Provision of a molecularly confirmed diagnosis in a timely manner for children and adults with rare genetic diseases shortens their "diagnostic odyssey," improves disease management, and fosters genetic counseling with respect to recurrence risks while assuring reproductive choices. In a general clinical genetics setting, the current diagnostic rate is approximately 50%, but for those who do not receive a molecular diagnosis after the initial genetics evaluation, that rate is much lower. Diagnostic success for these more challenging affected individuals depends to a large extent on progress in the discovery of genes associated with, and mechanisms underlying, rare diseases. Thus, continued research is required for moving toward a more complete catalog of disease-related genes and variants. The International Rare Diseases Research Consortium (IRDiRC) was established in 2011 to bring together researchers and organizations invested in rare disease research to develop a means of achieving molecular diagnosis for all rare diseases. Here, we review the current and future bottlenecks to gene discovery and suggest strategies for enabling progress in this regard. Each successful discovery will define potential diagnostic, preventive, and therapeutic opportunities for the corresponding rare disease, enabling precision medicine for this patient population.
- MeSH
- databáze faktografické MeSH
- exom MeSH
- genom lidský MeSH
- lidé MeSH
- mezinárodní spolupráce * MeSH
- vzácné nemoci diagnóza genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Marine organisms adapt to complex temporal environments that include daily, tidal, semi-lunar, lunar and seasonal cycles. However, our understanding of marine biological rhythms and their underlying molecular basis is mainly confined to a few model organisms in rather simplistic laboratory settings. Here, we use new empirical data and recent examples of marine biorhythms to highlight how field ecologists and laboratory chronobiologists can complement each other's efforts. First, with continuous tracking of intertidal shorebirds in the field, we reveal individual differences in tidal and circadian foraging rhythms. Second, we demonstrate that shorebird species that spend 8-10 months in tidal environments rarely maintain such tidal or circadian rhythms during breeding, likely because of other, more pertinent, temporally structured, local ecological pressures such as predation or social environment. Finally, we use examples of initial findings from invertebrates (arthropods and polychaete worms) that are being developed as model species to study the molecular bases of lunar-related rhythms. These examples indicate that canonical circadian clock genes (i.e. the homologous clock genes identified in many higher organisms) may not be involved in lunar/tidal phenotypes. Together, our results and the examples we describe emphasize that linking field and laboratory studies is likely to generate a better ecological appreciation of lunar-related rhythms in the wild.This article is part of the themed issue 'Wild clocks: integrating chronobiology and ecology to understand timekeeping in free-living animals'.
- MeSH
- Charadriiformes fyziologie MeSH
- cirkadiánní hodiny * MeSH
- cirkadiánní rytmus * MeSH
- cizopasní červi fyziologie MeSH
- členovci fyziologie MeSH
- vodní organismy fyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
