Rare Disease Genes—Lessons and Challenges
- Department of Human Molecular Genetics, National Public Health Institute and Institute of Biomedicine, University of Helsinki, FIN-00300 Helsinki, Finland
This extract was created in the absence of an abstract.
The fiercest competition in the field of human genetics takes place in the area of genetic diseases that are common at the population level—this is primarily attributable to the potential commercial utilization of emerging data. However, dissection of the molecular background of many extremely rare diseases has proven to be highly useful for the detailed characterization of cellular dysfunction and the identification of novel metabolic pathways, broadening our understanding of biological processes in general. This information has largely been obtained from research carried out in populations with exceptional enrichment of a given disease (Fig. 1).
The identification of a disease mutation is considered beneficial, as it provides tools for assessing the pathogenic mechanisms of the disease and ultimately designing prevention and therapy. Research into the molecular background of many rare disorders has also provided the scientific community with various new strategies for the locus identification of a disease gene, as well as given new insight into metabolic pathways and biological processes.
Although the global prevalence of rare diseases is insignificant [e.g., worldwide there are <200 known cases of patients with infantile-type neuronal ceroid lipofuscinosis (INCL) in comparison to a global population prevalence of 1:65 for the recessive cystic fibrosis mutation or 1:8000 for dominant Marfan syndrome], this rarity does not necessarily reflect the impact of these diseases on biological research.
From Population Sample to Gene Identification: Special Statistical Strategies
Rare diseases are characteristically enriched in populations that have been isolated for religious, linguistic or geographical reasons; good examples of this are the Ashkenazi Jews or the Finns. From the viewpoint of population genetics, rare diseases have initially led to the identification of many population bottlenecks and have produced quite precise data on the time period at which the mutation was actually introduced into the population, thus providing initial clues …
