The impact of clinical genome sequencing in a global population with suspected rare genetic disease.

There is mounting evidence of the value of clinical genome sequencing (cGS) in individuals with suspected rare genetic disease (RGD), but cGS performance and impact on clinical care in a diverse population drawn from both high-income countries (HICs) and low- and middle-income countries (LMICs) has not been investigated. The iHope program, a philanthropic cGS initiative, established a network of 24 clinical sites in eight countries through which it provided cGS to individuals with signs or symptoms of an RGD and constrained access to molecular testing. A total of 1,004 individuals (median age, 6.5 years; 53.5% male) with diverse ancestral backgrounds (51.8% non-majority European) were assessed from June 2016 to September 2021. The diagnostic yield of cGS was 41.4% (416/1,004), with individuals from LMIC sites 1.7 times more likely to receive a positive test result compared to HIC sites (LMIC 56.5% [195/345] vs. HIC 33.5% [221/659], OR 2.6, 95% CI 1.9-3.4, p < 0.0001). A change in diagnostic evaluation occurred in 76.9% (514/668) of individuals. Change of management, inclusive of specialty referrals, imaging and testing, therapeutic interventions, and palliative care, was reported in 41.4% (285/694) of individuals, which increased to 69.2% (480/694) when genetic counseling and avoidance of additional testing were also included. Individuals from LMIC sites were as likely as their HIC counterparts to experience a change in diagnostic evaluation (OR 6.1, 95% CI 1.1-∞, p = 0.05) and change of management (OR 0.9, 95% CI 0.5-1.3, p = 0.49). Increased access to genomic testing may support diagnostic equity and the reduction of global health care disparities.

When resilience is not enough: 2022 extreme marine heatwave threatens climatic refugia for a habitat-forming Mediterranean octocoral.

Climate change is impacting ecosystems worldwide, and the Mediterranean Sea is no exception. Extreme climatic events, such as marine heat waves (MHWs), are increasing in frequency, extent and intensity during the last decades, which has been associated with an increase in mass mortality events for multiple species. Coralligenous assemblages, where the octocoral Paramuricea clavata lives, are strongly affected by MHWs. The Medes Islands Marine Reserve (NW Mediterranean) was considered a climate refugia for P. clavata, as their populations were showing some resilience to these changing conditions. In this study, we assessed the impacts of the MHWs that occurred between 2016 and 2022 in seven shallow populations of the octocoral P. clavata from a Mediterranean Marine Protected Area. The years that the mortality rates increased significantly were associated with the ones with strong MHWs, 2022 being the one with higher mortalities. In 2022, with 50 MHW days, the proportion of total affected colonies was almost 70%, with a proportion of the injured surface of almost 40%, reaching levels never attained in our study site since the monitoring was started. We also found spatial variability between the monitored populations. Whereas few of them showed low levels of mortality, others lost around 75% of their biomass. The significant impacts documented here raise concerns about the future of shallow P. clavata populations across the Mediterranean, suggesting that the resilience of this species may not be maintained to sustain these populations face the ongoing warming trends.

El canvi climatic està impactant els ecosistemes arreu del planeta, i el Mar Mediterrani no n'és una excepció. Els esdeveniments climàtics extrems, com ara les onades de calor marines, estan augmentant en freqüència, extensió i intensitat en les darreres dècades, i estan sent associades a un increment dels esdeveniments de mortalitat massiva de múltiples espècies. El coral·ligen, on hi viu l'octocorall Paramuricea clavata, està altament afectat per les onades de calor marines. La Reserva Marina de les Illes Medes (NO del Mediterrani) es considerava un refugi climàtic per aquesta espècie, degut a que les seves poblacions mostraven certa resiliència a les condicions canviants. En aquest estudi hem avaluat els impactes de les onades de calor marines succeïdes entre els anys 2016 i 2022 a set poblacions someres de l'octocorall P. clavata, en una Àrea Marina Protegida del Mediterrani. Els anys en els quals les taxes de mortalitat van incrementar significativament s'associen amb els anys amb fortes onades de calor marines, sent el 2022 l'any amb la mortalitat més elevada. Al 2022, amb 50 dies d'onada de calor, la proporció total de colònies afectades va ser prop del 70%, amb un percentatge de superfície afectada de gairebé el 40%, arribant a valors mai observats en el lloc d'estudi des de que es va iniciar el seguiment d'aquestes poblacions. També hem observat variabilitat espacial entre les poblacions mostrejades. Mentre que algunes d'elles han mostrat poca mortalitat, altres han perdut al voltant del 75% de la seva biomassa. Els impactes documentats en aquest estudi mostren un futur preocupant de les poblacions someres de P. clavata arreu del Mediterrani, i això suggereix que la resiliència d'aquesta espècie podria no ser suficient per mantenir les seves poblacions en l'escenari d'escalfament que es preveu.