Gene Imprinting of the X Chromosome may Affect Progression in MS

Start Term
End Term
Funding Amount
$50,000
Affiliation(s)
Laval University
Geographic Region(s) / Province(s)
Quebec
Researcher(s)
Dr. Manu Rangachari
Research Priorities
Progressive MS
Impact Goal(s)
Understand and Halt Disease Progression

Summary:

  • The manner in which our genes are expressed (i.e. turned on or off) in the different cells of our body can be inherited from our parents, a process known as ‘gene imprinting’. 
  • Dr. Manu Rangachari and team have found that genetically identical female mice can have very different disease outcomes. They believe this is a result of a gene imprinting effect in the X chromosome that is passed down specifically from the father to the daughters. In this study, the researchers will identify which X chromosome genes from the father are likely to impact disease outcomes in the daughter mice. 
  • This research has the potential to uncover new genes associated with multiple sclerosis (MS) disease severity and progression, allowing clinicians to better predict the likelihood of someone developing progressive disease to inform treatment decisions.

Project Description: 
Predicting disease outcomes in people with MS is a current challenge. There is evidence suggesting a role for ‘epigenetics’– where the environment or behaviour can influence the way genes are expressed (turn on or off) – in determining progressive disease outcomes in MS. Epigenetic changes can also be inherited from parents to children in a process called ‘gene imprinting’.

Dr. Manu Rangachari and team will determine if gene imprinting can influence disease outcomes in mice with MS-like disease. They have found from previous studies that genetically identical female mice can have different progressive disease outcomes – some female mice develop very severe progressive MS-like disease whereas others show a more modest, non-progressive disease. These differences are likely due to a gene imprinting effect in the X chromosome that is passed down specifically from the father to the daughters. In this study, the researchers will identify which X chromosome genes from the father are likely to impact disease outcomes in the daughter mice. The clinical relevance of these genes will be validated using human genetics data from the CanProCo study.

Potential Impact: The findings of this study may uncover new genes that are associated with MS disease severity and progression. This knowledge will allow clinicians to better predict the likelihood of someone with MS to develop progressive disease and make informed treatment decisions.

Project Status: In Progress