Gene networks in hexaploid wheat: interacting quantitative trait loci for grain protein content

Abstract Background A major impediment in the treatment of ovarian cancer is the relapse of platinum-resistant tumors, which occurs in approximately 25% of patients. A better understanding of the biological mechanisms underlying platinum-based response will improve treatment efficacy through genetic testing and novel therapies.Methods Using data from high-grade serous ovarian carcinoma (HGSOC) patients in the Cancer Genome Atlas (TCGA), we classified those who remained progression-free for 12 months following platinum-based chemotherapy as “chemo-sensitive” (N=160) and those who had recurrence within six months as “chemo-resistant” (N=110). Univariate and multivariate analysis of expression microarrays identified differentially expressed genes and co-expression gene networks associated with chemotherapy response. Moreover, we integrated genomics data to determine expression quantitative trait loci (eQTL).Results Differential expression of the Valosin-containing protein (VCP) gene and five co-expression gene networks were associated with chemotherapy response in HGSOC. VCP and the gene networks contribute to protein processing in the endoplasmic reticulum, which has been implicated in chemotherapy response. These findings were successfully replicated using independent replication cohort. Furthermore, 192 QTLs were associated with these gene networks and BRCA2 expression.Conclusion This study implicates both known and novel genes as well as biological networks underlying response to platinum-based chemotherapy among HGSOC patients.

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Gene networks and expression quantitative trait loci associated with platinum-based chemotherapy response in high-grade serous ovarian cancer

10.1101/740696 ◽

2019 ◽

Cited By ~ 1

Author(s):

Jihoon Choi ◽

Anastasiya Tarnouskaya ◽

Sean Nesdoly ◽

Danai G. Topouza ◽

Madhuri Koti ◽

...

Keyword(s):

Ovarian Cancer ◽

Quantitative Trait Loci ◽

Quantitative Trait ◽

Gene Networks ◽

The Cancer Genome Atlas ◽

Chemotherapy Response ◽

High Grade ◽

Expression Quantitative Trait Loci ◽

Platinum Based Chemotherapy ◽

Trait Loci

AbstractBackgroundA major impediment in the treatment of ovarian cancer is the relapse of platinum-resistant tumors, which occurs in approximately 25% of patients. A better understanding of the biological mechanisms underlying platinum-based response will improve treatment efficacy through genetic testing and novel therapies.MethodsUsing data from high-grade serous ovarian carcinoma (HGSOC) patients in the Cancer Genome Atlas (TCGA), we classified those who remained progression-free for 12 months following platinum-based chemotherapy as “chemo-sensitive” (N=160) and those who had recurrence within six months as “chemo-resistant” (N=110). Univariate and multivariate analysis of expression microarrays identified differentially expressed genes and co-expression gene networks associated with chemotherapy response. Moreover, we integrated genomics data to determine expression quantitative trait loci (eQTL).ResultsDifferential expression of the Valosin-containing protein (VCP) gene and five co-expression gene networks were associated with chemotherapy response in HGSOC. VCP and the gene networks contribute to protein processing in the endoplasmic reticulum, which has been implicated in chemotherapy response. These findings were successfully replicated using independent replication cohort. Furthermore, 192 QTLs were associated with these gene networks and BRCA2 expression.ConclusionThis study implicates both known and novel genes as well as biological networks underlying response to platinum-based chemotherapy among HGSOC patients.

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Application of Aegilops tauschii–Triticum aestivum recombinant inbred lines for grain protein content quantitative trait loci detection and wheat improvement

Canadian Journal of Plant Science ◽

10.1139/cjps-2019-0225 ◽

2020 ◽

Vol 100 (4) ◽

pp. 425-434

Author(s):

Yarui Su ◽

Pingan Liao ◽

Danyang Song ◽

Shiquan Huang ◽

Jie He ◽

...

Keyword(s):

Triticum Aestivum ◽

Quantitative Trait Loci ◽

Protein Content ◽

Quantitative Trait ◽

Recombinant Inbred ◽

Recombinant Inbred Lines ◽

Aegilops Tauschii ◽

Grain Protein Content ◽

Inbred Lines ◽

Quality Traits

Grain protein content (GPC) is an important nutritional quality trait of wheat. Aegilops tauschii Coss. is a progenitor of common wheat and has been shown to have high GPC. The objective of this study was to identify quantitative trait loci (QTL) for GPC using A. tauschii–Triticum aestivum L. recombinant lines. An advanced BC2F6 population (112 lines) containing A. tauschii segments was developed using synthetic octaploid wheat (hexaploid wheat Zhoumai 18 × A. tauschii T093), which displayed significant phenotype variances. Two quality traits, GPC and wet gluten, and four yield-related traits, thousand kernel weight, spikelet number per plant, grain number per spike, and grain weight per spike, were evaluated. The results show that the mean GPCs of these lines were significantly higher than those of Zhoumai 18. Correlation and mapping analyses indicated that quality traits were weakly negatively correlated with yield traits. Furthermore, 16 A. tauschii-derived QTL for GPC were detected in the recombinant inbred lines, and four stable QTL that have no significant negative effects on yield and are located within the same marker interval were detected in both environments. Additionally, high-protein, high-yield lines 150228 and 150368 with stable QTL were obtained, and both can be directly utilised for fine mapping of the GPC genes and molecular marker–assisted selection to achieve synergistic improvement of wheat yield and protein content.

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