3.3.6 Epigenetics
Although many medical conditions are the result of gene mutations that have passed from generation to generation, evidence is mounting that the environment can not only have an impact on personal health but can also be conserved in the genes. These environmental “shocks” seem to be capable of leaving an imprint on the genetic material in eggs and sperm, which can pass along new traits in a single generation.
The epigenome sits above the DNA sequence and provides a second layer of information, regulating several genomic functions, including when and where genes are turned on or off. New studies have shown that so‐called epigenetic marks are associated with genes, providing instructions such as telling them to switch on or off. These marks are normal and allow cells to differentiate, but if the marks do not work properly because of an environmental stressor, cancer or cell death might result, and, worst of all, could be transmitted to descendants. So, if some stressor such as a rich diet activates an epigenetic mark, which in turn modifies histones or adds methyl groups to DNA strands, it could result in disease or susceptibility to disease that not only affects the individual but can be passed on to future generations. This epigenetic influence may not even occur equally across both alleles, in some instances depending on genotype and in other instances depending on from which parent the allele was inherited. Nutrition is likely a major factor in epigenetics, and technological advances will likely lead to the identification of nutrient‐responsive genes and biological pathways, important nutrient–gene interactions, and genomic biomarkers of disease [1].
While perhaps not as well known and discussed as the genome, the epigenome is believed to be much larger and more complicated than the genome of 20 000 or so genes. Medications are even available now that exert their effects through epigenetic marks. These developments are bound to assume more significance in the years ahead.
3.3.7 Genetics and Cancer
There is no doubt that many cancers have genetic associations [2] but there is still much to learn about the genetics of cancer. Solid evidence exists that some cancers, such as those associated with dermatofibrosis, have a genetic basis, and a DNA test can even be used for that particular disorder. Pugs are predisposed to viral pigmented plaques, associated with papillomavirus. Lymphoproliferative diseases also appear to have well‐defined heritable risk factors in at least some breeds. In many other instances, definite breed predispositions exist, but in many cases a definitive genetic basis is lacking. In other cases, epigenetics and environmental causes may coincide with genetics to promote cancer. For example, the incidence of transitional cell carcinoma (TCC) has been steadily increasing in dogs over the years, and the risk of Scottish terriers developing TCC is approximately 18 times the risk of mixed‐breed dogs [3]. Further studies have suggested that this breed‐associated risk may be due to differences in pathways that activate or detoxify carcinogens, and exposure to lawns or gardens treated with phenoxy herbicides could potentially be associated with the increased risk of TCC in Scottish terriers.
Oncogenes are genes that when mutated, or expressed at high levels, cause normal cells to transition into cancer cells. The process is typically helped along by the effects of environmental carcinogens, viruses, and other stressors. In contradistinction to oncogenes, tumor suppressor genes, or antioncogenes as they are sometimes called, protect normal cells from transitioning into cancerous ones. A mutation in these genes can cause a loss of or reduction in this protective function.
3.3.8 Genetics and Behavior
Similar to cancer, little doubt exists that genetics plays a key role in predicting behaviors, and yet we are very early in the process of characterizing the process. Behaviors such as herding and retrieving are firmly entrenched in some breeds, and we are getting closer to understanding the genetic bases for these traits. In addition, it appears that dogs have evolved a social–cognitive specialization that allows them unusual skill in cooperating and communicating with humans [4]. In fact, dogs and humans accept each other into a mutual social structure, which appears to have been the result of genetic selection. Behavioral traits do have a genetic basis, and a high degree of genetic correlation between traits is often found.
Some developments have occurred in identifying quantitative trait loci (QTLs) important in some behavioral conditions, but much more is to be learned in years to come. Because behaviors are often conserved within breed groups, individual qualities (e.g., retrieving ability) can often be achieved by the appropriate selection of specific breeds, especially if representative family members can be observed. For mixed‐breed dogs, a rough approximation might be accomplished by discerning which breeds primarily contributed to an individual animal through commercially available genetic breed profiles.
Genes don't cause diseases, but they may code for defective proteins that are associated with disease states.
Most traits are considered dominant or recessive, but that classification is not absolute in most cases.
DNA testing can be used to identify risk, but may not be absolute in predictions of clinical disease due to the properties of penetrance and expressivity.
While some diseases may be caused by a defect attributed to variants in a single gene pair, the majority of diseases are caused by an interaction of multiple genes together with environmental factors.
Genetic diseases can be attributable to more than just variants in nuclear or mitochondrial DNA; the epigenome appears to also play a significant role in disease manifestations.
Abbreviation
DNA Deoxyribonucleic acid
References
1 1 Swanson, K.S. (2006). Nutrient–gene interactions and their role in complex diseases in dogs. J. Am. Vet. Med. Assoc. 228 (10): 1513–1520.
2 2 Giger, U., Sargan, D.R., and McNiel, E.A. (2006). Breed‐specific hereditary diseases and genetic screening. In: The Dog and its Genome (eds. E.A. Ostrander, U. Giger and K. Lindeblad‐Toh), 249–289. New York: Cold Spring Harbor Laboratory Press.
3 3 Knapp, D.W., Glickman, N.W., DeNicola, D.B. et al. (2000). Naturally‐occurring canine transitional cell carcinoma of the urinary bladder: a relevant model of human invasive bladder cancer. Urol. Oncol. 5: 47–59.
4 4 Hare, B. and Tomasello, M.
