Population genomic analysis provides evidence of the past success and future potential of South China tiger captive conservation.

BACKGROUND: Among six extant tiger subspecies, the South China tiger (Panthera tigris amoyensis) once was widely distributed but is now the rarest one and extinct in the wild. All living South China tigers are descendants of only two male and four female wild-caught tigers and they survive solely in zoos after 60 years of effective conservation efforts. Inbreeding depression and hybridization with other tiger subspecies were believed to have occurred within the small, captive South China tiger population. It is therefore urgently needed to examine the genomic landscape of existing genetic variation among the South China tigers. RESULTS: In this study, we assembled a high-quality chromosome-level genome using long-read sequences and re-sequenced 29 high-depth genomes of the South China tigers. By combining and comparing our data with the other 40 genomes of six tiger subspecies, we identified two significantly differentiated genomic lineages among the South China tigers, which harbored some rare genetic variants introgressed from other tiger subspecies and thus maintained a moderate genetic diversity. We noticed that the South China tiger had higher FROH values for longer runs of homozygosity (ROH > 1 Mb), an indication of recent inbreeding/founder events. We also observed that the South China tiger had the least frequent homozygous genotypes of both high- and moderate-impact deleterious mutations, and lower mutation loads than both Amur and Sumatran tigers. Altogether, our analyses indicated an effective genetic purging of deleterious mutations in homozygous states from the South China tiger, following its population contraction with a controlled increase in inbreeding based on its pedigree records. CONCLUSIONS: The identification of two unique founder/genomic lineages coupled with active genetic purging of deleterious mutations in homozygous states and the genomic resources generated in our study pave the way for a genomics-informed conservation, following the real-time monitoring and rational exchange of reproductive South China tigers among zoos.

[Simultaneous modulated accelerated radiation therapy in the treatment of nasopharyngeal cancer].

OBJECTIVE: To evaluate the toxicity and clinical efficacy of simultaneous modulated accelerated radiation therapy (SMART) technique for nasopharyngeal carcinoma. METHODS: 110 patients with nasopharyngeal carcinoma underwent boost treatment with SMART at the dose of 2.5 Gy/time for 28 times for gross tumor volume (GTV) with the total dose of 70 Gy and the dose of 2.0 Gy/time once a day and 5 times a week, totally 28 times, with the total dose of 56 Gy for the clinical treatment volume (CTV). The GTV dose for 36 of these patients was boosted to 80 Gy. Follow-up was conducted for 24 months (7 - 44 months). RESULTS: Follow-up showed that the 1, 2, and 3-year survival rates were 97.02%, 88.72%, and 78.27%, respectively. The 1 - 3 year local relapse-free survival rate was 97.94% (95.10% - 100%). The 1, 2, and 3-yea local-regional relapse-free rates and distant metastasis-free rates were 95.21%, 89.83%, 76.10% and 95.38%, 85.71%, and 79.67%, respectively. According to the Fuzhou staging, the 3-year overall survival rate of the stage I - II patients was 100%, while the 3-year survival rate of the stage III patients was 74.33% and the 3-year survival rate of stage IV a patients was 62.96%. The acute toxicity was well tolerated except for the high incidence of severe mucositis. No grade 4 side effects occurred. Most of the patients showed Grade 0 to 1 late toxicity and xerostomia was a common side effect. No increase of toxicity was seen when the GTV dose was increased to 80 Gy. CONCLUSION: SMART yields superior dose distribution over the traditional radiotherapy in nasopharyngeal carcinoma at the early or advanced stages. The local-regional control was excellent and distant metastasis remains the main risk. Dose escalation to 80 Gy was safe and feasible. Toxicity of SMART is acceptable and tolerable.