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Introduction Legume crops are an important source of protein and oil for human health and in fixing atmospheric N2 for soil enrichment. With an objective to accelerate much-needed genetic analyses and breeding applications, draft genome assemblies were generated in several legume crops; many of them are not high quality because they are mainly based on short reads. However, the superior quality of genome assembly is crucial for a detailed understanding of genomic architecture, genome evolution, and crop improvement. Objectives Present study was undertaken with an objective of developing improved chromosome-length genome assemblies in six different legumes followed by their systematic investigation to unravel different aspects of genome organization and legume evolution. Methods We employed in situ Hi-C data to improve the existing draft genomes and performed different evolutionary and comparative analyses using improved genome assemblies. Results We have developed chromosome-length genome assemblies in chickpea, pigeonpea, soybean, subterranean clover, and two wild progenitor species of cultivated groundnut (A. duranensis and A. ipaensis). A comprehensive comparative analysis of these genome assemblies offered improved insights into various evolutionary events that shaped the present-day legume species. We highlighted the expansion of gene families contributing to unique traits such as nodulation in legumes, gravitropism in groundnut, and oil biosynthesis in oilseed legume crops such as groundnut and soybean. As examples, we have demonstrated the utility of improved genome assemblies for enhancing the resolution of “QTL-hotspot” identification for drought tolerance in chickpea and marker-trait associations for agronomic traits in pigeonpea through genome-wide association study. Genomic resources developed in this study are publicly available through an online repository, ‘Legumepedia’. Conclusion This study reports chromosome-length genome assemblies of six legume species and demonstrates the utility of these assemblies in crop improvement. The genomic resources developed here will have significant role in accelerating genetic improvement applications of legume crops.

Genomic heterozygosity, self-incompatibility, and rich-in somatic mutations hinder the molecular breeding efficiency of outcrossing plants.We attempted to develop an efficient integrated strategy to identify quantitative trait loci (QTLs) and trait-associated genes, to develop gene markers, and to construct genomics-assisted prediction (GAP) modes.A novel protocol, bulked segregant analysis tool for out-crossing species (BSATOS), is presented here, which is characterized by taking full advantage of all segregation patterns (including AB × AB markers) and haplotype information. To verify the effectiveness of the protocol in dealing with the complex traits of outbreeding species, three apple cross populations with 9,654 individuals were adopted.By using BSATOS, 90, 60, and 77 significant QTLs were identified successfully and candidate genes were predicted for apple fruit weight (FW), fruit ripening date (FRD), and fruit soluble solid content (SSC), respectively. The gene-based markers were developed and genotyped for 1,396 individuals in a training population, including 145 Malus accessions and 1,251 F1 plants of the three full-sib families. GAP models were trained using marker genotype effect estimates of the training population. The prediction accuracy was 0.7658, 0.6455, and 0.3758 for FW, FRD, and SSC, respectively.The BSATOS and GAP models provided a convenient and efficient methodology for candidate gene mining and molecular breeding in out-crossing plant species. The BSATOS pipeline can be freely downloaded from: https://github.com/maypoleflyn/BSATOS.

The current standard-of-care cytogenetic techniques for the analysis of hematological malignancies include karyotyping, fluorescence in situ hybridization, and chromosomal microarray, which are labor intensive and time and cost prohibitive, and they often do not reveal the genetic complexity of the tumor, demonstrating the need for alternative technology for better characterization of these tumors. Herein, we report the results from our clinical validation study and demonstrate the utility of optical genome mapping (OGM), evaluated using 92 sample runs (including replicates) that included 69 well-characterized unique samples (59 hematological neoplasms and 10 controls). The technical performance (quality control metrics) resulted in 100% first-pass rate, with analytical performance (concordance) showing a sensitivity of 98.7%, a specificity of 100%, and an accuracy of 99.2%. OGM demonstrated robust technical, analytical performance, and interrun, intrarun, and interinstrument reproducibility. The limit of detection was determined to be at 5% allele fraction for aneuploidy, translocation, interstitial deletion, and duplication. OGM identified several additional structural variations, revealing the genomic architecture in these neoplasms that provides an opportunity for better tumor classification, prognostication, risk stratification, and therapy selection. Overall, OGM has outperformed the standard-of-care tests in this study and demonstrated its potential as a first-tier cytogenomic test for hematologic malignancies.

Cultivated peanut (Arachis hypogaea L.) is an important oil crop for human nutrition and is cultivated in100 countries. However, the present knowledge of its genomic diversity, evolution, and loci related to the seed traits is limited.Our study intended to (1) uncover the population structure and the demographic history of peanuts, (2) identify signatures of selection that occurred during peanut improvement breeding, and (3) detect and verify the functions of candidate genes associated with seed traits.We explored the population relationship and the evolution of peanuts using a largescale single nucleotide polymorphism dataset generated from the genome-wide resequencing of 203 cultivated peanuts. Genetic diversity and genomic scan analyses were applied to identify selective loci for genomic-selection breeding. Genome-wide association studies, transgenic experiments, and RNA-seq were employed to identify the candidate genes associated with seed traits.Our study revealed that the 203 resequenced accessions were divided into four genetic groups, consistent with their botanical classification. Moreover, the var. peruviana and var. fastigiata subpopulations have diverged to a greater extent than the others, and var. peruviana may be the earliest variant in the evolution from tetraploid ancestors. A recent dramatic expansion in the effective population size of the cultivated peanuts ca. 300-500 years ago was also noted. Selective sweeps underlying quantitative trait loci and genes of seed size, plant architecture, and disease resistance coincide with the major goals of improved peanut breeding compared with the landrace and cultivar populations. Genome-wide association testing with functional analysis led to the identification of two genes involved in seed weight and seed length regulation.Our study provides valuable information for understanding the genomic diversity and the evolution of peanuts and serves as a genomic basis for improving peanut cultivars.

Transposable elements are known by many names, including 'transposons', 'interspersed repeats', 'selfish genetic elements', 'jumping genes', and 'parasitic DNA', but here we will refer to them simply as transposable elements. Many biologists will have heard of transposable elements and their ability to transpose (change position) within the genome. But fewer may be aware of their varied influences on host biology, including contributions to the evolution of diverse host traits such as internal gestation, memory, colouration, and adaptive immunity. Transposable elements are a near ubiquitous feature of eukaryotic genomes, and they often comprise a substantial proportion of total genomic content. Consequently, transposable element genes are considered among the most abundant coding sequences in nature. Recent advances in genome sequencing have ushered in a golden age for transposable-element research, providing opportunities to greatly improve our understanding of the effects of transposable elements on host evolution and disease. However, our ability to detect and analyse transposable elements still faces significant challenges, impairing efforts to decipher their evolution, characterise their diversity, and elucidate their myriad host influences. Below, we summarise key aspects of transposable element biology in eukaryotes and discuss major outstanding research questions.

Wild emmer wheat (Triticum dicoccoides, WEW) is an immediate progenitor of both the cultivated tetraploid and hexaploid wheats and it harbors rich genetic diversity against powdery mildew caused by Blumeria graminis f. sp. tritici (Bgt). A powdery mildew resistance gene MlIW172 originated from WEW accession IW172 (G-797-M) is fine mapped in a 0.048 centimorgan (cM) genetic interval on 7AL, corresponding to a genomic region spanning 233 kb, 1 Mb and 800 kb in Chinese Spring, WEW Zavitan, and T. urartu G1812, respectively. MlIW172 encodes a typical NLR protein NLR

Recent advances in high-throughput chromatin conformation capture (Hi-C) technologies at the single-cell level enable the identification of cell type-specific chromatin loops directly from complex tissues. This may help to interpret noncoding variants identified by genome-wide association studies (GWAS) in disease-relevant cell types. We briefly review current experimental and computational strategies for mapping chromatin loops in single cells.

This study aimed to estimate the cost-effectiveness of exome sequencing (ES) and genome sequencing (GS) for children.We modeled costs, diagnoses, and quality-adjusted life years (QALYs) for diagnostic strategies for critically ill infants (aged1 year) and children (aged18 years) with suspected genetic conditions: (1) standard of care (SOC) testing, (2) ES, (3) GS, (4) SOC followed by ES, (5) SOC followed by GS, (6) ES followed by GS, and (7) SOC followed by ES followed by GS. We calculated the 10-year incremental cost per additional diagnosis, and lifetime incremental cost per QALY gained, from a health care perspective.First-line GS costs $15,048 per diagnosis vs SOC for infants and $27,349 per diagnosis for children. If GS is unavailable, ES represents the next most efficient option compared with SOC ($15,543 per diagnosis for infants and $28,822 per diagnosis for children). Other strategies provided the same or fewer diagnoses at a higher incremental cost per diagnosis. Lifetime results depend on the patient's assumed long-term prognosis after diagnosis. For infants, GS ranged from cost-saving (vs all alternatives) to $18,877 per QALY (vs SOC). For children, GS (vs SOC) ranged from $119,705 to $490,047 per QALY.First-line GS may be the most cost-effective strategy for diagnosing infants with suspected genetic conditions. For all children, GS may be cost-effective under certain assumptions. ES is nearly as efficient as GS and hence is a viable option when GS is unavailable.

Southern corn rust (SCR), caused by the fungal pathogen Puccinia polysora, is a major threat to maize production worldwide. Efficient breeding and deployment of resistant hybrids are key to achieving durable control of SCR. Here, we report the molecular cloning and characterization of RppC, which encodes an NLR-type immune receptor and is responsible for a major SCR resistance quantitative trait locus. Furthermore, we identified the corresponding avirulence effector, AvrRppC, which is secreted by P. polysora and triggers RppC-mediated resistance. Allelic variation of AvrRppC directly determines the effectiveness of RppC-mediated resistance, indicating that monitoring of AvrRppC variants in the field can guide the rational deployment of RppC-containing hybrids in maize production. Currently, RppC is the most frequently deployed SCR resistance gene in China, and a better understanding of its mode of action is critical for extending its durability.

Genome sequencing (GS) can aid clinical management of multiple pediatric conditions. Insurers require accurate cost information to inform funding and implementation decisions. The objective was to compare the laboratory workflows and microcosts of trio GS testing in children with developmental delay (DD) and in children with cardiac conditions.Cost items related to each step in trio GS (child and 2 parents) for both populations were identified and measured. Program costs over 5 years were estimated. Probabilistic and deterministic analyses were conducted.The mean cost per trio GS was CAD$6634.11 (95% CI = 6352.29-6913.40) for DD and CAD$8053.10 (95% CI = 7699.30-8558.10) for cardiac conditions. The 5-year program cost was CAD$28.11 million (95% CI = 26.91-29.29) for DD and CAD$5.63 million (95% CI = 5.38-5.98) for cardiac conditions. Supplies constituted the largest cost component for both populations. The higher cost per sample for the population with cardiac conditions was due to the inclusion of pharmacogenomics, higher bioinformatics labor costs, and a more labor intensive case review.This analysis indicated important variation in trio GS workflow and costs between pediatric populations in a single institution. Enhanced understanding of the clinical utility and costs of GS can inform harmonization and implementation decision-making.

PURPOSE: SouthSeq is a translational research study that performed genome sequencing (GS) for infants with symptoms suggestive of a genetic disorder. Recruitment targeted racial/ethnic minorities and rural, medically underserved areas in the Southeastern US that are historically under-represented in genomic medicine research. METHODS: GS and analysis were performed for 367 infants to detect disease-causal variation concurrent with standard of care evaluation and testing. RESULTS: Definitive diagnostic (DD) or likely diagnostic (LD) genetic findings were identified in 30% of infants and 14% harbored an uncertain result. Only 43% of DD/LD findings were identified via concurrent clinical genetic testing suggesting that GS testing is better for obtaining early genetic diagnosis. We also identified phenotypes that correlate with the likelihood of receiving a DD/LD finding, such as craniofacial, ophthalmologic, auditory, skin, and hair abnormalities. We did not observe any differences in diagnostic rates between racial/ethnic groups. CONCLUSION: We describe one of the largest-to-date GS cohorts of ill infants, enriched for African American and rural patients. Our results demonstrate the utility of GS as it provides early in life detection of clinically relevant genetic variation not identified via current clinical genetic testing, particularly for infants exhibiting certain phenotypic features.

A population of chromosome segment substitution lines was developed using KDML105 as the recurrent parent and one of DH212 (IR68586-F2-CA-143) or DH103 (IR68586-F2-CA-31) as the donor parent. The donor parents are part of a doubled haploid population from a cross between CT9993, an upland japonica accession, and IR62266, a lowland indica accession. Multiple QTL that are relevant to drought avoidance, drought tolerance and yield traits under drought stress were mapped in this doubled haploid population and the segments selected for the chromosome segment substitution lines were chosen to capture these QTL. The chromosome segment substitution line population was phenotyped under irrigated and mild drought stress conditions, which identified that many yield traits under drought stress had been introduced into the chromosome segment substitution lines.

Mitogen-activated protein kinases (MPKs) are important in regulating plant development and stress response. Rapid activation of MPKs in plants usually depends on its phosphorylated. In view of this situation, a phosphorylated GhNTF6 belonged to MPKs family was screened in cotton roots under Verticillium dahliae challenge by phosphoproteomics analysis. Expression of GhNTF6 in cotton plants was did not induce by V. dahliae infection, while, silencing GhNTF6 results to enhance cotton plants susceptibility to V. dahliae, overexpression - GhNTF6 enhance Arabidopsis plants survivability to V. dahliae. Moreover, the mutation of GhNTF6 at site Thr195 and Thy197 with the phosphorylation decreased the plant resistance to V. dahliae. Therefore, GhNTF6 phosphorylation is important in plants against V. dahliae. Further analysis demonstrated that GhNTF6 interacted with a V. dahliae endopolygalacturonase (VdEPG1) on the cell nucleus. We propose that GhNTF6 is a potential molecular target for improving resistance to Verticillium wilt in cotton.

The molecular diagnosis of facioscapulohumeral muscular dystrophy (FSHD) relies on detecting contractions of the unique D4Z4 repeat array at the chromosome 4q35 locus in the presence of a permissive 4q35A haplotype. Long, intact DNA molecules are required for accurate sizing of D4Z4 repeats. We validated the use of optical genome mapping to determine size and haplotype of D4Z4 alleles for FSHD analysis. The cohort included 36 unique DNA specimens from fresh blood samples or archived agarose plugs. High-molecular- weight DNA underwent sequence-specific labeling followed by separation and image analysis with data collection on the Saphyr system. D4Z4 allele sizes were calculated and haplotypes determined from the labeling patterns. Each specimen had previous diagnostic testing using restriction enzyme digests with EcoRI, EcoRI/BlnI, XapI, or HindIII, followed by pulsed field gel electrophoresis and Southern blot analysis with appropriate probes. Optical genome mapping detected 4q35 and 10q26 alleles ranging from 1 to 79 D4Z4 repeats and showed strong correlation with Southern blot allele sizing (R(2) = 0.95) and haplotyping (133 of 134; 99.4% haplotype match). Analysis of inter-assay and intra-assay runs showed high reproducibility (0.03 to 0.94 %CV). Subsequent optical genome mapping for routine clinical testing from 315 clinical FSHD cases compared favorably with historical result trends. Optical genome mapping is an accurate and highly reproducible method for chromosomal abnormalities associated with FSHD.

Loss of the awn in some cereals, including sorghum, is a key transition during cereal domestication or improvement that has facilitated grain harvest and storage. The genetic basis of awn loss in sorghum during domestication or improvement remains unknown. Here, we identified the awn1 gene encoding a transcription factor with the ALOG domain that is responsible for awn loss during sorghum domestication or improvement. awn1 arose from a gene duplication on chromosome 10 that translocated to chromosome 3, recruiting a new promoter from the neighboring intergenic region filled with “noncoding DNA” and recreating the first exon and intron. awn1 acquired high expression after duplication and represses the elongation of awns in domesticated sorghum. Comparative mapping revealed high collinearity at the awn1 paralog locus on chromosome 10 across cereals, and awn growth and development were successfully reactivated on the rice spikelet by inactivating the rice awn1 ortholog. RNA-seq and DAP-seq revealed that as a transcriptional repressor, AWN1 bound directly to a motif in the regulatory regions of three MADS genes related to flower development and two genes, DL and LKS2, involved in awn development. AWN1 downregulates the expression of these genes, thereby repressing awn elongation. The preexistence of regulatory elements in the neighboring intergenic region of awn1 before domestication implicates that noncoding DNA may serve as a treasure trove for evolution during sorghum adaptation to a changing world. Taken together, our results suggest that gene duplication can rapidly drive the evolution of gene regulatory networks in plants.

Purpose To evaluate the diagnostic yield and clinical relevance of clinical genome sequencing (cGS) as a first genetic test for patients with suspected monogenic disorders. Methods We conducted a prospective randomized study with pediatric and adult patients recruited from genetics clinics at Massachusetts General Hospital who were undergoing planned genetic testing. Participants were randomized into two groups: standard-of-care genetic testing (SOC) only or SOC and cGS. Results Two hundred four participants were enrolled, 202 were randomized to one of the intervention arms, and 99 received cGS. In total, cGS returned 16 molecular diagnoses that fully or partially explained the indication for testing in 16 individuals (16.2% of the cohort, 95% confidence interval [CI] 8.9–23.4%), which was not significantly different from SOC (18.2%, 95% CI 10.6–25.8%, P = 0.71). An additional eight molecular diagnoses reported by cGS had uncertain relevance to the participant's phenotype. Nevertheless, referring providers considered 20/24 total cGS molecular diagnoses (83%) to be explanatory for clinical features or worthy of additional workup. Conclusion cGS is technically suitable as a first genetic test. In our cohort, diagnostic yield was not significantly different from SOC. Further studies addressing other variant types and implementation challenges are needed to support feasibility and utility of broad-scale cGS adoption.

Interpretation of the function of non-coding risk loci for neuropsychiatric disorders and brain-relevant traits via gene expression and alternative splicing quantitative trait locus (e/sQTL) analyses is generally performed in bulk post-mortem adult tissue. However, genetic risk loci are enriched in regulatory elements active during neocortical differentiation, and regulatory effects of risk variants may be masked by heterogeneity in bulk tissue. Here, we map e/sQTLs, and allele-specific expression in cultured cells representing two major developmental stages, primary human neural progenitors (n = 85) and their sorted neuronal progeny (n = 74), identifying numerous loci not detected in either bulk developing cortical wall or adult cortex. Using colocalization and genetic imputation via transcriptome-wide association, we uncover cell-type-specific regulatory mechanisms underlying risk for brain-relevant traits that are active during neocortical differentiation. Specifically, we identified a progenitor-specific eQTL for CENPW co-localized with common variant associations for cortical surface area and educational attainment.

The three-dimensional (3D) organization of the genome is highly dynamic, changing during development and varying across different tissues and cell types. Recent studies indicate that these changes alter regulatory interactions, leading to changes in gene expression. Despite its importance, the mechanisms that influence genomic organization remain poorly understood. We have previously identified a network of chromatin boundary elements, or insulators, in the Drosophila Antennapedia homeotic complex (ANT-C). These genomic elements interact with one another to tether chromatin loops that could block or promote enhancer-promoter interactions. To understand the function of these insulators, we assessed their interactions by measuring their 3D nuclear distance in developing animal tissues. Our data suggest that the ANT-C Hox complex might be in a folded or looped configuration rather than in a random or extended form. The architecture of the ANT-C complex, as read out by the pair-wise distance between insulators, undergoes a strong compression during late embryogenesis, coinciding with the reduction of cell and nuclear diameters due to continued cell divisions in post-cleavage cells. Our results suggest that genomic architecture and gene regulation may be influenced by cellular morphology and movement during development.

Members of DOMAIN OF UNKNOWN FUNCTION 679 membrane protein (DMP) gene family, a type of plant-specific membrane proteins, have been proposed to function in various physiological processes such as reproductive development and senescence in plants. Here, a total of 174 DMP genes were identified and analyzed in 16 plant species (including 58 DMPs in four cotton species). Phylogenetic analysis showed that these DMPs could be clustered into five subfamilies (I-V). 137 duplicated cotton gene pairs were identified and most duplicate events were formed by whole-genome duplication (WGD)/segmental duplications. Expression analysis revealed that most of cotton DMPs were mainly expressed in the reproductive organs (the sepal, petal, pistil and anther) and the fiber of secondary cell wall stage. GhDMPs promoter regions containing the different cis-elements also showed different responses to abiotic stress. In addition, gene interaction networks showed that DMPs, as an endomembrane system, were involved in plant senescence process and flower reproductive development. We speculated GhDMP8-A/-D, GbDMP8-A/-D could be used as some candidate gene for inducing cotton haploid. This genome-wide study provides a systematic analysis of the cotton DMP gene family, and further insights towards understanding the potential functions of candidate genes.

The high-quality reference-grade genome for Gossupium tomentosum can greatly promote the progress in biological research and introgression breeding for the mainly cultivated species, G. hirsutum. Here, we report a high-quality genome assembly for G. tomentosum by integrating PacBio and Hi-C technologies. Comparative genomic analysis revealed a large number of genetic variations. Two re-sequencing-based ultra-dense genetic maps were constructed which comprised 4,047,199 and 6,009,681 SNPs, 4120 and 4599 bins and covering 4126.36 cM and 4966.72 cM in the EMF2 (F2 from G. hirsutum × G. tomentosum) and GHF2 (F2 from G. hirsutum × G. barbadense). The EMF2 exhibited lower recombination rate at the whole-genome level as compared with GHF2. We mapped 22 and 33 QTL associated with crossover frequency and predicted Gh_MRE11 and Gh_FIGL1 as the candidate genes governing crossover in the EMF2 and GHF2, respectively. We identified 13 significant QTL that regulate the floral transition, and revealed that Gh_AGL18 was associated with the floral transition. Therefore, our study provides a valuable genomic resource to support a better understanding of cotton interspecific cross and recombination landscape for genetic improvement and breeding in cotton.

Traditionally, filamentous fungi and actinomycetes are well-known cellulolytic microorganisms that have been utilized in the commercial production of cellulase enzyme cocktails for industrial-scale degradation of plant biomass. Noticeably, the Ktedonobacteria lineage (phylum Chloroflexi) with actinomycetes-like morphology was identified and exhibited diverse carbohydrate utilization or degradation abilities. In this study, we performed genome-wide profiling of carbohydrate-active enzymes (CAZymes) in the filamentous Ktedonobacteria lineage. Numerous CAZymes (153–290 CAZymes, representing 63–131 glycoside hydrolases (GHs) per genome), including complex mixtures of endo- and exo-cellulases, were predicted in 15 available Ktedonobacteria genomes. Of note, 4–28 CAZymes were predicted to be extracellular enzymes, whereas 3–29 CAZymes were appended with carbohydrate-binding modules (CBMs) that may promote their binding to insoluble carbohydrate substrates. This number far exceeded other Chloroflexi lineages and were comparable to the cellulolytic actinomycetes. Six multi-modular extracellular GHs were cloned from the thermophilic Thermosporothrix hazakensis SK20-1T strain and heterologously expressed. The putative endo-glucanases of ThazG5-1, ThazG9, and ThazG12 exhibited strong cellulolytic activity, whereas the putative exo-glucanases ThazG6 and ThazG48 formed weak but observable halos on carboxymethyl cellulose plates, indicating their potential biotechnological application. The purified recombinant ThazG12 had near-neutral pH (optimal 6.0), high thermostability (60°C), and broad specificity against soluble and insoluble polysaccharide substrates. It also represented described a novel thermostable bacterial β-1,4-glucanase in the GH12 family. Together, this research revealed the underestimated cellulolytic potential of the Ktedonobacteria lineage and highlighted its potential biotechnological utility as a promising microbial resource for the discovery of industrially useful cellulases.

Young et al. examine the complexity of primary human microglia, and identify previously unknown cell states. Using expression quantitative trait locus (eQTL) mapping techniques, they identify 129 genes whose expression in microglia is linked to disease, and show that induced pluripotent stem cell (iPSC) models can be used for functional validation of common genetic mutations in microglia-associated diseases.

High-throughput genome-wide chromatin conformation capture assay (Hi-C) is routinely used to profile long-range genomic interactions and three-dimensional organization of genomes. A key application of Hi-C is the comparative analysis of genomic interactions across different time points, cellular conditions, or multiple stimuli. While operating characteristics of methods for Hi-C data processing such as normalization, pairwise interaction and higher-order organization detection have been relatively well studied, properties of methods for differential chromatin interaction detection are less investigated. We have recently developed FreeHi-C to enable data-driven non-parametric simulations from Hi-C experiments. Here, we extend FreeHi-C with a user/data-driven spike-in module to facilitate comparisons of differential chromatin interaction detection methods where the ground truth differential chromatin interactions are known under a wide variety of settings. We use FreeHi-C to benchmark four differential chromatin interaction detection methods, namely HiCcompare, multiHiCcompare, diffHic, and Selfish, using three comparative analysis settings with different sequencing depths and spike-in proportions. This comparison reveals distinguished performances in terms of the standard metrics such as the false discovery rate control, detection power, significance order, precision-recall curve, and receiver operating characteristic curve as well as overall genomic properties of the types of differential chromatin interactions detectable by each method. Furthermore, it highlights the lack of power for all methods in small replication settings.

The present study demonstrated a de novo correlation among fiber quality genes in multiple RIL populations including sGK9708 × 0–153, LMY22 × LY343 and Lumianyan28 × Xinluzao24. The current study was conducted to identify the major common QTLs including fiber length and strength, and to identify the co-expression networks of fiber length and strength QTLs harbored genes to target the hub genes. The RNA-seq data of sGK9708 × 0–153 population highlighted 50 and 48 candidate genes of fiber length and fiber strength QTLs. A total of 29 and 21 hub genes were identified in fiber length and strength co-expression network modules. The absolute values of correlation coefficient close to 1 resulted highly positive correlation among hub genes. Results also suggested that the gene correlation significantly influence the gene expression at different fiber development stages. These results might provide useful reference for further experiments in multiple RIL populations and suggest potential candidate genes for functional studies in cotton.

Many important crops (e.g., tuber, root, and tree crops) are cross-pollinating. For these crops, no inbred lines are available for genetic study and breeding because they are self-incompatible, clonally propagated, or have a long generation time, making the identification of agronomically important genes difficult, particularly in crops with a complex autopolyploid genome. In this study, we developed a method, OutcrossSeq, for mapping agronomically important loci in outcrossing crops based on whole-genome low-coverage resequencing of a large genetic population, and designed three computation algorithms in OutcrossSeq for different types of outcrossing populations. We applied OutcrossSeq to a tuberous root crop (sweet potato, autopolyploid), a tree crop (walnut tree, highly heterozygous diploid), and hybrid crops (double-cross populations) to generate high-density genotype maps for the outcrossing populations, which enable precise identification of genomic loci underlying important agronomic traits. Candidate causative genes at these loci were detected based on functional clues. Taken together, our results indicate that OutcrossSeq is a robust and powerful method for identifying agronomically important genes in heterozygous species, including polyploids, in a cost-efficient way. The OutcrossSeq software and its instruction manual are available for downloading at www.xhhuanglab.cn/tool/OutcrossSeq.html .

Rice grain oil is a valuable nutrient source. However, the genetic basis of oil biosynthesis in rice grains remains unclear. In this study, we performed a genome-wide association study on oil composition and oil concentration in a diverse panel of 533 cultivated rice accessions. High variation for 11 oil-related traits was observed, and the oil composition of rice grains showed differentiation among the subpopulations. We identified 46 loci that are significantly associated with grain oil concentration or composition, 16 of which were detected in three recombinant inbred line populations. Twenty-six candidate genes encoding enzymes involved in oil metabolism were identified from these 46 loci, four of which (PAL6, LIN6, MYR2, and ARA6) were found to contribute to natural variation in oil composition and to show differentiation among the subpopulations. Interestingly, population genetic analyses revealed that specific haplotypes of PAL6 and LIN6 have been selected in japonica rice. Based on these results, we propose a possible oil biosynthetic pathway in rice grains. Collectively, our results provide new insights into the genetic basis of oil biosynthesis in rice grains and can facilitate marker-based breeding of rice varieties with enhanced oil and grain quality.

Background & Aims Inflammatory bowel disease (IBD) is a polygenic disorder characterized principally by dysregulated inflammation impacting the gastrointestinal tract. However, there also is increasing evidence for a clinical association with stress and depression. Given the role of the hypothalamus in stress responses and in the pathogenesis of depression, useful insights could be gleaned from understanding its genetic role in IBD. Methods We conducted genetic correlation analyses on publicly available genome-wide association study summary statistics for depression and IBD traits to identify genetic commonalities. We used partitioned linkage disequilibrium score regression, leveraging our ATAC sequencing and promoter-focused Capture C data, to measure enrichment of IBD single-nucleotide polymorphisms within promoter-interacting open chromatin regions of human embryonic stem cell-derived hypothalamic-like neurons (HNs). Using the same data sets, we performed variant-to-gene mapping to implicate putative IBD effector genes in HNs. To contrast these results, we similarly analyzed 3-dimensional genomic data generated in epithelium-derived colonoids from rectal biopsy specimens from donors without pathologic disease noted at the time of colonoscopy. Finally, we conducted enrichment pathway analyses on the implicated genes to identify putative IBD dysfunctional pathways. Results We found significant genetic correlations (rg) of 0.122 with an adjusted P (Padj) = 1.4 × 10-4 for IBD: rg = 0.122; Padj = 2.5 × 10-3 for ulcerative colitis and genetic correlation (rg) = 0.094; Padj = 2.5 × 10-3 for Crohn’s disease, and significant approximately 4-fold (P = .005) and approximately 7-fold (P = .03) enrichment of IBD single-nucleotide polymorphisms in HNs and colonoids, respectively. We implicated 25 associated genes in HNs, among which CREM, CNTF, and RHOA encode key regulators of stress. Seven genes also additionally were implicated in the colonoids. We observed an overall enrichment for immune and hormonal signaling pathways, and a colonoid-specific enrichment for microbiota-relevant terms. Conclusions Our results suggest that the hypothalamus warrants further study in the context of IBD pathogenesis., Graphical abstract

The unusual chromosome 11q23.3 harboring the apolipoprotein (APO) gene cluster has been well documented for its essential roles in plasma lipid-related traits and atherosclerotic cardiovascular diseases. However, its genetic architecture and the potential biological mechanisms underlying complex phenotypes have not been well assessed. We conducted a study for this target region in a Han Chinese population through a stepwise forward framework based on massive parallel sequencing, association analyses, genetic fine mapping, and functional interpretation. The present study identified new meaningful genetic associations that were not simply determined by statistical significance. In addition to the APOA5 gene, we found robust evidence of the genetic commitments of APOC3 and APOA1 to blood lipids. Several variants with high confidence were prioritized along with the potential biological mechanism interpretations in the wake of adaptive fine-mapping analyses. rs2849174 in the APOC3 enhancer was discovered with an unrivaled posterior probability of causality for triglyceride levels and could mediate APOC3 expression through enhancer activity modulated by a combination of histone modifications and transcription factor accessibility. Similarly, multiple lines of evidence converged in favor of rs3741297 as a causal variant influencing high-density lipoprotein cholesterol. Our findings provided novel insights into this genomic locus in the Chinese population.

Purpose Cost-effectiveness evaluations of first-line genomic sequencing (GS) in the diagnosis of children with genetic conditions are limited by the lack of well-defined comparative cohorts. We sought to evaluate the cost-effectiveness of early GS in pediatric patients with complex monogenic conditions compared with a matched historical cohort. Methods Data, including investigation costs, were collected in a prospective cohort of 92 pediatric patients undergoing singleton GS over an 18-month period (2016-2017) with two of the following: a condition with high mortality, multisystem disease involving three or more organs, or severe limitation of daily function. Comparative data were collected in a matched historical cohort who underwent traditional investigations in the years 2012-2013. Results GS yielded a diagnosis in 42% while traditional investigations yielded a diagnosis in 23% (p = 0.003). A change in management was experienced by 74% of patients diagnosed following GS, compared with 32% diagnosed following traditional investigations. Singleton GS at a cost of AU$3100 resulted in a mean saving per person of AU$3602 (95% confidence interval [CI] AU$2520-4685). Cost savings occurred across all investigation subtypes and were only minimally offset by clinical management costs. Conclusion GS in complex pediatric patients saves significant costs and doubles the diagnostic yield of traditional approaches.

The genus Brassica, family Brassicaceae (Cruciferae), comprises many important species of oil crops, vegetables and medicinal plants including B. rapa, B. oleracea, B. nigra, B. napus, B. juncea, B. carinata. Genomic researches in Brassica species is constrained by polyploidization, mainly due to its complicated genomic structure. However, rapid development of methods for detecting single nucleotide polymorphisms (SNP), such as next generation sequencing and SNP microarray, has accelerated release of reference Brassica species genomes as well as discovery of large numbers and genome-wide SNPs, thus intensifying forward genetics in this genus. In this review, we summarize biological characteristics, classification and various methods for detecting SNPs, focusing on high-throughput techniques. Moreover, we describe the pivotal roles of SNPs in genetic diversity, linkage map construction and QTL mapping, comparative genomics, linkage disequilibrium and genome-wide association studies. These insights are expected to deepen our understanding and guide further advancements in Brassica species research.

The bacterium Xanthomonas oryzae pv. Oryzae (Xoo) causes blight in rice worldwide, resulting in significant crop loss. However, no gene underlying a quantitative trait locus (QTL) for resistance against Xoo has been cloned yet. Here, we report the map-based cloning of a QTL, in which the NBS8R gene confers quantitative resistance to Xoo. NBS8R encodes an NB-ARC protein, which is involved in pathogen/microbe-associated molecular pattern-triggered immunity and whose expression is regulated by non-TAL effector XopQ-inducible Osa-miR1876 through DNA methylation. Sequence analysis of NBS8R in wild rice species and rice cultivars suggests that the Osa-miR1876 binding sites in the 5′ UTR of NBS8R are inserted by chance and have undergone variations with Osa-miR1876 throughout evolution. The interaction between NBS8R and XopQ-inducible Osa-miR1876 is partially in keeping with the zigzag model, revealing that quantitative genes may also follow this model to control the innate immune response or basal disease resistance, and may prove valuable in utilizing the existing landraces that harbor the NBS8R gene but with no Osa-miR1876 binding site in rice breeding for bacterial blight resistance.

Amino acid transporters (AATs), which transport amino acids across cell membranes, play important roles in alleviating plant damage under stresses and in plant growth. To data, little is known about the AAT genes in wheat because of its complex genome. In this study, a total of 296 AAT genes were identified from the latest wheat genome sequence (IWGSC v1.1) and classified into 12 distinct subfamilies based upon their sequence composition and phylogenetic relationship. The expansion of the wheat AAT family was mainly the results of whole-genome duplication (WGD) and tandem events. The unequal expansion of different subfamilies brought new features to TaAATs. TaAATs were highly expressed and exhibited distinct expression patterns in different tissues. On the basis of homology and expression pattern analysis, we identified several wheat AAT family members that may affect grain quality. In addition, TaAAP3, TaATLa2 and TaATLb13 exhibited sustained expression in response to drought and high-temperature stress. These genes are involved in the response of wheat to abiotic stress by regulating the transport and distribution of amino acids. Overall, our results help to understand the complexity of TaAATs and provide a theoretical basis for further identification and utilization of AATs in wheat and other crop species.

DNA methylation is a potential epigenetic mechanism that regulates genome stability, development, and stress mitigation in plants. It is mediated by cytosine-5 DNA methyltransferases (C5-MTases). We identified 52 wheat C5-MTases; and based on domain structure and phylogenetics, these 52 C5-MTases were classified into four sub-families including MET, CMT, DRM and DNMT2; and were distributed on 18 chromosomes. Cis-acting regulatory elements analysis identified abiotic stress-responsive, phytohormone-responsive, development-related and light-related elements in the promoters of TaC5-MTases. We also examined the transcript abundance of TaC5-MTases in different tissues, developmental stages and under abiotic stresses. Notably, most of the TaC5-MTases (TaCMT2, TaCMT3b, TaCMT3c, TaMET1, TaDRM10, TaDNMT2) showed differential regulation of their transcript abundance during drought and heat stress. Overall, the above results provide significant insights into the expression and the probable functions of TaC5-MTases and will also expedite future research programs to explore the mechanisms of epigenetic regulation in wheat.

Extensins (EXTs) are major protein components in plant cell walls that play crucial roles in higher plants. The function of EXTs has been reported in several plants but is limited in tomato, especially in fruit ripening. In this study, we identified 83 EXTs in tomato, and divided them into seven groups. The gene intron-exon structure and protein-motif composition of SlEXTs were similar within each group but different among groups. SlEXT genes showed different expression patterns in roots, leaves, flowers and fruits, and some SlEXT gene expressions in flowers could be regulated by treatments of auxin, gibberellic acid and jasmonic acid. In particular, SlSEXT8 had higher and increased expression during tomato fruit ripening, and its expression could be induced by ethylene, suggesting SlSEXT8 may be involved in tomato fruit softening. The result provides insights into the function of EXTs, and will facilitate to further study EXT roles in tomato fruit ripening.

Introduction Genetic inheritance plays key roles in patients with ataxia and/or spastic paraplegia in consanguineous families. This study aims to clarify the genetic spectrum of patients with autosomal recessive hereditary ataxia and spastic paraplegias (AR-HA/HSPs) in consanguineous families. Methods A total of 36 AR-HA/HSPs consanguineous pedigrees from China were recruited into this study. Next generation sequencing (NGS), guided by homozygosity mapping (HM), was applied to identify the pathogenic variants in known genes or novel candidate genes. Results We totally made molecular diagnosis in 47.2% (17/36) of AR-HA/HSPs families. Among them, 13 AR-HAs carried pathogenic variants in SETX (n = 4), SACS (n = 2), STUB1, HSD17B4, NEU1, ADCK3, TPP1, PLA2G6 and MTCL1, while four AR-HSPs carried pathogenic variants in SPG11, ZFYVE26, ATP13A2 and ABCD1. One homozygous nonsense mutation in MRPS27 was identified in an AR-HA family, which was potentially a novel candidate gene of AR-HA. Conclusion HM and NGS can serve as an efficient molecular diagnostic tool for AR-HA/HSPs in consanguineous families. Our findings provide a better understanding of genetic architecture of AR-HA/HSPs in consanguinity and broaden the clinical-genetic spectrum of the disease.

Rapid diagnostic genomic sequencing recently became feasible for infants in intensive care units (ICUs). However, research regarding parents’ perceived utility, adequacy of consent, and potential harms and benefits is lacking. Herein we report results of parental surveys of these domains from the second Newborn Sequencing in Genomic Medicine and Public Health (NSIGHT2) study, a randomized, controlled trial of rapid diagnostic genomic sequencing of infants in regional ICUs. More than 90% of parents reported feeling adequately informed to consent to diagnostic genomic sequencing. Despite only 23% (27) of 117 infants receiving genomic diagnoses, 97% (156) of 161 parents reported that testing was at least somewhat useful and 50.3% (88/161) reported no decisional regret (median 0, mean 10, range 0–100). Five of 117 families (4.3%) reported harm. Upon follow-up, one (1%) confirmed harm to child and parent related to negative results/no diagnosis, two (2%) reported stress or confusion, and two (2%) denied harm. In 81% (89) of 111 infants, families and clinicians agreed that genomic results were useful. Of the families for whom clinicians perceived harm from genomic testing, no parents reported harm. Positive tests/genomic diagnosis were more frequently perceived to be useful by parents, to benefit their infant, and to help manage potential symptoms (p < .05). In summary, the large majority of parents felt that first-tier, rapid, diagnostic genomic sequencing was beneficial for infants lacking etiologic diagnoses in ICUs. Most parents in this study perceived being adequately informed to consent, understood their child’s results, and denied regret or harm from undergoing sequencing.

Heat shock proteins (HSPs) are important elements of the cellular group of molecular chaperones. Specifically, HSP70 proteins protect cells from being damaged when plants are exposed to environmental stresses. These proteins are catalysts that manage the correct folding of other proteins, and they play a key role in the development of tolerance against biotic and abiotic stresses. In the present study, 113 HSP70 genes were retrieved from the available genome assemblies of four cotton species, including Gossypium hirsutum, G. barbadense, G. arboreum, and G. raimondii. The HSP70 genes were clustered into 11 subfamilies based on phylogeny. One hundred and nine (109) gene duplications were found across these four species. Localization of genes revealed that several HSP70 genes reside in the cytoplasm. Synonymous and non-synonymous substitution rates revealed that functional segregation of HSP70 genes in cotton is due to purifying selection. Furthermore, HSP70 genes in cotton are expressed constitutively during developmental stages. These findings are valuable to understand the complex mechanism of HSP70 gene regulation that occurs in signaling pathways in response to plant stress.

The combination of modelling and experimental advances can provide deep insights for understanding chromatin 3D organization and ultimately its underlying mechanisms. In particular, models of polymer physics can help comprehend the complexity of genomic contact maps, as those emerging from technologies such as Hi-C, GAM or SPRITE. Here we discuss a method to reconstruct 3D structures from Genome Architecture Mapping (GAM) data, based on PRISMR, a computational approach introduced to find the minimal polymer model best describing Hi-C input data from only polymer physics. After recapitulating the PRISMR procedure, we describe how we extended it for treating GAM data. We successfully test the method on a 6 Mb region around the Sox9 gene and, at a lower resolution, on the whole chromosome 7 in mouse embryonic stem cells. The PRISMR derived 3D structures from GAM co-segregation data are finally validated against independent Hi-C contact maps. The method results to be versatile and robust, hinting that it can be similarly applied to different experimental data, such as SPRITE or microscopy distance data.

Background Cohen syndrome (CS) is a rare multi-system autosomal recessive disorder with a high prevalence in the Finnish population. Clinical features of Finnish-type CS are homogeneous, however, in non-Finnish populations, CS diagnosis is challenging due to broad phenotypic variability. Methods We studied a consanguineous family having three affected individuals with clinical features of severe intellectual disability and global developmental delay. Clinical diagnosis of the phenotype could not be established based on the features. Therefore, whole genome SNP genotyping and whole exome sequencing (WES) were performed on DNA samples from affected and unaffected family members. Results Homozygosity mapping identified a shared loss of heterozygosity region on chromosome 8q22.1-q22.3 and WES data analysis revealed an insertion-deletion (indel) mutation (c.11519_11521delCAAinsT) in the VPS13B gene. The indel is predicted to cause a frameshift resulting in a premature termination of the VPS13B protein (NP_060360.3:p.Pro3840Leufs*2). Conclusion VPS13B encodes a giant transmembrane protein called vacuolar protein sorting 13 homolog B. VPS13B is known to play a role in the glycosylation of Golgi proteins and in endosomal-lysosomal trafficking. Moreover, it is thought to function in vesicle mediated transport and sorting of proteins within the cell. The mechanism by which abnormalities of the VPS13B protein lead to the phenotype of CS is currently unknown. Here, in this study, we successfully established a clinical diagnosis of CS cases from a family using genomic analyses. Clinical re-examination of the patients revealed characteristic ocular abnormalities.

Transcriptional dysregulation is a hallmark of prostate cancer (PCa). We mapped the RNA polymerase II–associated (RNA Pol II–associated) chromatin interactions in normal prostate cells and PCa cells. We discovered thousands of enhancer-promoter, enhancer-enhancer, as well as promoter-promoter chromatin interactions. These transcriptional hubs operate within the framework set by structural proteins — CTCF and cohesins — and are regulated by the cooperative action of master transcription factors, such as the androgen receptor (AR) and FOXA1. By combining analyses from metastatic castration-resistant PCa (mCRPC) specimens, we show that AR locus amplification contributes to the transcriptional upregulation of the AR gene by increasing the total number of chromatin interaction modules comprising the AR gene and its distal enhancer. We deconvoluted the transcription control modules of several PCa genes, notably the biomarker KLK3, lineage-restricted genes (KRT8, KRT18, HOXB13, FOXA1, ZBTB16), the drug target EZH2, and the oncogene MYC. By integrating clinical PCa data, we defined a germline-somatic interplay between the PCa risk allele rs684232 and the somatically acquired TMPRSS2-ERG gene fusion in the transcriptional regulation of multiple target genes — VPS53, FAM57A, and GEMIN4. Our studies implicate changes in genome organization as a critical determinant of aberrant transcriptional regulation in PCa.

Centromeric satellite DNA (cen-satDNA) sequences of the Asian swamp eel (Monopterus albus) were characterized. Three GC-rich cen-satDNA sequences were detected as a 233 bp MALREP-A and a 293 bp MALREP-B localized to all chromosomes, and a 293 bp MALREP-C distributed on eight chromosome pairs. Sequence lengths of MALREP-B and MALREP-C were 60 bp larger than that of MALREP-A, showing partial homology with core sequences (233 bp). Size differences between MALREP-A and MALREP-B/C suggest the possible occurrence of two satDNA families. The presence of an additional 60 bp in MALREP-B/C resulted from an ancient dimer of 233 bp monomers and subsequent mutation and homogenization between the two monomers. All MALREPs showed partial homology with transposable elements (TEs), suggesting that the MALREPs originated from the TEs. The MALREPs might have been acquired in the Asian swamp eel, thereby promoting fixation in the species.

In the year 2018, the world witnessed the finale of the race to sequence the genome of the world’s most widely grown crop, the common wheat. Wheat has been known to bear a notoriously large and complicated genome of a polyploidy nature. A decade competition to sequence the wheat genome initiated with a single consortium of multiple countries, taking a conventional strategy similar to that for sequencing Arabidopsis and rice, became ferocious over time as both sequencing technologies and genome assembling methodologies advanced. At different stages, multiple versions of genome sequences of the same variety (e.g., Chinese Spring) were produced by several groups with their special strategies. Finally, 16 years after the rice genome was finished and 9 years after that of maize, the wheat research community now possesses its own reference genome. Armed with these genomics tools, wheat will reestablish itself as a model for polyploid plants in studying the mechanisms of polyploidy evolution, domestication, genetic and epigenetic regulation of homoeolog expression, as well as defining its genetic diversity and breeding on the genome level. The enhanced resolution of the wheat genome should also help accelerate development of wheat cultivars that are more tolerant to biotic and/or abiotic stresses with better quality and higher yield.

Purpose Exome and genome sequencing (ES/GS) are performed frequently in patients with congenital anomalies, developmental delay, or intellectual disability (CA/DD/ID), but the impact of results from ES/GS on clinical management and patient outcomes is not well characterized. A systematic evidence review (SER) can support future evidence-based guideline development for use of ES/GS in this patient population. Methods We undertook an SER to identify primary literature from January 2007 to March 2019 describing health, clinical, reproductive, and psychosocial outcomes resulting from ES/GS in patients with CA/DD/ID. A narrative synthesis of results was performed. Results We retrieved 2654 publications for full-text review from 7178 articles. Only 167 articles met our inclusion criteria, and these were primarily case reports or small case series of fewer than 20 patients. The most frequently reported outcomes from ES/GS were changes to clinical management or reproductive decision-making. Two studies reported on the reduction of mortality or morbidity or impact on quality of life following ES/GS. Conclusion There is evidence that ES/GS for patients with CA/DD/ID informs clinical and reproductive decision-making, which could lead to improved outcomes for patients and their family members. Further research is needed to generate evidence regarding health outcomes to inform robust guidelines regarding ES/GS in the care of patients with CA/DD/ID.

Purpose This study investigated the diagnostic utility of nontargeted genomic testing in patients with pediatric heart disease. Methods We analyzed genome sequencing data of 111 families with cardiac lesions for rare, disease-associated variation. Results In 14 families (12.6%), we identified causative variants: seven were de novo (ANKRD11, KMT2D, NR2F2, POGZ, PTPN11, PURA, SALL1) and six were inherited from parents with no or subclinical heart phenotypes (FLT4, DNAH9, MYH11, NEXMIF, NIPBL, PTPN11). Outcome of the testing was associated with the presence of extracardiac features (p = 0.02), but not a positive family history for cardiac lesions (p = 0.67). We also report novel plausible gene–disease associations for tetralogy of Fallot/pulmonary stenosis (CDC42BPA, FGD5), hypoplastic left or right heart (SMARCC1, TLN2, TRPM4, VASP), congenitally corrected transposition of the great arteries (UBXN10), and early-onset cardiomyopathy (TPCN1). The identified candidate genes have critical functions in heart development, such as angiogenesis, mechanotransduction, regulation of heart size, chromatin remodeling, or ciliogenesis. Conclusion This data set demonstrates the diagnostic and scientific value of genome sequencing in pediatric heart disease, anticipating its role as a first-tier diagnostic test. The genetic heterogeneity will necessitate large-scale genomic initiatives for delineating novel gene–disease associations.

Cancers display intratumoral and intertumoral heterogeneity, which poses challenges to small-molecule intervention. Studying drug responses on a whole-genome and transcriptome level using next-generation sequencing has revolutionized our understanding of how small molecules intervene in cells, which helps us to study and potentially predict treatment outcomes. Some small molecules act directly at the genomic level by targeting DNA or chromatin proteins. Here, we review recent advances in establishing whole-genome and transcriptome maps of small-molecule targets, comprising chromatin components or downstream events. We also describe recent advances in studying drug responses using single-cell RNA and DNA sequencing. Furthermore, we discuss how this fundamental research can be taken forward to devise innovative personalized treatment modalities.

For elucidating phylogenetic relationships among members of the family Cicadellidae, mitogenomes of six members of the subfamily Iassinae, including Batracomorphus lateprocessus, Iassus dorsalis, Krisna concava, Krisna rufimarginata, Gessius rufidorsus, and Trocnadella arisana, were sequenced. The mitogenomes are 14,724-15,356-bp long. Moreover, typical 37 genes in mitogenomes were identified; arrangement of these genes in the studied species was consistent with that in the inferred ancestral insects, except for tRNA genes, with a simple switch between the positions of trnI and trnQ in Trocnadella arisana. Most protein-coding genes in the Iassinae mitogenomes showed typical ATN start codons (ATA/ATT/ATC/ATG) and TAR (TAA/TAG) or an incomplete stop codon T--; ATP8 of all sequenced species showed the start codon TTG. The secondary structures of 16S rRNA and 12S rRNA were predicted. 16S rRNA comprised 6 domains with 43 helices, and 12S rRNA comprised 3 domains with 25 helices. All subfamilies, except Cicadellinae and Evacanthinae, were recovered as monophyletic. As reported previously, treehoppers originated from paraphyletic Cicadellidae. Iassinae and Coelidiinae, Megophthalminae and treehoppers, and Cicadellinae and Evacanthinae were sister groups with high nodal support.

Most existing expression quantitative trait locus (eQTL) mapping studies have been focused on individuals of European ancestry and are underrepresented in other populations including populations with African ancestry. Lack of large-scale well-powered eQTL mapping studies in populations with African ancestry can both impede the dissemination of eQTL mapping results that would otherwise benefit individuals with African ancestry and hinder the comparable analysis for understanding how gene regulation is shaped through evolution. We fill this critical knowledge gap by performing a large-scale in-depth eQTL mapping study on 1,032 African Americans (AA) and 801 European Americans (EA) in the GENOA cohort. We identified a total of 354,931 eSNPs in AA and 371,309 eSNPs in EA, with 112,316 eSNPs overlapped between the two. We found that eQTL harboring genes (eGenes) are enriched in metabolic pathways and tend to have higher SNP heritability compared to non-eGenes. We found that eGenes that are common in the two populations tend to be less conserved than eGenes that are unique to one population, which are less conserved than non-eGenes. Through conditional analysis, we found that eGenes in AA tend to harbor more independent eQTLs than eGenes in EA, suggesting potentially diverse genetic architecture underlying expression variation in the two populations. Finally, the large sample sizes in GENOA allow us to construct accurate expression prediction models in both AA and EA, facilitating powerful transcriptome-wide association studies. Overall, our results represent an important step toward revealing the genetic architecture underlying expression variation in African Americans.

Background Pancreatoblastoma is a rare malignancy that occurs predominantly in children. Less than 50 adult cases, including 17 patients with metastatic disease, have been published to date. Recent outcome data from children with advanced-stage disease suggest an intensive multimodal treatment approach; however, little is known about the most beneficial therapy in adults. Molecular characterization of pancreatoblastoma is limited to a small number of pediatric cases and revealed few recurrent genetic events without immediate clinical relevance. Methods Patients were treated between 2013 and 2018 at a high-volume German university cancer center. Molecular analyses included whole genome, exome, transcriptome, and fusion gene panel sequencing. Molecularly guided treatment recommendations were discussed within a dedicated molecular tumor board (MTB) embedded in a precision oncology program (NCT MASTER). Results We identified four adult patients with metastatic pancreatoblastoma. In three patients, local approaches were combined with systemic treatment. Oxaliplatin-containing protocols showed an acceptable tumor control as well as an adequate toxicity profile. Overall survival was 15, 17, 18 and 24 months, respectively. Three tumors harbored genetic alterations involving the FGFR pathway that included an oncogenic FGFR2 fusion. Conclusion Oxaliplatin-containing chemotherapy seems to be a reasonable approach in adult patients with advanced pancreatoblastoma, whereas the benefit of intensified treatment including local ablative techniques or surgical resection remains unclear. Our finding of FGFR alterations in three of four cases indicates a potential role of FGFR signaling in adult pancreatoblastoma whose clinical significance warrants further study.

Mopane worms are the vernacular designation for the edible caterpillars of the African emperor moths Gonimbrasia belina and Gynanisa maja. Both species, particularly G. belina, are widely harvested in Southern Africa, and their populations are declining. Despite their commercial, nutritional, and cultural importance, their genetic data are currently unavailable. We sequenced two complete mitogenomes from each species using Ion Torrent technology, and identified informative markers in the complete mitogenomes of the two species for use in future studies. Comparing the conspecific mitogenomes allowed the identification of regions with high nucleotide diversity in ATP6, ND1, ND4, ND5, ND6, and CYTB genes. The final panels of markers will allow for the survey of 3117 bp in G. belina, and 3990 bp in Gy. maja. Phylogenetic reconstruction within the family Saturniidae recovered the tribe Bunaeini as monophyletic and basal to Saturniidae, and the tribe Attacini as a monophyletic clade nested within the tribe Saturniini. The G. belina and Gy. maja mitogenomes are the first representatives of African Saturniidae, a taxonomic group with relevance as a food resource on the continent. This study represents the first step towards assessing the genetic diversity, population structure, and phylogeography of African edible caterpillars.

The rubber tree, Hevea brasiliensis, produces natural rubber that serves as an essential industrial raw material. Here, we present a high-quality reference genome for a rubber tree cultivar GT1 using single-molecule real-time sequencing (SMRT) and Hi-C technologies to anchor the ∼1.47-Gb genome assembly into 18 pseudochromosomes. The chromosome-based genome analysis enabled us to establish a model of spurge chromosome evolution, since the common paleopolyploid event occurred before the split of Hevea and Manihot. We show recent and rapid bursts of the three Hevea-specific LTR-retrotransposon families during the last 10 million years, leading to the massive expansion by ∼65.88% (∼970 Mbp) of the whole rubber tree genome since the divergence from Manihot. We identify large-scale expansion of genes associated with whole rubber biosynthesis processes, such as basal metabolic processes, ethylene biosynthesis, and the activation of polysaccharide and glycoprotein lectin, which are important properties for latex production. A map of genomic variation between the cultivated and wild rubber trees was obtained, which contains ∼15.7 million high-quality single-nucleotide polymorphisms. We identified hundreds of candidate domestication genes with drastically lowered genomic diversity in the cultivated but not wild rubber trees despite a relatively short domestication history of rubber tree, some of which are involved in rubber biosynthesis. This genome assembly represents key resources for future rubber tree research and breeding, providing novel targets for improving plant biotic and abiotic tolerance and rubber production.