Murray E. Fowler, DVM
A genome is the sum total of all the genes, DNA and genetic information of an animal, neatly packaged in two distinct copies (one from each parent) in every cell of the body. While the term is of relatively recent usage in the scientific literature, its parent genetics has been around since the mid 1800s when Gregor Mendel, an Austrian monk and the father of modern genetics established Mendelian ratios by observing the results of breeding pea varieties. He established what we know today as dominant and recessive traits which have played such a prominent role in animal breeding, hair/fiber coat colour selection and dealing with hereditary defects..
When the author was a university student, genetics was studied by counting traits in fruit flies. A total revolution in genetics has occurred during the intervening years with the use of sophisticated chemistry, molecular biology and high technology.
Before delving into the intricacies of the genome, let?s consider how we have been using DNA technology in managing llamas and alpacas. In 1987, the use of blood types became a tool for parentage verification. By 1998 this method was replaced with the use of microsatellite markers (a DNA technology) which provided greater reliability, up to 99.5 % accuracy.
The microsatellite marker technology is also used to assist in establishing the heritability of a trait and even species identification or relatedness of individuals.
Why should the alpaca and llama industries be concerned about genetics in general and the genome project in particular? Traits that are known to be influenced by heredity include conformation, physical and physiologic traits. Of importance in the veterinary aspects, the susceptibility and/or resistance to infectious and parasitic agents are influenced by heredity.
Congenital defects are of concern to all animal industries and camelids seem to have more than their share of these conditions. Some congenital traits may be caused by physical and chemical factors, but the majority are caused by genetic traits that have gone awry, yet none of these have been positively identified as being passed by genes. These and other factors may be addressed by the advances being made in camelid genetics.
An historic event in the camelid world, the first International Workshop on Camelid Genetics convened in Scottsdale, Arizona, USA. March 22-24, 2008. The purpose of the meeting was to bring together experienced basic scientists from the National Institutes of Health, academic geneticists, clinical veterinarians, veterinary pathologists, owners/producers and organizational administrators to share thoughts and opinions on camelid genetics. The workshop was international in scope with participants from Australia, Canada, Peru and the United States. The disciplines represented included geneticists, molecular biologists, giants in the field of genomic research, clinical veterinarians, pathologists, academicians and fiber specialists.
The workshop was sponsored by the Alpaca Registry Inc. (ARI) and the Alpaca Research Foundation,(ARF). The timing for such a meeting was thought appropriate because the alpaca has been chosen for genome sequencing. The alpaca joins a short list of other species such as yeast, several plants, mice, rats, dogs, cats, horses, cattle and recently, humans, for which genomes have been sequenced.
The significant factor in the success of the meeting was that everyone listened to each other. No egos burst forth. Did differences of opinion crop up? Yes indeed, but courtesy prevailed and both formal and informal discussions were highly fruitful.
What was necessary for genetic research to blossom? First and foremost was a knowledge of the chemical structure of DNA, culminated by the work of Watson and Crick in 1953, who established the double spiral helix of DNA. Also crucial to the advance of the genome was the development of computers (first the mainframes in the late 40?s and 50?s and ultimately the personal computer which came on the scene in 1981). Integral to the computers was the instrumentation to automate DNA analysis and the software to manipulate the data.
The veterinary clinicians in attendance at the workshop sought answers for questions such as, ?How can we identify the heritability of congenital defects?? ?Can we determine if a parent is a carrier of a hereditary defect?? ?After the alpaca genome is completed will we be able to manufacture vaccines that are safe and effective against infectious diseases of camelids?? The answers were qualified yeses! Does more research need to be done? Yes! Will it cost money. Yes! Will it take time to solve the clinical problems? Yes indeed!
In general, congenital defects are more common in camelids than in other livestock species. Although over 100 such defects have been reported in camelids, none have been subjected to enough scientific scrutiny to be certain that they are inherited. Many of these defects are known to be inherited in two or more other species of animals and may be presumed to be inherited in alpacas and llamas, but it is not known to be a certainty. Management of camelids requires knowledge of which defects may be inherited and how the process works.
Is it important for the camelid industry to know if a trait is inherited and how it is inherited? Absolutely!! It is economically important to the camelid industries and may obviate the heartache that goes with waiting for eleven months only to see a deformed, non-functioning cria.
After the basic principles of genetics were presented, attendees heard how the tools that are already known and used in cattle may be applied to alpacas and other camelids. Reproductive anatomic and physiologic traits are known to be controlled by genetics. Unfortunately, there are several anatomic and physiologic (hormonal) defects that interfere with the reproductive process and prevent optimal birthing of healthy crias. Many of these traits were described and the discussions that followed indicated that genomic research may be useful to identify and solve these problems.
A special congenital defect called choanal atresia was brought to the fore as a priority for genetic problem solving. Prior genetic research has been unsuccessful. The genomic era may enlighten us.
At least one of the traits possessed by camelids may have relevance to human medicine. Camelids maintain a ?normal? blood sugar level that in humans and other animals would be considered to be diabetic. Yet alpacas and llamas suffer no apparent ill-effects of this hyperglycemia. It might be important for researchers investigating human diabetes to know how camelids remain healthy while maintaining such high levels and why? Genetic technology is helping to solve these kinds of problems in other species and there is every reason to believe that it will do so in camelids.
Several of the research reports presented at the meeting were preliminary such as suri genetics using microsatellite markers, pedigree mapping and parentage verification for pedigree studies. The completed alpaca genome will add more sophisticated tools for studying these practical challenges.
Genetic studies have been conducted for decades. It would be unwise and incorrect to suggest that such things as Mendelian genetics will be completely superseded by genomic studies. For instance, colour inheritance may be studied by simple inheritance as reported at this meeting. Likewise, Mendelian principles have been utilized in camelids for selecting breeding animals and herd management.
Early in the development of the camelid industry in the private sector it was deemed necessary to develop a method of verifying the parentage of a cria. In 1987 such a test was developed using the variation of proteins in the blood of each individual. For several years, serologic blood type testing was mandated for animals to be registered in either the llama or alpaca registries in the United States. In 1998, advances in DNA technology made it possible to verify parentage by that means.
Fibre is one of the easiest conformation traits that can be improved upon by genetic selection. Presentations were made on qualities that can be measured. Fiber colour is important and we were informed as to the state of current knowledge of color genetics, and how the genome project may help in the future. There is still much to be learned about fibre and knowing the location of genes on the chromosomes will further the industry?s ability to produce a still higher quality of fiber. Suri genetics were also discussed.
Infectious diseases are an ever present threat to all animals. While alpacas and llamas have few unique diseases, they seem to be somewhat susceptible to diseases that generally affect only cattle, sheep or horses. Some of these diseases are transmitted by insects and ticks. Camelids may develop a titre to these organisms and may or may not develop clinical disease. Only in rare situations may a camelid become a source of infection for other livestock species. It would be important to know why camelids allow these infectious agents into their bodies and why they react immunologically to the antigen and produce antibodies or develop the clinical disease.
Likewise, it would be desirable to show genetically that camelids are resistant to many of the diseases that are listed by regulatory agencies. It would make camelid owner?s life less complicated when traveling to shows and sales if camelids were not labeled in the same category as ruminants.
We still do not have the ability to determine scientifically whether or not an individual is a hybrid. That may change when the genome project is completed.
It is not necessary for camelid owner/breeders to know all the chemistry and physics associated with camelid genetics. Hundreds of genetic scientist have devoted their entire careers to sorting out the most detailed secrets of DNA. The camelid industries are in a position to benefit from those studies and camelid owners should be grateful that the alpaca was chosen as worthy of study. Much of the information obtained will have direct application to all camelids.
It became evident during this workshop that teamwork is essential for solving problems. Researchers in the camelid industries need to work closely with geneticists to identify conditions that need attention. Genetic research is expensive. It is estimated that bringing the human genome project to completion cost three billion dollars and was heralded as one of the great feats of modern science. The human genome project took 16 years to complete from the time it was first proposed until the first draft was reported in 2001. The development of automated systems has cut the time and expense of such research to a fraction of that necessary just a few years ago. The alpaca genome project was completed in less than three years.
Part of the expense of completing the alpaca genome project and applying it to practical day to day problems must be supported by the industries that will benefit from the research. Furthermore, associations must be become knowledgeable about what has been done, what is being done and what needs to be done in the future. To that end, I have appended the titles of two books that are suggested reading, but these books should be required reading for serious owner/breeders and clinical veterinarians. It may also be necessary for some politicking to help raise funds to support this vital research.
The industries should support the alpaca genome project philosophically, morally and financially. In order to do that individuals should be conversant with basic principles. We don?t need to be geneticists, but we do need to be able to talk to them. We need to understand some of their terms. I have included a glossary of some terms that may be encountered when reading about genetic articles in our journals.
What of the future? Those in attendance agreed to prepare some documents that will outline the need for investigation. Task forces were assigned to people with an interest in camelids and who are willing to devote time and effort on their behalf. The first international workshop on camelid genetics must be followed by similar gatherings to hammer out specifics and to communicate with others who have similar goals, ideals, experience and expertise.
In conclusion, the value of the alpaca genome projects will allow:
1. determination of what gene(s) control resistance or susceptibility to infectious or parasitic diseases
2.Give us a better potential for herd management.
3. Ability to solve congenital disease riddles.
4. Determine the carrier status of defects.
5. The potential for the production of safe and effective vaccines. With teamwork we can made a difference in the exciting world of camelid genetics
Glossary of selected terms
Following are some terms that may be encountered as you read about camelid genetics and genomics:
Allele ? One of several different forms of a gene. Slight differences may produce changes in the end product of gene function (eye color, hereditary diseases, resistance to a microorganism).
Antibody ? Specialized serum proteins produced when the body is exposed to specific antigens (infectious agents).
Antigen ? Any substance that is capable of inducing a specific immune response that produces antibodies when ingested or injected into the body.
Biodiversity ? The sum total of all life on earth.
Bioinformatics ? The process of using a computer to search through massive biological data bases.
Choanal atresia ? A membranous or bony partition in the nasal cavity. It may occur on one side only or both sides, be complete or incomplete. If complete, the cria is unable to breathe and eat at the same time because a camelid must breath through the nose.
Chromosome ? A linear or circular strand of DNA that contains genes. Each animal has a specific number of paired chromosomes. In the case of camelids 37, or as usually written 2n = 74.
Congenital defect ? Abnormalities of structure or function which are present at birth. Not all of these are genetic defects as other physical, chemical and infectious agents may affect the fetus.
DNA ? An acronym for deoxyribonucleic acid. It is the genetic material that comprises the genes, chromosomes and the genome. DNA is in the form of a double helix (spiral) as reported by Watson and Crick in 1953.
DNA fingerprinting ? Much like the fingerprint used in human identification, but done with the unique DNA characters for each individual animal. Commonly used in forensic medicine (crime solving).
DNA sequencing ? Establishing the anatomy of DNA by chemical analysis
Gene ? The fundamental unit of heredity. A specific section of DNA within a chromosome. The unit of information in DNA that specifies the translation of a particular protein. Mammals have 20,000 to 35,000 distinct genes in their genome.
Genetic defect ? Sometime called an hereditary defect, Certain genetic disorders may cause serious defects in a single individual, but the disorders will not be passed on to subsequent generations.
Genetic diversity (variation) ? Variation that occurs in a group of interbreeding organisms (camelids) by the frequency of alleles appearing in a population or the frequency of genotypes.
Genetic engineering ? The direct manipulation of genes to alter the physical appearance of an animal.
Genotype ? The entire genetic makeup of an individual.
Genome ? A full-length copy of an individual?s genetic endowment. A genome is the sum total of all the genes, DNA and genetic information, neatly compiled in two distinct copies (one from each parent), in every cell of the body.
Hereditary defect ? A defect that is passed from one generation to the next by the parents.
Hyperglycemia ? An excess of glucose (blood sugar) in the blood.
Immunological ? Pertaining to immunology, the study of all aspects of immunity.
Karyotype ? A microscopic picture of the chromosomes.
Microsatellite ? A stretch of DNA that is repeated several times in a row. All mammals examined so far have 100.000 to 200,000 such repeats. These are located at random throughout a chromosome. The variation in these markers between individuals allows for parentage verification and is a tool in the forensic community for matching blood and semen left at a crime scene. These microsatellite markers are given names and numbers.
Mendelian genetics ? Simple inheritance based on dominant and recessive traits that segregate according to mathematical ratios. Gregor Mendel was an Austrian monk who used plant breeding and direct observation to establish the ratios. He is considered the father of modern genetics.
Molecular biology ? The study of the biochemical and biophysical aspects of the structure and function of genes and other sub-cellular entities.
Phenotype ? The observable expression of the genotype of an individual (structure, color).
Recombinant DNA technology ? A process of finding a gene on a chromosome, snipping it out of its original location and inserting it into a new location (another organism). Currently used in the production of safe and efficient vaccines for animals and humans.
Titre ? The degree of reaction of an antibody when exposed to an antigen. Usually expressed as a dilution 1/50, 1/250 etc.
Suggestions for further reading
For camelid owners and others wishing to obtain a further understanding of genetics, the following books (written for the general public) are recommended.
O?Brien, Stephen J. 2003. Tears of the Cheetah- The Genetic Secrets of our Animal Ancestors. St. Martins Press, 175 Fifth Ave, New York, NY, 10010.
ISBN 0-312-27286-3 (hard cover)
ISBN 0-312- 33900-3 (paper back)
Robinson, Tara Rodden. 2005. Genetics for Dummies. Wiley Publishing, 111 River St., Hoboken, New Jersey, 07030-5774.
Both of these books may be ordered through most book stores using the ISB number. Amazon.com may also be a source.