OMIM and Rare Diseases: Unraveling the Genetic Mysteries
The quest to understand and combat rare diseases has long been a complex challenge within the medical and scientific community. At the heart of this challenge lies the Online Mendelian Inheritance in Man (OMIM) database, a critical resource for geneticists and researchers dedicated to unraveling the mysteries of rare genetic disorders. This blog post delves into the intricacies of OMIM and its pivotal role in advancing our understanding of rare diseases, drawing on the latest scientific research to illuminate the path forward.
Understanding OMIM: A Beacon in Rare Disease Research
OMIM, a comprehensive, freely accessible database, catalogs human genes and genetic phenotypes, focusing on the genetic relationship between diseases and inherited conditions. Its detailed entries provide insights into the molecular basis of diseases, offering a foundation for research into diagnostics, treatment, and prevention strategies for rare diseases.
Recent analyses have highlighted the significant challenges and opportunities within the realm of rare disease research. Hartley et al. (2018) underscored the complexity of estimating the total number of rare genetic diseases, traditionally pegged at between 6,000 and 8,000. Their examination of OMIM entries without confirmed molecular etiologies reveals that many unsolved phenotypic entries likely represent pathogenic variants in known genes, suggesting the potential for novel gene discovery is vast, yet underexplored.
The Rare Disease Atlas: A Complex Landscape
The quest to map the "rare disease atlas" is fraught with challenges. Boycott (2016) posited that, while the rapid advancements in next-generation sequencing (NGS) have accelerated disease-gene association discoveries, a significant portion of rare diseases remains elusive. The prediction that most remaining disease genes would be identified by 2020 now seems optimistic, as the field moves toward a more nuanced understanding of rare disease genomics and the intricacies of phenotypic heterogeneity.
Challenges and Opportunities in Therapy Development
The development of therapies for rare diseases remains a daunting challenge. Chen and Altman (2017) explored the landscape of orphan medicinal products (OMPs), finding that diseases with gain-of-function mutations or those amenable to allostery present promising avenues for drug development. Their analysis suggests a targeted approach could potentially bridge the gap between genetic discovery and therapeutic application, underscoring the need for continued innovation and collaboration within the research community.
Refenrece:
Hartley, T., Balcı, T. B., Rojas, S. K., Eaton, A., Canada, C., Dyment, D. A., & Boycott, K. M. (2018, December). The unsolved rare genetic disease atlas? An analysis of the unexplained phenotypic descriptions in OMIM®. In American Journal of Medical Genetics Part C: Seminars in Medical Genetics (Vol. 178, No. 4, pp. 458-463). Hoboken, USA: John Wiley & Sons, Inc..
Boycott, K. (2016). Depth of the rare genetic diseases: Strategies to identify the remaining genes and diseases.. Pathology, 48 Suppl 1, S30.
Chen, B., & Altman, R. (2017). Opportunities for developing therapies for rare genetic diseases: focus on gain-of-function and allostery. Orphanet Journal of Rare Diseases, 12.
