Power calculation prior to a genetic experiment can help investigators choose the optimal sample size to detect a quantitative trait locus (QTL). Without the guidance of power analysis, an experiment ...may be underpowered or overpowered. Either way will result in wasted resource. QTL mapping and genome-wide association studies (GWAS) are often conducted using a linear mixed model (LMM) with controls of population structure and polygenic background using markers of the whole genome. Power analysis for such a mixed model is often conducted via Monte Carlo simulations. In this study, we derived a non-centrality parameter for the Wald test statistic for association, which allows analytical power analysis. We show that large samples are not necessary to detect a biologically meaningful QTL, say explaining 5% of the phenotypic variance. Several R functions are provided so that users can perform power analysis to determine the minimum sample size required to detect a given QTL with a certain statistical power or calculate the statistical power with given sample size and known values of other population parameters.
Because environmentally degrading inorganic fertilizer use underlies current worldwide cereal yields, future agricultural sustainability demands enhanced nitrogen use efficiency. We found that ...genome-wide promotion of histone H3 lysine 27 trimethylation (H3K27me3) enables nitrogen-induced stimulation of rice tillering: APETALA2-domain transcription factor NGR5 (NITROGEN-MEDIATED TILLER GROWTH RESPONSE 5) facilitates nitrogen-dependent recruitment of polycomb repressive complex 2 to repress branching-inhibitory genes via H3K27me3 modification. NGR5 is a target of gibberellin receptor GIBBERELLIN INSENSITIVE DWARF1 (GID1)-promoted proteasomal destruction. DELLA proteins (characterized by the presence of a conserved aspartate-glutamate-leucine-leucine-alanine motif) competitively inhibit the GID1-NGR5 interaction and explain increased tillering of green revolution varieties. Increased NGR5 activity consequently uncouples tillering from nitrogen regulation, boosting rice yield at low nitrogen fertilization levels. NGR5 thus enables enhanced nitrogen use efficiency for improved future agricultural sustainability and food security.
Genomic Selection (GS) has been proved to be a powerful tool for estimating genetic values in plant and livestock breeding. Newly developed sequencing technologies have dramatically reduced the cost ...of genotyping and significantly increased the scale of genotype data that used for GS. Meanwhile, state-of-the-art statistical methods were developed to make the best use of high marker density genotype data. In this study, 14 traits from four data sets of three species (maize, cattle, and pig) and five influential factors that affect the prediction accuracy were evaluated, including marker density (from 1 to ~600 k), statistical method (GBLUP-A, GBLUP-AD, and BayesR), minor allele frequency (MAF), heritability, and genetic architecture. Results indicate that in the GBLUP method, higher marker density leads to a higher prediction accuracy. In contrast, BayesR method needs more Monte Carlo Markov Chain (MCMC) iterations to reach the convergence and get reliable prediction values. BayesR outperforms GBLUP in predicting high or medium heritability trait that affected by one or several genes with large effects, while GBLUP performs similarly or slightly better than BayesR in predicting low heritability trait that controlled by a large amount of genes with minor effects. Prediction accuracy of trait with complex genetic architecture can be improved by increasing the marker density. Interestingly, for simple traits that controlled by one or several genes with large effects, higher marker density can cause a lower prediction accuracy if the QTN is included, but leads to a higher prediction accuracy if the QTN is excluded. The quantity of genetic markers with low MAF would not significantly affect the prediction accuracy of GBLUP, but results in a bad prediction accuracy performance of BayesR method. Compared with GBLUP-A, GBLUP-AD didn't show any advantages in capturing the non-additive variance for the traits with high heritability. The factors that affected prediction accuracy are discussed in this study and indicate that a combination of either GBLUP or BayesR method with moderate marker density and favorable polymorphism single nucleotide polymorphisms (SNPs) (~25 k SNPs) would always produce a good and stable prediction accuracy with acceptable breeding and computational costs.
Abstract
To investigate the pathogenesis of a congenital form of hepatic fibrosis, human hepatic organoids were engineered to express the most common causative mutation for Autosomal Recessive ...Polycystic Kidney Disease (ARPKD). Here we show that these hepatic organoids develop the key features of ARPKD liver pathology (abnormal bile ducts and fibrosis) in only 21 days. The ARPKD mutation increases collagen abundance and thick collagen fiber production in hepatic organoids, which mirrors ARPKD liver tissue pathology. Transcriptomic and other analyses indicate that the ARPKD mutation generates cholangiocytes with increased TGFβ pathway activation, which are actively involved stimulating myofibroblasts to form collagen fibers. There is also an expansion of collagen-producing myofibroblasts with markedly increased PDGFRB protein expression and an activated STAT3 signaling pathway. Moreover, the transcriptome of ARPKD organoid myofibroblasts resemble those present in commonly occurring forms of liver fibrosis. PDGFRB pathway involvement was confirmed by the anti-fibrotic effect observed when ARPKD organoids were treated with PDGFRB inhibitors. Besides providing insight into the pathogenesis of congenital (and possibly acquired) forms of liver fibrosis, ARPKD organoids could also be used to test the anti-fibrotic efficacy of potential anti-fibrotic therapies.
Polyploidization and introgression are major events driving plant genome evolution and influencing crop breeding. However, the mechanisms underlying the higher-order chromatin organization of ...subgenomes and alien chromosomes are largely unknown.
We probe the three-dimensional chromatin architecture of Aikang 58 (AK58), a widely cultivated allohexaploid wheat variety in China carrying the 1RS/1BL translocation chromosome. The regions involved in inter-chromosomal interactions, both within and between subgenomes, have highly similar sequences. Subgenome-specific territories tend to be connected by subgenome-dominant homologous transposable elements (TEs). The alien 1RS chromosomal arm, which was introgressed from rye and differs from its wheat counterpart, has relatively few inter-chromosome interactions with wheat chromosomes. An analysis of local chromatin structures reveals topologically associating domain (TAD)-like regions covering 52% of the AK58 genome, the boundaries of which are enriched with active genes, zinc-finger factor-binding motifs, CHH methylation, and 24-nt small RNAs. The chromatin loops are mostly localized around TAD boundaries, and the number of gene loops is positively associated with gene activity.
The present study reveals the impact of the genetic sequence context on the higher-order chromatin structure and subgenome stability in hexaploid wheat. Specifically, we characterized the sequence homology-mediated inter-chromosome interactions and the non-canonical role of subgenome-biased TEs. Our findings may have profound implications for future investigations of the interplay between genetic sequences and higher-order structures and their consequences on polyploid genome evolution and introgression-based breeding of crop plants.
The success of common wheat as a global staple crop was largely attributed to its genomic diversity and redundancy due to the merge of different genomes, giving rise to the major question how ...subgenome-divergent and -convergent transcription is mediated and harmonized in a single cell. Here, we create a catalog of genome-wide transcription factor-binding sites (TFBSs) to assemble a common wheat regulatory network on an unprecedented scale. A significant proportion of subgenome-divergent TFBSs are derived from differential expansions of particular transposable elements (TEs) in diploid progenitors, which contribute to subgenome-divergent transcription. Whereas subgenome-convergent transcription is associated with balanced TF binding at loci derived from TE expansions before diploid divergence. These TFBSs have retained in parallel during evolution of each diploid, despite extensive unbalanced turnover of the flanking TEs. Thus, the differential evolutionary selection of paleo- and neo-TEs contribute to subgenome-convergent and -divergent regulation in common wheat, highlighting the influence of TE repertory plasticity on transcriptional plasticity in polyploid.
In the massive machine-type communication scenario, aiming at the problems of active user detection and channel estimation in the grant-free non-orthogonal multiple access (NOMA) system, new sets of ...non-orthogonal spreading sequences are proposed by using the zero/low correlation zone sequence set with low correlation among multiple sets. The simulation results show that the resulting sequence set has low coherence, which presents reliable performance for channel estimation and active user detection based on compressed sensing. Compared with the traditional Zadoff-Chu (ZC) sequences, the new non-orthogonal spreading sequences have more flexible lengths, and lower peak-to-average power ratio (PAPR) and smaller alphabet size. Consequently, these sequences will effectively solve the problem of high PAPR of time domain signals and are more suitable for low-cost devices in massive machine-type communication.
Summary
Nitrogen (N) plays critical role in plant growth; manipulating N assimilation could be a target to increase grain yield and N use. Here, we show that ABRE‐binding factor (ABF)‐like leucine ...zipper transcription factor TabZIP60 mediates N use and growth in wheat. The expression of TabZIP60 is repressed when the N‐deprived wheat plants is exposed to nitrate. Knock down of TabZIP60 through RNA interference (RNAi) increases NADH‐dependent glutamate synthase (NADH‐GOGAT) activity, lateral root branching, N uptake and spike number, and improves grain yield more than 25% under field conditions, while overexpression of TabZIP60‐6D had the opposite effects. Further investigation shows TabZIP60 binds to ABRE‐containing fragment in the promoter of TaNADH‐GOGAT‐3B and negatively regulates its expression. Genetic analysis reveals that TaNADH‐GOGAT‐3B overexpression overcomes the spike number and yield reduction caused by overexpressing TabZIP60‐6D. As such, TabZIP60‐mediated wheat growth and N use is associated with its negative regulation on TaNADH‐GOGAT expression. These findings indicate that TabZIP60 and TaNADH‐GOGAT interaction plays important roles in mediating N use and wheat growth, and provides valuable information for engineering N use efficiency and yield in wheat.
The ability to use genome-wide association studies (GWAS) for genetic discovery depends upon our ability to distinguish true causative from false positive association signals. Population structure ...(PS) has been shown to cause false positive signals in GWAS. PS correction is routinely used for analysis of human GWAS results, and it has been assumed that it also should be utilized for murine GWAS using inbred strains. Nevertheless, there are fundamental differences between murine and human GWAS, and the impact of PS on murine GWAS results has not been carefully investigated. To assess the impact of PS on murine GWAS, we examined 8223 datasets that characterized biomedical responses in panels of inbred mouse strains. Rather than treat PS as a confounding variable, we examined it as a response variable. Surprisingly, we found that PS had a minimal impact on datasets measuring responses in ≤20 strains; and had surprisingly little impact on most datasets characterizing 21 – 40 inbred strains. Moreover, we show that true positive association signals arising from haplotype blocks, SNPs or indels, which were experimentally demonstrated to be causative for trait differences, would be rejected if PS correction were applied to them. Our results indicate because of the special conditions created by GWAS (the use of inbred strains, small sample sizes) PS assessment results should be carefully evaluated in conjunction with other criteria, when murine GWAS results are evaluated.
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