic progress.

Cloning for Direct Food Consumption

For producers and consumers, uniformed animal products would be desirable - with regard to quality and efficiency, for example cloning could speed the introduction of a desirable trait such as reduced incidence of Escherichia coli into the cattle population. However it would not be possible to produce one type of cattle to fit all conditions, subtropical, Western range land etc. as well as an ideal carcass for steak, hamburger, and milk for cheese production. This is because the ideal carcass for each of these is different and so dozens of clonal lines would be required for optimal cloning commercialisation for food production.

Transgenic animals

Sometimes the only difference between a transgenic animal and a cloned one is a single gene. Sometimes a transgenic animal is made using cloning technology. An animal can be a clone, however, and not transgenic or can be transgenic without being a clone.


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"Pronuclear microinjection - injecting a solution containing the new gene into a recently fertilised egg"
Council for Agricultural Science and Technology

A transgenic animal is (1) one into which a new gene has been introduced by human intervention, or (2) an “organism, with the exception of human beings, in which the genetic material has been altered in a way that does not occur naturally by mating and/or recombination”.

The new gene is intended to alter some physiological characteristic of the animal, such as increased resistance to disease, enhanced carcass quality, improved feed conversion efficiency, increased food safety, or decreased environmental footprint.

There are a number of ways by which the gene can be transferred, although almost all approaches introduce the genetic information when the embryos have only a few cells. Two common methods are pronuclear injection (the first successful method) and a recently developed method using lentiviruses.

Both of these methods and others have weaknesses.


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"Lentiviruses - a virus carrying a 'blueprint', genetically engineered to carry the new genetic information to infect early stage embryos
Council for Agricultural Science and Technology

Firstly, genes introduced by these methods are inserted randomly - and depending where they land can have negative consequences.

Secondly, when inserting viruses it can be hard to keep track of where the gene was inserted into the genome, particularly in later generations.

Cloning may help resolve these issues. One application of SCNT cloning is as a gene transfer technology. These gene transfer techniques provide a means for genetically engineered precision. Thus, it is possible to direct the new genetic information to the exact desired location in the genome of these cells.

Using cloning technology as a means of producing a transgenic animal provides a method for genetic engineering to be done with more precision than could be achieved by the original transgenesis techniques. Furthermore, cloning technology is more efficient than many other means of producing transgenic farm animals, resulting in the use of fewer experimental animals to achieve success.

Disease Resistant Transgenic Animals

Perhaps one of the most appealing use of transgenic technologies in farm animals is the ability to combat diseases. Infectious disease adversely affects livestock production and animal welfare, thereby affecting a community’s sustainability and competitiveness. The costs of existing endemic diseases are estimated at 17 per cent of turnover of livestock industries in the developed world and 35 to 50 per cent in the developing world. Individual diseases, such as mastitis in cattle, can have multibillion dollar impacts. Epidemics, particularly in developed countries, can incur further costs and have profound impacts on the rural economy and on public confidence in livestock production.

Transgenic technology is delivering animals that challenge both commercial attitudes and public opinion. These technologies will lead to new opportunities for diagnosis, intervention, and selective breeding of animals for disease resistance. The combination of these technologies with traditional disease control measures should allow for more effective and sustainable animal disease control.

Transgenesis offers a method to prevent disease by attacking the pathogen. This would mean attacking the identified cells, which would have to be nonessential to the animals existence, but which are essential for an animal to become infected by a particular disease.

For example, the development of BSE requires the host animal to have the prion protein “prp” in its cells. But transgenic cattle have been generated that lack this protein completely, so these animals are resistant to transmissible spongiform encephalopathy development and do not show any disease symptom. The initial analysis of a number of parameters—including immune function, behavior, growth, and reproduction—indicates that these animals are otherwise normal.

Another way to tackle disease would be to create animals that are better able to combat or resist infection. This would involve enhancing the immune response of an animal, conferring additional innate protection, or blocking the route of pathogen entry into the animal.

Transgenic cows have been generated that have elevated concentrations of the anti-microbial protein lysostaphin in their milk. This enzyme destroys one of the bacteria which cause mastitis and as result these transgenic cattle are much less susceptible to the disease. Decreasing the incidence of mastitis in the US dairy herd alone will provide multibillion dollar savings and will improve the well-being of these animals.

These transgenic disease prevention policies would need to compete on a cost - benefit basis against other disease prevention strategies. Transgenic strategies can provide novel intervention approaches not possible through established prevention schemes. There are current concerns regarding the extensive use of antibiotics in animal agriculture - possibly speeding up the development of antibiotic-resistant organisms. Genetically modified animals with better ability to combat disease will require less antibiotics and contribute to a more efficient food production with less environmental impact.

Transgenics for Improved Food Safety and Quality

Current production systems provide safe animal food products with good nutritional qualities, but there is room for improvement. Precautions often are taken postharvest (e.g., the pasteurisation of milk and vacuum packaging of meat) to ensure the safety of many food products and to preserve their quality. Transgensis could be used to improve food safety and quality preharvest.

Modified milk protein: An example of this would be through milk production. The shelf life and stability of milk and milk products is important for food safety and quality. Milk proteins and fat globules break down with time, thereby decreasing the quality of the product. Bacteria naturally present in the milk and those contaminating the milk also can affect its shelf life.

One option to prolong milk's shelf life is by enhancing expression of antimicrobials. Lysozyme is a naturally occurring antimicrobial found in the milk, saliva, and tears of all mammals as part of the bacterial innate defense system. Concentrations of lysozyme in the milk of dairy animals are 1,600 to 3,000 times less than those in human milk. By increasing the concentration of lysozyme in dairy animals research has shown that milk could be left at room temperature for at least two days before bacterial growth was detected.

Improved nutritional quality: Animal food products can contain high concentrations of saturated fatty acids which have been associated with cardiovascular disease and high blood pressures. Fish is known to contain high concentrations of omega-3 polyunsaturated fatty acids (n-3 PUFA) which prevent cardiovascular disease and promote human development. Livestock have high concentrations of n-6 PUFA from which n-3 PUFA can be derived in plants, however they lack the enzyme to convert it.

Transgenesis can generate livestock with the enzyme, enabling this conversion, resulting in meat with improved nutritional quality.

Transgenesis also holds the potential to create milk for people who are lactose intolerant. Low lactose milk can currently be created by postharvest treatment, although it is expensive and time consuming. With this technology, lactose could be expressed in the mammary gland and could catalyze hydrolysis of the lactose after it is secreted in the milk, without disrupting milk production.

Could Transgenics Decrease the Environmental Impact of Agriculture?

There are a number of ways by which animal production has negative impacts on the environment including excreting phosphorus, nitrogen, and metals, generating greenhouse gases and requiring land for cultivation of their feeding.

Transgenic technology may offer solutions to these for example by improved feed efficiency through growth-enhancing genes. This would result in fewer resources been required such as land, fertiliser and energy for cultivation. Improving the digestibility of glucans in barley, oats and rye would also improve feed utilisation and use fewer resources. Transgenesis can also be used to reduce phosphate excreted thus reducing pollution of water courses. Most phosphate in feed stuffs is in the form of phytate, which is non-digestible resulting in 60 per cent of phosphorus in feed stuffs ending up as manure. Research has been carried out with transgenic pigs allowing the phytate to be digested and resulted in a 75 per cent reduction in fecal phosphate.

Can Transgenics Increase Production Efficiency?

With the application of transgenics, it is possible to improve the quality of meat, milk and fibre components.

Initial transgenic livestock studies focused on modifying body composition for increased meat production by stimulating growth rates with the introduction of genes for these growth factors, including growth hormones. It is important to note here that little research has been carried out on livestock, the majority of tests been carried out on mice and so further knowledge is needed.

The growth hormone transgene had disappointing effects only slightly increasing growth rates and decreasing carcass fat by as much as 80 per cent at market weight. Along with this were side effects such as lameness, susceptibility to stress and reduced fertility. More desirable effects have been achieved with more control of the transcriptional regulation of the growth hormone transgene, such as targeting growth factor expression to skeletal muscle. These limitations in domestic animals are likely to continue.

An alternative strategy which is under research would improve growth performance and offer greater control through direct interference with regulators of skeletal muscle growth. The functional loss of myostatin, a negative regulator of muscle growth was shown to result in a 20 per cent increase in muscle mass in some double-muscle beef breeds.

Because these known double-muscling breeds are associated with major calving difficulties and resulting welfare concerns, transgenic technology could provide the opportunity to limit the myostatin-related effects to only postnatal muscle growth.

There are further possibilities to improve milk production, not only through added nutrition but by specifically targeting milk protein. Research shows that when the milk protein fraction 'casein' was increased by adding additional genetics, there was a size reduction in micelles, which has been associated with heat stability and improved cheese manufacturing. Therefore there is the possibility to alter milk composition with modern dairy cows within a single generation.

Conclusion

This report shows that cloning and transgenesis have their strengths and weaknesses. Cloning can be used to make rapid genetic gains, but eventually breeders will have to rely on conventional breeding to create new genetic variation from which the next generation of elite animals will be selected. Transgenic technology can be used to address a variety of problems and introduce new characteristics into the gene pool. However, the technology has not yet been applied to manipulate complex traits that are controlled by multiple genes.

It cannot be argued however that both tools will have a positive effect on enhancing agricultural production, the greatest hurdle is however the lack of public understanding and acceptance.

So far, no hazards have been identified that would constitute a risk to consumers. Therefore, the risk currently perceived by consumers likely is associated with the unknown rather than with a genuine hazard. Recently, regulators have begun to fashion a framework designed to assure consumers that a strategy for dealing with cloning and transgenesis is being developed. A regulatory process in which consumers have confidence and with which biotechnology companies can afford to comply must be in place for transgenic technology to be applied to livestock.

Some of the most compelling projects enhance animal well-being and decrease the environmental impact of animal production.


September 2009

Further Reading

- You can view the full report by clicking here.


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