GENETICS IN PARKINSON DISEASE
A round of sequencing takes several hours to prepare.
Although Parkinson disease was once considered a sporadic disease, there are genetic components of Parkinson’s disease that now provide the foundation for neuroscience research. The identification of genetic mutations in patients with Parkinson disease has major significance. Each discovery gives novel direction to the field and renews hope for therapies to treat motor and non-motor features, to alleviate symptoms and slow disease progression.
In order to identify additional genetic determinants of disease, at the Centre for Applied Neurogenetics (CAN), we are working together with an international network of neurologists and researchers to characterize the “Parkinson’s Genome”, focusing on pedigree-based (family) genetics and population genetics.
FAMILY GENETICS
Approximately 15% of people with Parkinson’s disease have a family history of the condition, in other words, one or more of their relatives are also affected. In multi-incident families, those with two or more affected family members, Parkinson’s disease appears more commonly than in the general population. This higher frequency of disease may be due to a shared genetic susceptibility among blood-relatives. In these families we are now applying the latest technologies in human genetics to find that specific gene(s) responsible for Parkinson’s disease.
Figure 1 is a representative pedigree of a multi-incident family. The circles indicate females; the squares indicate males. Filled symbols represent family members who have been diagnosed with Parkinson’s disease, while non-filled shapes indicate healthy individuals. In this particular example, we have a three generation family in which six family members have been diagnosed with disease. The Parkinson’s susceptibility gene was passed from the grandparent (square in the top left) to two of his three children, and those in turn passed it onto three of the grandchildren.
The work we are doing cannot be successful without the help of families in which two or more persons are affected by Parkinson’s disease (or a related neurodegenerative disorder). For families interested in being involved in research, we ask for some clinical information on diagnoses and a small blood sample (2 teaspoons) for genetic analysis. All data are de-identified to ensure participant confidentiality.
Contact with patients and family members begins via referral by a movement disorder specialist, neurologist, or family physician. For more information, please contact us at: 
In order to maximize the number of samples we are able to analyze per day, our lab is equipped with robotics to enhance the throughput at various stages of sequencing.
We start by interviewing the contact person (the proband) in the family. However, to identify the genetic causes of disease, we also need to interview and receive blood samples from as many family members as possible; especially, but not exclusively, those who have also been diagnosed with disease. We will ask the proband to let other family members know about our study and, if they wish to participate, we ask them to contact us. Our aim is for everyone to feel comfortable and participate enthusiastically. No one should feel obligated or pressured to participate in a study. The laboratory work generally takes several years of effort and expense and mutual trust is important. Over the years, we have developed a good working relationship with hundreds of physicians and families throughout Canada, the U.S. and across the globe.
Once we receive blood samples from all participating family members, we use these samples to extract DNA. This DNA is then screened for the presence of genetic changes implicated in parkinsonism and other movement disorders. If none are found, and enough family members are available for further analysis, we will perform all the possible steps to determine the novel susceptible gene in the family.
Genetic research discoveries are driving novel pharmaceutical development but it takes time and investment. As yet no specific medications have been made for gene mutation carriers in Parkinson’s disease, and new treatments can be offered based on this knowledge. Nonetheless, should we discover a genetic predisposition to Parkinson’s disease in your DNA sample, and within your family, you have the right to be informed. In rare instances, we send research participants a letter that details the scientific advance that is relevant to you and your family. If desired, via discussion with your family physician or neurologist, you may request more specific, individual genetic counselling and genetic testing. For some genes and mutations this testing is commercially available.
The success of our research hinges on acquiring enough samples from families with multiple people diagnosed with Parkinson’s disease or a related form of neurodegeneration such as forms of Parkinsonism, Progressive Supranuclear Palsy , Corticobasal Ganglionic Degeneration CBD, and Dementia with Lewy Bodies. For more infomation please contact us at:
There is no profit or financial gain to the researchers from this work. Academic clinicians and scientists are driven by the need to find the genetic causes for Parkinson’s disease in order to develop better treatments. All research findings are de-identified to ensure participant confidentiality. The risk of taking part is minimal but the contribution of these discoveries to patients with Parkinson’s disease and to society may be immense.
POPULATION GENETICS
Population genetics has been used to identify association with disease susceptibility genes. In contrast to family studies, population genetics rely on a large number of patients (unrelated) and healthy individuals. Multiple regions of the genome (loci) are implicated by these studies, with common DNA variability (polymorphisms), rather than one specific gene or mutation.
We sequence DNA obtained from patients to find new mutations.
Most cases of Parkinson’s disease are the result of a complex mix of several genetic changes and environmental factors. However, as biological organisms, our genetic makeup helps determine the likelihood of developing a specific disease, and how well we are able to fight its progression. Our genetic makeup also plays a role in how well we handle the side effects of medications, such as Levodopa.
Finding susceptibility genes within a population is equally challenging as finding a genetic susceptibiity within a family. Frequently these genetic risk factors in susceptibility genes have only a small effect; and independently are not sufficient to cause disease. However, small contributions by several of these risk genes in combination with specific environmental factors may lead to Parkinson’s disease.
Only when enough patients with Parkinson’s disease and healthy individuals are willing to participate, we can identify these susceptibility factors. We are presently involved in population genetic studies in Canada, Tunisia, France, Chile, India, Norway, Taiwan, Korea, Japan, Nigeria, Ireland, UK, Italy, Germany and the United States. However, the larger the sample size, the more efficient and accurate are the research findings.
For most people with Parkinson’s, the disease appears sporadic as nobody else in the family is affected. However, we can still learn a lot about genetic susceptibility if you (and potentially your spouse and/or unaffected sibling) will consider taking part in a research study.
MOLECULAR GENETICS
Over the years, several genes causing familial Parkinson’s disease, as well as susceptibility genes, have been identified. However, identifying the genetic determinants of disease in these patients is only the beginning of the process. We use a variety of approaches to translate the information gained from these genetic discoveries into useful therapies for patients. One set of approaches is to develop biological models of the disease that will allow us to test predictions about how damaging genes produce specific symptoms, and to use these to develop new therapies. More specifically, we might use cells in culture in the laboratory to try and understand the details of how cells are affected, and how we may reverse these changes.
Thermocyclers for PCR reactions, which amplify DNA extracted from patient blood to give us sufficient amounts of DNA to work with during experiments.
What does genetics tell us? Genes are sequences of DNA which are passed on from parents to children, with each parent contributing half of their genes to the child. These changes are generally passed on from one generation to the next. This pattern of inheritance can be used to predict the likelihood that members of a family are going to be affected.
What genetics does not tell us directly is how the DNA sequence in those genes manifests itself as a series of symptoms that we recognize as a disease. The gap between gene identification and development of better models and more efficacious treatments is due to gaps in our understanding of how the machinery of our bodies actually works in molecular detail. The work we are doing at CAN takes advantage of genetics findings from family and population genetics to fill these gaps in our knowledge.
Greater insight into the genetic and functional aspects of Parkinson disease and associated neurodegeneration will improve diagnosis and allow better treatments to be developed to ultimately affect a cure. If you would like to learn more about our research, please contact us at about@can.ubc.ca.
For more information on how you can directly contribute to research please contact: 
