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Genetic diversity estimates for the Caenorhabditis Intervention Testing Program screening panel.

ABSTRACT: The Caenorhabditis Intervention Testing Program (CITP) was founded on the principle that compounds with positive effects across a genetically diverse test-set should have an increased probability of engaging conserved biochemical pathways with mammalian translational potential. To fulfill its mandate, the CITP uses a genetic diversity panel of Caenorhabditis strains for assaying longevity effects of candidate compounds. The panel comprises 22 strains from three different species, collected globally, to achieve inter-population genetic diversity. The three represented species, C. elegans, C. briggsae, and C. tropicalis, are all sequential hermaphrodites, which simplifies experimental procedures while maximizing intra-population homogeneity. Here, we present estimates of the genetic diversity encapsulated by the constituent strains in the panel based on their most recently published and publicly available whole-genome sequences, as well as two newly generated genomic data sets. We observed average genome-wide nucleotide diversity (π) within the C. elegans (1.2e-3), C. briggsae (7.5e-3), and C. tropicalis strains (2.6e-3) greater than estimates for human populations, and comparable to that found in mouse populations. Our analysis supports the assumption that the CITP screening panel encompasses broad genetic diversity, suggesting that lifespan-extending chemicals with efficacy across the panel should be enriched for interventions that function on conserved processes that are shared across genetic backgrounds. While the diversity panel was established by the CITP for studying longevity interventions, the panel may prove useful for the broader research community when seeking broadly efficacious interventions for any phenotype with potential genetic background effects.

SUBMITTER: Teterina AA

PROVIDER: S-EPMC8796004 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveThere can be extreme variability between individual responses to exercise training, and the identification of genetic variants associated with individual variabilities in exercise-related traits could guide individualized exercise programs. We aimed to screen the exercise-related gene sensitivity of patients with acute myocardial infarction after PCI by establishing the gene spectrum of aerobic exercise and cardiopulmonary function sensitivity, test the effect of individualized precision exercise therapy, and provide evidence for the establishment of a precision medicine program for clinical research.MethodsAerobic exercise- and cardiopulmonary function-related genes and single-nucleotide polymorphisms (SNPs) were obtained by data mining utilizing a major publicly available biomedical repository, the NCBI PubMed database. Biological samples from all participants underwent DNA testing. We performed SNP detection using Samtools. A total of 122 patients who underwent PCI were enrolled in the study. We screened the first 24 cases with a high mutation frequency for aerobic exercise- and cardiopulmonary function-related genes and the last 24 cases with a low mutation frequency and separated them into two groups for the exercise intervention experiment.ResultsIn both the low mutation frequency group and the high mutation frequency group, after 8 weeks of exercise intervention, 6 MWT distance, 6 MWT%, VO2/kg at peak, and VO2/kg at AT were significantly improved, and the effect in the high mutation frequency group was significantly higher than that in the low mutation frequency group (6 MWT distance: 468 vs. 439, P=0.003; 6 MWT%: 85 vs. 77, P=0.002, VO2/kg at peak: 14.7 vs. 13.3, P=0.002; VO2/kg at AT: 11.9 vs. 13.3, P=0.003).ConclusionsThere is extreme variability between individual responses to exercise training. The identification of genetic variants associated with individual variabilities in exercise-related traits could guide individualized exercise programs. We found that the subjects with a high mutation frequency in aerobic exercise and cardiopulmonary function-related genes achieved more cardiorespiratory fitness benefits in the aerobic exercise rehabilitation program and provided evidence for the establishment of a precision medicine program for clinical research.

Project description:Flooding is a devastating abiotic stress that endangers crop production in the twenty-first century. Because of the severe susceptibility of common bean (Phaseolus vulgaris L.) to flooding, an understanding of the genetic architecture and physiological responses of this crop will set the stage for further improvement. However, challenging phenotyping methods hinder a large-scale genetic study of flooding tolerance in common bean and other economically important crops. A greenhouse phenotyping protocol was developed to evaluate the flooding conditions at early stages. The Middle-American diversity panel (n = 272) of common bean was developed to capture most of the diversity exits in North American germplasm. This panel was evaluated for seven traits under both flooded and non-flooded conditions at two early developmental stages. A subset of contrasting genotypes was further evaluated in the field to assess the relationship between greenhouse and field data under flooding condition. A genome-wide association study using ~150 K SNPs was performed to discover genomic regions associated with multiple physiological responses. The results indicate a significant strong correlation (r > 0.77) between greenhouse and field data, highlighting the reliability of greenhouse phenotyping method. Black and small red beans were the least affected by excess water at germination stage. At the seedling stage, pinto and great northern genotypes were the most tolerant. Root weight reduction due to flooding was greatest in pink and small red cultivars. Flooding reduced the chlorophyll content to the greatest extent in the navy bean cultivars compared with other market classes. Races of Durango/Jalisco and Mesoamerica were separated by both genotypic and phenotypic data indicating the potential effect of eco-geographical variations. Furthermore, several loci were identified that potentially represent the antagonistic pleiotropy. The GWAS analysis revealed peaks at Pv08/1.6 Mb and Pv02/41 Mb that are associated with root weight and germination rate, respectively. These regions are syntenic with two QTL reported in soybean (Glycine max L.) that contribute to flooding tolerance, suggesting a conserved evolutionary pathway involved in flooding tolerance for these related legumes.

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Genetic diversity estimates for the Caenorhabditis Intervention Testing Program screening panel.

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