Related Experiment Video
Updated: May 16, 2026
Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Genetics 101 for cardiologists: rare genetic variants and monogenic cardiovascular disease
Sali M K Farhan1, Robert A Hegele
1Departments of Medicine and Biochemistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
Insights
Mapping monogenic diseases
Area of Science:
- Genetics
- Molecular Biology
- Medical Genetics
Background:
- Monogenic diseases, caused by single gene mutations, follow Mendelian inheritance patterns.
- Over 7000 monogenic diseases exist, collectively causing up to 10% of clinical illnesses.
- Individual conditions are rare, but their genetic basis is crucial for understanding disease.
Purpose of the Study:
- To highlight the importance of identifying causative genes and mutations in monogenic diseases.
- To emphasize the role of genetic discoveries in enabling early diagnosis and genetic counseling.
- To underscore how studying rare genetic disorders can reveal fundamental biological pathways and inform broader therapeutic strategies.
Main Methods:
- Review of existing literature and databases on monogenic diseases.
- Analysis of inheritance patterns (dominant, recessive, X-linked).
- Case examples illustrating the link between genetic mutations and clinical phenotypes.
Main Results:
- Identification of causative genes and mutations provides actionable information for genetic counseling and early diagnosis.
- Understanding gene function in monogenic diseases offers insights into cellular and biochemical pathways.
- Research into rare genetic conditions, like familial hypercholesterolemia, has led to significant therapeutic advancements, such as statins.
Conclusions:
- Mapping monogenic diseases is vital for genetic counseling, early diagnosis, and intervention.
- Discovering gene-phenotype correlations advances our understanding of molecular pathways.
- Studying rare genetic disorders can pave the way for novel treatments applicable to both rare and common diseases.
Abstract:
Monogenic diseases have a distinctive familial inheritance that follows Mendel's laws, showing patterns like dominant, recessive, or X-linked. There are > 7000 monogenic diseases curated in databases, and together they account for up to 10% of all illnesses encountered in the emergency room or clinic. Despite the rarity of individual monogenic conditions, mapping their causative genes and mutations is important for several reasons. First, knowing the causative gene and mutation could provide actionable information for genetic counselling. Sometimes, knowing the gene and mutation allows for early diagnosis in affected families, which is important if there is an evidence-based intervention. Second, the implication of a mutant gene as being causative for a clinical phenotype provides strong evidence of the importance of the gene product in a cellular or biochemical pathway. Discovery of new molecular pathways in families with rare diseases can serve as the first step toward developing rational therapies to help not only affected families, but also patients with less extreme, nongenetic forms of the same condition. For instance, the study of rare patients with familial hypercholesterolemia helped in developing statin drugs, initially as a treatment for familial hypercholesterolemia but now a widely used therapy to reduce low-density lipoprotein cholesterol and cardiovascular disease risk.
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