Conectar
by Claude Emmanuel Koutouan, Marie Louisa Ramaroson, Angelina El Ghaziri, Laurent Ogé, Abdelhamid Kebieche, Raymonde Baltenweck, Patricia Claudel, Philippe Hugueney, Anita Suel, Sébastien Huet, Linda Voisine, Mathilde Briard, Jean Jacques Helesbeux, Latifa Hamama, Valérie Le Clerc, Emmanuel Geoffriau
Resistance of carrot to Alternaria leaf blight (ALB) caused by Alternaria dauci is a complex and quantitative trait. Numerous QTL for resistance (rQTLs) to ALB have been identified but the underlying mechanisms remain largely unknown. Some rQTLs have been recently proposed to be linked to the flavonoid content of carrot leaves. In this study, we performed a metabolic QTL analysis and shed light on the potential mechanisms underlying the most significant rQTL, located on carrot chromosome 6 and accounting for a large proportion of the resistance variation. The flavonoids apigenin 7-O-rutinoside, chrysoeriol 7-O-rutinoside and luteolin 7-O-rutinoside were identified as strongly correlated with resistance. The combination of genetic, metabolomic and transcriptomic approaches led to the identification of a gene encoding a bHLH162-like transcription factor, which may be responsible for the accumulation of these rutinosylated flavonoids. Transgenic expression of this bHLH transcription factor led to an over-accumulation of flavonoids in carrot calli, together with significant increase in the antifungal properties of the corresponding calli extracts. Altogether, the bHLH162-like transcription factor identified in this work is a strong candidate for explaining the flavonoid-based resistance to ALB in carrot.by Wenshu Li, Jeffrey A. Leibowitz, Shuoguo Wang, Louisa Walker, Chang Xu, Kuei-Ting Chen, Alexa B. Schrock, Jason Hughes, Nimesh Patel, Julia A. Elvin, Lauren L. Ritterhouse, Ethan Sokol, Garrett Frampton, Lucas Dennis, Bahar Yilmazel, Brennan Decker
Homologous recombination repair (HRR) is a cellular pathway for high-fidelity double strand DNA break repair that uses the sister chromatid as a guide to ensure chromosomal integrity and cell viability. Deficiency in the HRR pathway (HRD) can sensitize tumors to poly (ADP-ribose) polymerase inhibitors (PARPi) and platinum-based chemotherapy, offering an avenue to identify patients who may benefit from targeted therapies. HRD signature (HRDsig) is a pan-solid-tumor biomarker on the FoundationOne®CDx (F1CDx®) assay that employs a DNA scar-based approach to calculate a score based on copy number features (e.g., segment size, oscillation patterns, and breakpoints per chromosome arm) and does not rely on HRR gene alterations, enabling detection of genomic and epigenetic mechanisms of HRD. After finalizing the HRDsig algorithm, analytical validation was conducted in a CAP-accredited, CLIA-certified laboratory on 278 solid tumor and normal tissue specimens. HRDsig results were compared with an independent HRD biomarker, defined by the presence of a reversion mutation restoring HRR gene function. In this evaluation, 100 HRD-positive and 126 HRD-negative samples showed a positive percent agreement of 90.00% and a negative percent agreement of 94.44%. The limit of detection (LoD) was estimated at 23.04% tumor purity, with the limit of blank (LoB) confirmed as zero in 60 normal tissue replicates. Reproducibility testing on 11 positive and 11 negative samples across multiple labs, reagent lots, and sequencers yielded agreement in 99.49% of positive and 99.73% of negative replicates. HRDsig status remained consistent in the presence of interfering substances, demonstrating 100% concordance in spiked samples. These validation results underscore the high analytical concordance, low false-positive rate, and overall robustness of HRDsig for reliable assessment of homologous recombination deficiency.
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