Question

In the movie, “A Dog’s Purpose”, Tino the corgi complains that going downstairs is hard because of his short legs. Short-legged dog breeds all carry a mutation that increases the amount of a growth factor with a role in bone development.

a. This is due to the gene dosage effect. What is the gene dosage effect and how does it cause increased levels of the growth factor? (1 mark)

b. Suggest one other mutation that would also cause more growth factor to be produced. Explain how your chosen mutation affects gene expression. (2 marks)

c. Cancer is the leading cause of death in dogs. Large breeds (like German Shepherd or St. Bernhard) are more likely to develop bone cancer. Is there a common gene that is affected in most of these animals? What is the normal role of the gene and explain how this gene is regulated? (3 marks)

d. The "Canberra Times" reports on a novel bone cancer treatment in dogs using gene therapy. The article described this therapy, in which a mutated molecule (referred to as the "guardian of the genome") will be outcompeted by the expression of a hundred times more of the wild-type gene. The introduced wild-type gene will be expressed in all cells. In your expert opinion will this therapy have an effect on the bone cancer? Will there be any side effects? Justify your answers. (3 marks)

e. Describe one factor that will affect the level of expression of the introduced gene. (1 mark)

Answer 1

A)

There appears to be a loose dichotomy between regulatory genes and their targets in that the former typically show a dosage effect on the phenotype, while the latter do not. This would imply that when new mutations arise in a heterozygote, adaptive evolution is the major mode of evolution on regulatory processes and neutral evolution is the primary mode on the target genes.

B)

Comprehensive studies of gene expression also provide an additional layer of information that is useful for predicting gene function. information about a gene's function can be deduced by identifying genes that share its expression pattern. Using a technique called cluster analysis, one can identify sets of genes that are coordinately regulated. Genes that are turned on or turned off together under a variety of different circumstances may work in concert in the cell: they may encode proteins that are part of the same multiprotein machine, or proteins that are involved in a complex coordinated activity, such as DNA replication or RNA splicing. Characterizing an unknown gene's function by grouping it with known genes that share its transcriptional behavior is sometimes called “guilt by association.” Cluster analyses have been used to analyze the gene expression profiles that underlie many interesting biological processes, including wound healing in humans

C)

As is the case in the human population, many different types of naturally occurring cancer may affect dogs and canine malignancies have been established as strong comparative models for the human disease due to their spontaneous development and frequency; dogs live in our environment and eat similar food and are thus exposed to similar risk factors, so the aetiology and pathogenesis of canine tumours is likely to be similar to that of human tumours [4–8]. A general comparison of the incidence of canine cancer with that of human cancer highlights some striking similarities and differences [9]. Breast cancer is the most common malignancy in women and the mammary gland is a common site for tumour development in bitches, although the risk is reduced in bitches spayed at a young age [10], demonstrating the importance of endogenous hormones in the development of this disease. In contrast, carcinomas of the prostate, a very common condition in men and also associated with hormonal stimulation, is relatively uncommon in dogs and occurs more frequently in neutered dogs [11]. Carcinomas of the lung and large bowel, the most common human tumours excluding breast and prostate, do not feature highly in the canine population, whereas soft tissue sarcomas, which are rare in humans, are relatively common in dogs.