Analysis of dog genome assists the understanding of human health
Ever thought of how resembling and how close you and your pet dog can be? Dogs not only share the same air, same water, the same house or even the same bed with humans (Clarke, Toni. 2005), they also exhibit similarities in genes and diseases with humans. Here are some examples of numerous diseases that we share with dogs: Cancer, deafness, blindness, heart disease, epilepsy etc. Scientists therefore believe that decoding dog’s genome will provide helpful information in developing cures for the diseases in both species.
Much work has been done over the past few years to discover which specific gene on a particular chromosome is responsible for a special type of disease. The Dog Genome Project is currently the most popular program carried out at The Broad Institute of MIT and Harvard, which is “part of the National Human Genome Research Institute’s Large-scale Research Network” (National Institutes of Health, 2005). Fred Hutchinson Cancer Research Centre was initially involved, now taken over by the NHGRI.
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This project is applied by scientist as the model system and aims to map and clone the genes of dogs in order for research in cancer and genetic work. Gene mapping is the process that centres the whole genome project. This practise is defined as “the determination of the sequence of genes and their relative distances from one another on a specific chromosome” (The American Heritage(r) Stedman’s Medical Dictionary, 2002). In simple terms, gene mapping is basically “locating genes” (schoolscience) and gene sequencing is just “finding out the nucleotide sequence of their DNA” (schoolscience).
To understand this whole complicated process, we should know first what a gene is. It is a segment of DNA and is this hereditary unit that dictates what organisms are now by manufacturing specific proteins. When genes are joined together in long strings, they are called chromosomes. The most fascinating thing in researching and unravelling information about genes is to discover at which position of a gene on a specific chromosome controls the functioning of an organ, or “behaviour trait” (Matzinger, Polly Dr. 2005) or even causes a disease.
However, there are thousands of chromosomes (strings) in which thousands more units of gene are connected to one another and it is a real challenge to find which exactly is doing what and this is what many scientists are dedicating full-time effort to overcome this confrontation. There are two form of gene mapping: Genetic mapping and physical mapping. In genetic mapping, linkage analysis is the main procedure in evaluating the “relative position of two genes on a chromosome” (Brown, T. A 2002). The positions of genes are referred to as ‘loci’ and ‘genetic mapping’ is basically to find the linked loci where two loci are inherited together.
Independent assortment is the process that separates two loci from different chromosomes. Together with crossing over of DNA, a condition referred to ‘recombination’ occurs, which is the mixed genetic material in offspring but absent in parents. After a numerous steps of working out the parental genotype and progeny genotype, recombination frequency can be calculated: (Number of recombination) / (Total offspring). It is normally presented in percentage so after dividing the sums, times a hundred will give you the answer in percent form.
Recombination frequency is important as it is used to produce genetic maps. The value of frequency will increase while distance between two genes increase. It is dependant on the distance between two loci as well as the chiasma, a site where crossing over of DNA occurs (Brown, T. A 2002). Recombination is less likely to happen if two loci are very close to each other, as chiasma has to be present between two loci. If two genes are linked very close to one another, they will have a value near 0%. However, if they are not at all linked, they would have a number of around 50% (White, Brian 1995).
Physical mapping includes the mapping techniques: Somatic hybridization – the lower resolution method and the Fluorescent In Situ Hybridization, which is the higher resolution method which can ” artificially extends chromatin or DNA fibre” if we are mapping a large region of DNA (Brown, T. A 2002). In The Dog Genome Project, scientists apply the method described above, and specifically use “genetics markers” to identify the genes that causes cancer in animal’s chromosome (Phillips, Melissa Lee 2004). These markers are sequences that vary in separate dogs with identified position on a chromosome.
Scientists then compare and analyse the genome of the healthy dogs and the diseased dogs. If the diseased dogs constantly show a certain marker in their genome while the healthy dog lacks that marker: the probability of the gene that switches on the disease placing nearby the marker is high. Genetic markers would usually contain some defined properties; they are described as “locus-specific, polymorphic and easily genotyped” (Georges, Michel & Coppleters, Wouter 2000) and researchers very much appreciate this tool in tracking down a specific gene’s location.
“Humans and dogs have essentially the same genes,” said by Krestin Lindblad-Toh the co-director of genome sequencing and analysis program from Broad Institute’ (Klaphan, Karen, 2005). This statement can be supported evidently by “their complete genetic map of a twelve-year-old inbred boxer, named Tasha” (Clarke, Toni, 2005). The team at The Broad Institute successfully decoded the whole sequence of Tasha and according to this an association is found “between the DNA of Canis familiaris and Homo sapiens” (Kaplan, Karen 2005). However, there are millions of dogs feasible for this project, why did they choose Tasha?
Simply she fit into the two key concept researchers looked for: First is that the subject has to be in female gender with two X chromosome. Secondly, the subject should show least variation in their genes, so that work can be done with less complication and can therefore minimise error. As described from above, genes are composed of DNA and the subunits that make up DNA are the single nucleic acid with an organic base. There are four different bases of the nucleic acid, represented by letters A, T, C and G. The nucleic acid join to one another, forming a long strand – nucleotide.
When two nucleotides run parallel with each other in opposite directions, the letters (base) will pair up: A pair with G, T pair with C. In human, there are roughly 3 billions of these letters, whereas for dogs they have about 2. 4 billion which is substantially parallel to human’s. According to a LA Times article ‘Genetic Map of Dog may help humans’, dogs have “unusual genetic architecture which made them valuable for medical research” (Kaplan, Karen 2005). Scientist found that there are large block of gene that were the same present in dogs.
These blocks of genes are called haplotypes. Forced mating of dogs with close relatives is one of the reasons behind the occurrence of haplotypes but this is a whole other evolutionary issue to consider. Scientists compare the DNA of abnormal genes of the subjects being experimented to find whether they display a particular trait or not. The team concludes that genes with larger haplotypes are easier to detect. Moreover, “dog haplotypes are 50 times the size of humans” (Kaplan, Karen 2005) which will facilitates the hunting of genes that accounts for the disease.
They also believe that if a defect gene can be detected in dogs, it would take less than a minute to identify the corresponding gene in human. This has a great impact in tracking down the gene that causes diseases in both species. A few experiments reflect this theory. Scientists were successful to hunt down the “cancer-causing gene on canine chromosome 5” (Philips, Melissa Lee 2004). This research was performed by a team directed by Elaine Ostrander, ‘chief of the Cancer Research Institute in Bethesda, Maryland’ (BBC news).
Furthermore, the group compared the location of the canine chromosome with humans and confirms that this region is accountable for human kidney cancer. At Broad Institute, the prime objective is to identify the gene that is responsible for osteosarcoma. This is one of the most frequent types of bone cancer that occurs in human and dogs. Osteosarcoma is usually found “in the long bones of the leg, in the males of both species” (Herskovits, Zara 2005). According to The Boston Globe, ‘Sick as a dog’, larger breeds are more feasible to the disease “such as rottweilers, greyhounds and golden retrievers” (Herskovits, Zara 2005).
Besides, recent researches also reflect that people who are tall are more commonly seen with the disease. Having the complete dog genome is extremely advantageous for scientists because it has simplified many pathways in order to hunt the genes that are responsible for several diseases. Looking at the osteosarcoma case, it provides solutions for the health services to develop “new screening strategies, carriers can be identified” and patients can be treated near the beginning.
Methods of treating both species for example: chemotherapy, radiation or even surgery is hence more operative. Studies demonstrate that more defect genes are recently identified in canines that cause diseases. For example, narcolepsy, the sleeping disorder was found in “Doberman pinschers and Labrador retrievers” (Kaplan, Karen 2005) and epilepsy associating with pointers. In the coming three or four years, more disease genes should be tracked down and cures for diseases is expected to improve and made more effective.
There are a few reasons scientists believe that it is worth spending a lot of time, effort and money to investigate the dog genome project. Mice are the common subjects being tested in laboratories. However, according to ‘The Boston Globe’, results of cancer experiments from mice are artificial and therefore are less reliable. It brought up an issue that laboratories mice did not get cancer naturally; they were “injected with tumor cells, showered with chemicals” thus the outcome does not “reflect what is going on in the body of a person” who has always lived healthily (Herskovits, Zara 2005).
On the other hand, dogs share almost all their lives with human, they live in the same environment as we do and “they get spontaneous cancers the way humans do” (Herskovits, Zara 2005). It is also easier to examine canine’s genetics due to inbreeding. Purebred species are genetically comparable to each other “which makes it easier for researchers to spot genes that are different between the healthy and sick animals” (Herskovits, Zara 2005). Besides, record-keeping for purebred-dogs are better than for humans.
Overall, using canine’s genome as a model system hopefully has provided a framework of what sort of work geneticists and scientists had been undergoing. In the coming future, researchers are planning to pin down more and more of the disease gene especially the caner-causing gene and genes that causes many inherited diseases in canines and humans. Thus better medication and health services can be provided to the affected patients in both species.