Silong Sun

We report the annotation and analysis of the draft genome sequence of Brassica rapa accession Chiifu-401-42, a Chinese cabbage. We modeled 41,174 protein coding genes in the B. rapa genome, which has undergone genome triplication. We used Arabidopsis thaliana as an outgroup for investigating the consequences of genome triplication, such as structural and functional evolution. The extent of gene loss (fractionation) among triplicated genome segments varies, with one of the three copies consistently retaining a disproportionately large fraction of the genes expected to have been present in its ancestor. Variation in the number of members of gene families present in the genome may contribute to the remarkable morphological plasticity of Brassica species. The B. rapa genome sequence provides an important resource for studying the evolution of polyploid genomes and underpins the genetic improvement of Brassica oil and vegetable crops.

Brassica species include both vegetable and oilseed crops, which are very important to the daily life of common human beings. Meanwhile, the Brassica species represent an excellent system for studying numerous aspects of plant biology, specifically for the analysis of genome evolution following polyploidy, so it is also very important for scientific research. Now, the genome of Brassica rapa has already been assembled, it is the time to do deep mining of the genome data.BRAD, the Brassica database, is a web-based resource focusing on genome scale genetic and genomic data for important Brassica crops. BRAD was built based on the first whole genome sequence and on further data analysis of the Brassica A genome species, Brassica rapa (Chiifu-401-42). It provides datasets, such as the complete genome sequence of B. rapa, which was de novo assembled from Illumina GA II short reads and from BAC clone sequences, predicted genes and associated annotations, non coding RNAs, transposable elements (TE), B. rapa genes' orthologous to those in A. thaliana, as well as genetic markers and linkage maps. BRAD offers useful searching and data mining tools, including search across annotation datasets, search for syntenic or non-syntenic orthologs, and to search the flanking regions of a certain target, as well as the tools of BLAST and Gbrowse. BRAD allows users to enter almost any kind of information, such as a B. rapa or A. thaliana gene ID, physical position or genetic marker.BRAD, a new database which focuses on the genetics and genomics of the Brassica plants has been developed, it aims at helping scientists and breeders to fully and efficiently use the information of genome data of Brassica plants. BRAD will be continuously updated and can be accessed through http://brassicadb.org.

Fungal disease meets its match Fusarium head blight (FHB), caused by a fungus, reduces wheat crop yield and introduces toxins into the harvest. From the assembly of the genome of Thinopyrum elongatum , a wild relative of wheat used in breeding programs to improve cultivated wheat, Wang et al. cloned a gene that can address both problems (see the Perspective by Wulff and Jones). The encoded glutathione S -transferase detoxifies the trichothecene toxin and, when expressed in wheat, confers resistance to FHB. Science , this issue p. eaba5435 ; see also p. 822

Facilitated by the rapid progress of high-throughput sequencing technology, a large number of long noncoding RNAs (lncRNAs) have been identified in mammalian transcriptomes over the past few years. LncRNAs have been shown to play key roles in various biological processes such as imprinting control, circuitry controlling pluripotency and differentiation, immune responses and chromosome dynamics. Notably, a growing number of lncRNAs have been implicated in disease etiology. With the increasing number of published lncRNA studies, the experimental data on lncRNAs (e.g. expression profiles, molecular features and biological functions) have accumulated rapidly. In order to enable a systematic compilation and integration of this information, we have updated the NONCODE database (http://www.noncode.org) to version 3.0 to include the first integrated collection of expression and functional lncRNA data obtained from re-annotated microarray studies in a single database. NONCODE has a user-friendly interface with a variety of search or browse options, a local Genome Browser for visualization and a BLAST server for sequence-alignment search. In addition, NONCODE provides a platform for the ongoing collation of ncRNAs reported in the literature. All data in NONCODE are open to users, and can be downloaded through the website or obtained through the SOAP API and DAS services.

Maize is an important crop with a high level of genome diversity and heterosis. The genome sequence of a typical female line, B73, was previously released. Here, we report a de novo genome assembly of a corresponding male representative line, Mo17. More than 96.4% of the 2,183 Mb assembled genome can be accounted for by 362 scaffolds in ten pseudochromosomes with 38,620 annotated protein-coding genes. Comparative analysis revealed large gene-order and gene structural variations: approximately 10% of the annotated genes were mutually nonsyntenic, and more than 20% of the predicted genes had either large-effect mutations or large structural variations, which might cause considerable protein divergence between the two inbred lines. Our study provides a high-quality reference-genome sequence of an important maize germplasm, and the intraspecific gene order and gene structural variations identified should have implications for heterosis and genome evolution.

Lusheng Huang, Jun Ren and colleagues report the genome sequences of 69 pigs, representing 11 geographically distinct breeds and 3 wild boar populations, from within China. They identify loci related to high- and low-latitude adaptation and infer a likely ancient introgression event in northern Chinese pigs. Domestic pigs have evolved genetic adaptations to their local environmental conditions, such as cold and hot climates. We sequenced the genomes of 69 pigs from 15 geographically divergent locations in China and detected 41 million variants, of which 21 million were absent from the dbSNP database. In a genome-wide scan, we identified a set of loci that likely have a role in regional adaptations to high- and low-latitude environments within China. Intriguingly, we found an exceptionally large (14-Mb) region with a low recombination rate on the X chromosome that appears to have two distinct haplotypes in the high- and low-latitude populations, possibly underlying their adaptation to cold and hot environments, respectively. Surprisingly, the adaptive sweep in the high-latitude regions has acted on DNA that might have been introgressed from an extinct Sus species. Our findings provide new insights into the evolutionary history of pigs and the role of introgression in adaptation.

Polyploidization, both ancient and recent, is frequent among plants. A "two-step theory" was proposed to explain the meso-triplication of the Brassica "A" genome: Brassica rapa. By accurately partitioning of this genome, we observed that genes in the less fractioned subgenome (LF) were dominantly expressed over the genes in more fractioned subgenomes (MFs: MF1 and MF2), while the genes in MF1 were slightly dominantly expressed over the genes in MF2. The results indicated that the dominantly expressed genes tended to be resistant against gene fractionation. By re-sequencing two B. rapa accessions: a vegetable turnip (VT117) and a Rapid Cycling line (L144), we found that genes in LF had less non-synonymous or frameshift mutations than genes in MFs; however mutation rates were not significantly different between MF1 and MF2. The differences in gene expression patterns and on-going gene death among the three subgenomes suggest that "two-step" genome triplication and differential subgenome methylation played important roles in the genome evolution of B. rapa.

CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) is an adaptive immune system in bacteria and archaea to defend against invasion from foreign DNA fragments. Recently, it has been developed as a powerful targeted genome editing tool for a wide variety of species. However, its application in maize has only been tested with transiently expressed somatic cells or with a limited number of stable transgenic T0 plants. The exact efficiency and specificity of the CRISPR/Cas system in the highly complex maize genome has not been documented yet. Here we report an extensive study of the well-studied type II CRISPR-Cas9 system for targeted genome editing in maize, with the codon-optimized Cas9 protein and the short non-coding guide RNA generated through a functional maize U6 snRNA promoter. Targeted gene mutagenesis was detected for 90 loci by maize protoplast assay, with an average cleavage efficiency of 10.67%. Stable knockout transformants for maize phytoene synthase gene (PSY1) were obtained. Mutations occurred in germ cells can be stably inherited to the next generation. Moreover, no off-target effect was detected at the computationally predicted putative off-target loci. No significant difference between the transcriptomes of the Cas9 expressed and non-expressed lines was detected. Our results confirmed that the CRISPR-Cas9 could be successfully applied as a robust targeted genome editing system in maize.

Plants can respond to environmental changes with various mechanisms occurred at transcriptional and translational levels. Thus far, there have been relatively extensive understandings of stress responses of plants on transcriptional level, while little information is known about that on translational level. To uncover the landscape of translation in plants in response to drought stress, we performed the recently developed ribosome profiling assay with maize seedlings growing under normal and drought conditions. Comparative analysis of the ribosome profiling data and the RNA-seq data showed that the fold changes of gene expression at transcriptional level were moderately correlated with that of translational level globally (R(2) = 0.69). However, less than half of the responsive genes were shared by transcription and translation under drought condition, suggesting that drought stress can introduce transcriptional and translational responses independently. We found that the translational efficiencies of 931 genes were changed significantly in response to drought stress. Further analysis revealed that the translational efficiencies of genes were highly influenced by their sequence features including GC content, length of coding sequences and normalized minimal free energy. In addition, we detected potential translation of 3063 upstream open reading frames (uORFs) on 2558 genes and these uORFs may affect the translational efficiency of downstream main open reading frames (ORFs). Our study indicates that plant can respond to drought stress with highly dynamic translational mechanism, that acting synergistically with that of transcription.

Banana cultivars (Musa ssp.) are diploid, triploid and tetraploid hybrids derived from Musa acuminata and Musa balbisiana. We presented a high-quality draft genome assembly of M. balbisiana with 430 Mb (87%) assembled into 11 chromosomes. We identified that the recent divergence of M. acuminata (A-genome) and M. balbisiana (B-genome) occurred after lineage-specific whole-genome duplication, and that the B-genome may be more sensitive to the fractionation process compared to the A-genome. Homoeologous exchanges occurred frequently between A- and B-subgenomes in allopolyploids. Genomic variation within progenitors resulted in functional divergence of subgenomes. Global homoeologue expression dominance occurred between subgenomes of the allotriploid. Gene families related to ethylene biosynthesis and starch metabolism exhibited significant expansion at the pathway level and wide homoeologue expression dominance in the B-subgenome of the allotriploid. The independent origin of 1-aminocyclopropane-1-carboxylic acid oxidase (ACO) homoeologue gene pairs and tandem duplication-driven expansion of ACO genes in the B-subgenome contributed to rapid and major ethylene production post-harvest in allotriploid banana fruits. The findings of this study provide greater context for understanding fruit biology, and aid the development of tools for breeding optimal banana cultivars.

Emerging evidence indicates an association between gut microbiome and arthritis diseases including gout. However, how and which gut bacteria affect host urate degradation and inflammation in gout remains unclear. Here we performed a metagenome analysis on 307 fecal samples from 102 gout patients and 86 healthy controls. Gout metagenomes significantly differed from those of healthy controls. The relative abundances of Prevotella, Fusobacterium, and Bacteroides were increased in gout, whereas those of Enterobacteriaceae and butyrate-producing species were decreased. Functionally, gout patients had greater abundances for genes in fructose, mannose metabolism and lipid A biosynthesis, and lower for genes in urate degradation and short chain fatty acid production. A three-pronged association between metagenomic species, functions and clinical parameters revealed that decreased abundances of species in Enterobacteriaceae were associated with reduced amino acid metabolism and environmental sensing, which together contribute to increased serum uric acid and C-reactive protein levels in gout. A random forest classifier based on three gut microbial genes showed high predictivity for gout in both discovery and validation cohorts (0.91 and 0.80 accuracy), with high specificity in the context of other chronic disorders. Longitudinal analysis showed that uric-acid-lowering and anti-inflammatory drugs partially restored gut microbiota after 24-week treatment. Comparative analysis with obesity, type 2 diabetes, ankylosing spondylitis and rheumatoid arthritis indicated that gout metagenomes were more similar to those of autoimmune than metabolic diseases. Our results suggest that gut dysbiosis was associated with dysregulated host urate degradation and systemic inflammation and may be used as non-invasive diagnostic markers for gout.

Genetic imprinting is a specific epigenetic phenomenon in which a subset of genes is expressed depending on their parent-of-origin. Two types of chromatin modifications, DNA methylation and histone modification, are generally believed to be involved in the regulation of imprinting. However, the genome-wide correlation between allele-specific chromatin modifications and imprinted gene expression in maize remains elusive. Here we report genome-wide high resolution allele-specific maps of DNA methylation and histone H3 lysine 27 trimethylation (H3K27me3) in maize endosperm. For DNA methylation, thousands of parent-of-origin dependent differentially methylated regions (pDMRs) were identified. All pDMRs were uniformly paternally hypermethylated and maternally hypomethylated. We also identified 1131 allele-specific H3K27me3 peaks that are preferentially present in the maternal alleles. Maternally expressed imprinted genes (MEGs) and paternally expressed imprinted genes (PEGs) had different patterns of allele-specific DNA methylation and H3K27me3. Allele-specific expression of MEGs was not directly related to allele-specific H3K27me3, and only a subset of MEGs was associated with maternal-specific DNA demethylation, which was primarily located in the upstream and 5' portion of gene body regions. In contrast, allele-specific expression of a majority of PEGs was related to maternal-specific H3K27me3, with a subgroup of PEGs also associated with maternal-specific DNA demethylation. Both pDMRs and maternal H3K27me3 peaks associated with PEGs are enriched in gene body regions. Our results indicate highly complex patterns of regulation on genetic imprinting in maize endosperm.

Glucosinolates (GS) are a group of amino acid-derived secondary metabolites found throughout the Cruciferae family. Glucosinolates and their degradation products play important roles in pathogen and insect interactions, as well as in human health. In order to elucidate the glucosinolate biosynthetic pathway in Brassica rapa, we conducted comparative genomic analyses of Arabidopsis thaliana and B. rapa on a genome-wide level. We identified 102 putative genes in B. rapa as the orthologs of 52 GS genes in A. thaliana. All but one gene was successfully mapped on 10 chromosomes. Most GS genes exist in more than one copy in B. rapa. A high co-linearity in the glucosinolate biosynthetic pathway between A. thaliana and B. rapa was also established. The homologous GS genes in B. rapa and A. thaliana share 59-91% nucleotide sequence identity and 93% of the GS genes exhibit synteny between B. rapa and A. thaliana. Moreover, the structure and arrangement of the B. rapa GS (BrGS) genes correspond with the known evolutionary divergence of B. rapa, and may help explain the profiles and accumulation of GS in B. rapa.

An excess of fecal bile acids (BAs) is thought to be one of the mechanisms for diarrhea-predominant irritable bowel syndrome (IBS-D). However, the factors causing excessive BA excretion remain incompletely studied. Given the importance of gut microbiota in BA metabolism, we hypothesized that gut dysbiosis might contribute to excessive BA excretion in IBS-D. By performing BA-related metabolic and metagenomic analyses in 290 IBS-D patients and 89 healthy volunteers, we found that 24.5% of IBS-D patients exhibited excessive excretion of total BAs and alteration of BA-transforming bacteria in feces. Notably, the increase in Clostridia bacteria (e.g., C. scindens) was positively associated with the levels of fecal BAs and serum 7α-hydroxy-4-cholesten-3-one (C4), but negatively correlated with serum fibroblast growth factor 19 (FGF19) concentration. Furthermore, colonization with Clostridia-rich IBS-D fecal microbiota or C. scindens individually enhanced serum C4 and hepatic conjugated BAs but reduced ileal FGF19 expression in mice. Inhibition of Clostridium species with vancomycin yielded opposite results. Clostridia-derived BAs suppressed the intestinal FGF19 expression in vitro and in vivo. In conclusion, this study demonstrates that the Clostridia-rich microbiota contributes to excessive BA excretion in IBS-D patients, which provides a mechanistic hypothesis with testable clinical implications.

The gut microbiota is closely associated with gastrointestinal (GI) motility disorder, but the mechanism(s) by which bacteria interact with and affect host GI motility remains unclear. In this study, through using metabolomic and metagenomic analyses, an animal model of neonatal maternal separation (NMS) characterized by accelerated colonic motility and gut dysbiosis was used to investigate the mechanism underlying microbiota-driven motility dysfunction.An excess of intracolonic saturated long-chain fatty acids (SLCFAs) was associated with enhanced bowel motility in NMS rats. Heptadecanoic acid (C17:0) and stearic acid (C18:0), as the most abundant odd- and even-numbered carbon SLCFAs in the colon lumen, can promote rat colonic muscle contraction and increase stool frequency. Increase of SLCFAs was positively correlated with elevated abundances of Prevotella, Lactobacillus, and Alistipes. Functional annotation found that the level of bacterial LCFA biosynthesis was highly enriched in NMS group. Essential synthetic genes Fabs were largely identified from the genera Prevotella, Lactobacillus, and Alistipes. Pseudo germ-free (GF) rats receiving fecal microbiota from NMS donors exhibited increased defecation frequency and upregulated bacterial production of intracolonic SLCFAs. Modulation of gut dysbiosis by neomycin effectively attenuated GI motility and reduced bacterial SLCFA generation in the colon lumen of NMS rats.These findings reveal a previously unknown relationship between gut bacteria, intracolonic SLCFAs, and host GI motility, suggesting the importance of SLCFA-producing bacteria in GI motility disorders. Further exploration of this relationship could lead to a precise medication targeting the gut microbiota for treating GI motility disorders.

Broomcorn millet (Panicum miliaceum L.) has strong tolerance to abiotic stresses, and is probably one of the oldest crops, with its earliest cultivation that dated back to ca. ~10,000 years. We report here its genome assembly through a combination of PacBio sequencing, BioNano, and Hi-C (in vivo) mapping. The 18 super scaffolds cover ~95.6% of the estimated genome (~887.8 Mb). There are 63,671 protein-coding genes annotated in this tetraploid genome. About ~86.2% of the syntenic genes in foxtail millet have two homologous copies in broomcorn millet, indicating rare gene loss after tetraploidization in broomcorn millet. Phylogenetic analysis reveals that broomcorn millet and foxtail millet diverged around ~13.1 Million years ago (Mya), while the lineage specific tetraploidization of broomcorn millet may be happened within ~5.91 million years. The genome is not only beneficial for the genome assisted breeding of broomcorn millet, but also an important resource for other Panicum species.

Significance Parkinson’s disease (PD) is the second most common neurodegenerative disorder in the world. Several common and rare genetic risk variants associated with PD pathogenesis have been identified, predominantly in persons of European descent, but the genetic contributions to familial PD are largely unknown for Han Chinese. Here, we present a trio-based study to explore the association between de novo-altered genes and early onset PD in Han Chinese. We found that the 12 genes with de novo mutations were biologically connected to each other and likely to be disease-risk genes. Further analyses using two independent cohorts revealed that NUS1 harbored more rare nonsynonymous variants, and subsequent functional studies on Drosophila proved its potential link to PD pathogenesis.

Colored-grain wheats have received increasing attention owing to their high nutritional values. In this study, we compared the metabolomes of four pigmented wheat cultivars with conventional yellow wheat using an ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS)-based metabolomics approach. A total of 711 metabolites were identified, and considerable differences were observed in the flavonoid and phenylpropanoid metabolites among five samples by orthogonal signal correction and partial least squares-discriminant analysis (OPLS-DA) analysis. These differential metabolites were significantly enriched in the "anthocyanin biosynthesis", "flavones and flavonols biosynthesis", and "flavonoids biosynthesis" pathways. Furthermore, the expression of 9 structural genes and 2 regulatory genes involved in flavonoid biosynthesis pathway were investigated by quantitative real-time PCR (qRT-PCR). Results suggested that blue, red, purple, and black wheat cultivars showed higher transcription levels of structural and regulatory genes in the flavonoid pathway than that of conventional yellow wheat, possibly accounting for the abundant anthocyanin accumulation in the grains of these four cultivars. This study laid a foundation for understanding the accumulation of flavonoids and coloration mechanisms in colored-grain wheats, and provides a theoretical basis for their sufficient utilization.

RNA editing is a posttranscriptional process that is important in mitochondria and plastids of higher plants. All RNA editing-specific trans-factors reported so far belong to PLS-class of pentatricopeptide repeat (PPR) proteins. Here, we report the map-based cloning and molecular characterization of a defective kernel mutant dek39 in maize. Loss of Dek39 function leads to delayed embryogenesis and endosperm development, reduced kernel size, and seedling lethality. Dek39 encodes an E sub-class PPR protein that targets to both mitochondria and chloroplasts, and is involved in RNA editing in mitochondrial NADH dehydrogenase3 (nad3) at nad3-247 and nad3-275. C-to-U editing of nad3-275 is not conserved and even lost in Arabidopsis, consistent with the idea that no close DEK39 homologs are present in Arabidopsis. However, the amino acids generated by editing nad3-247 and nad3-275 are highly conserved in many other plant species, and the reductions of editing at these two sites decrease the activity of mitochondria NADH dehydrogenase complex I, indicating that the alteration of amino acid sequence is necessary for Nad3 function. Our results indicate that Dek39 encodes an E sub-class PPR protein that is involved in RNA editing of multiple sites and is necessary for seed development of maize.

In plants, the mechanism for ecological sympatric speciation (SS) is little known. Here, after ruling out the possibility of secondary contact, we show that wild emmer wheat, at the microclimatically divergent microsite of “Evolution Canyon” (EC), Mt. Carmel, Israel, underwent triple SS. Initially, it split following a bottleneck of an ancestral population, and further diversified to three isolated populations driven by disruptive ecological selection. Remarkably, two postzygotically isolated populations (SFS1 and SFS2) sympatrically branched within an area less than 30 m at the tropical hot and dry savannoid south-facing slope (SFS). A series of homozygous chromosomal rearrangements in the SFS1 population caused hybrid sterility with the SFS2 population. We demonstrate that these two populations developed divergent adaptive mechanisms against severe abiotic stresses on the tropical SFS. The SFS2 population evolved very early flowering, while the SFS1 population alternatively evolved a direct tolerance to irradiance by improved ROS scavenging activity that potentially accounts for its evolutionary fate with unstable chromosome status. Moreover, a third prezygotically isolated sympatric population adapted on the abutting temperate, humid, cool, and forested north-facing slope (NFS), separated by 250 m from the SFS wild emmer wheat populations. The NFS population evolved multiple resistant loci to fungal diseases, including powdery mildew and stripe rust. Our study illustrates how plants sympatrically adapt and speciate under disruptive ecological selection of abiotic and biotic stresses.

Glutathione S-transferases (GSTs) are ancient proteins encoded by a large gene family in plants, which play multiple roles in plant growth and development. However, there has been little study on the GST genes of common wheat (Triticum aestivum) and its relatives (Triticum durum, Triticum urartu, and Aegilops tauschii), which are four important species of Triticeae. Here, a genome-wide comprehensive analysis of this gene family was performed on the genomes of common wheat and its relatives. A total of 346 GST genes in T. aestivum, 226 in T. durum, 104 in T. urartu, and 105 in Ae. tauschii were identified, and all members were divided into ten classes. Transcriptome analysis was used to identify GST genes that respond to salt stress in common wheat, which revealed that the reaction of GST genes is not sensitive to low and moderate salt concentrations but is sensitive to severe concentrations of the stressor, and the GST genes related to salt stress mainly come from the Tau and Phi classes. Six GST genes which respond to different salt concentrations were selected and validated by a qRT-PCR assay. These findings will not only provide helpful information about the function of GST genes in Triticeae species but also offer insights for the future application of salt stress resistance breeding in common wheat.

Treacher Collins Ι syndrome (TCS1, OMIM:154500) is an autosomal dominant disease with a series of clinical manifestations such as craniofacial dysplasia including eye and ear abnormalities, small jaw deformity, cleft lip, as well as repeated respiratory tract infection and conductive hearing loss. Two cases of Treacher Collins syndrome with TCOF1(OMIM:606847) gene variations were reported in the article, with clinical characteristics, gene variants and the etiology.The clinical data of two patients with Treacher Collins syndrome caused by TCOF1 gene variation were retrospectively analyzed. The whole exome sequencing (WES) was performed to detect the pathogenic variants of TCOF1 gene in the patients, and the verification of variants were confirmed by Sanger sequencing.Proband 1 presented with bilateral craniofacial deformities, conductive hearing loss and recurrent respiratory tract infection. Proband 2 showed bilateral craniofacial malformations with cleft palate, which harbored similar manifestations in her family. She died soon after birth due to dyspnea and feeding difficulties. WES identified two novel pathogenic variants of TCOF1 gene in two probands, each with one variant. According to the American College of Medical Genetics and Genomics, the heterozygous variation NM_001371623.1: c.877del (p. Ala293Profs*34) of TCOF1 gene was detected in Proband 1, which was evaluated as a likely pathogenic (LP) and de novo variant. Another variant found in Proband 2 was NM_001135243.1: c.1660_1661del (p. D554Qfs*3) heterozygous variation, which was evaluated as a pathogenic variation and the variant inherited from the mother. To date, the two variants have not been reported before.Our study found two novel pathogenic variants of TCOF1 gene and clarified the etiology of Treacher Collins syndrome. We also enriched the phenotypic spectrum of Treacher Collins syndrome and TCOF1 gene variation spectrum in the Chinese population, and provided the basis for clinical diagnosis, treatment and genetic counseling.

Brassica rapa is an economically important crop and a model plant for studies concerning polyploidization and the evolution of extreme morphology. The multinational B. rapa Genome Sequencing Project (BrGSP) was launched in 2003. In 2008, next generation sequencing technology was used to sequence the B. rapa genome. Several maps concerning B. rapa pseudochromosome assembly have been published but their coverage of the genome is incomplete, anchoring approximately 73.6% of the scaffolds on to chromosomes. Therefore, a new genetic map to aid pseudochromosome assembly is required.This study concerns the construction of a reference genetic linkage map for Brassica rapa, forming the backbone for anchoring sequence scaffolds of the B. rapa genome resulting from recent sequencing efforts. One hundred and nineteen doubled haploid (DH) lines derived from microspore cultures of an F1 cross between a Chinese cabbage (B. rapa ssp. pekinensis) DH line (Z16) and a rapid cycling inbred line (L144) were used to construct the linkage map. PCR-based insertion/deletion (InDel) markers were developed by re-sequencing the two parental lines. The map comprises a total of 507 markers including 415 InDels and 92 SSRs. Alignment and orientation using SSR markers in common with existing B. rapa linkage maps allowed ten linkage groups to be identified, designated A01-A10. The total length of the linkage map was 1234.2 cM, with an average distance of 2.43 cM between adjacent marker loci. The lengths of linkage groups ranged from 71.5 cM to 188.5 cM for A08 and A09, respectively. Using the developed linkage map, 152 scaffolds were anchored on to the chromosomes, encompassing more than 82.9% of the B. rapa genome. Taken together with the previously available linkage maps, 183 scaffolds were anchored on to the chromosomes and the total coverage of the genome was 88.9%.The development of this linkage map is vital for the integration of genome sequences and genetic information, and provides a useful resource for the international Brassica research community.

Large intergenic noncoding RNAs (lincRNAs) have been recognized in recent years to constitute a significant portion of the mammalian transcriptome, yet their biological functions remain largely elusive. This is partly due to an incomplete annotation of tissue-specific lincRNAs in essential model organisms, particularly in mice, which has hindered the genetic annotation and functional characterization of these novel transcripts. In this report, we performed ab initio assembly of 1.9 billion tissue-specific RNA-sequencing reads across six tissue types, and identified 3,965 novel expressed lincRNAs in mice. Combining these with 6,606 documented lincRNAs, we established a comprehensive catalog of 10,571 transcribed lincRNAs. We then systemically analyzed all mouse lincRNAs to reveal that some of them are evolutionally conserved and that they exhibit striking tissue-specific expression patterns. We also discovered that mouse lincRNAs carry unique genomic signatures, and that their expression level is correlated with that of neighboring protein-coding transcripts. Finally, we predicted that a large portion of tissue-specific lincRNAs are functionally associated with essential biological processes including the cell cycle and cell development, and that they could play a key role in regulating tissue development and functionality. Our analyses provide a framework for continued discovery and annotation of tissue-specific lincRNAs in model organisms, and our transcribed mouse lincRNA catalog will serve as a roadmap for functional analyses of lincRNAs in genetic mouse models.

Abstract Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis ( Mtb ), and remains a leading public health problem. Previous studies have identified host genetic factors that contribute to Mtb infection outcomes. However, much of the heritability in TB remains unaccounted for and additional susceptibility loci most likely exist. We perform a multistage genome-wide association study on 2949 pulmonary TB patients and 5090 healthy controls (833 cases and 1220 controls were genome-wide genotyped) from Han Chinese population. We discover two risk loci: 14q24.3 (rs12437118, P combined = 1.72 × 10 −11 , OR = 1.277, ESRRB ) and 20p13 (rs6114027, P combined = 2.37 × 10 −11 , OR = 1.339, TGM6 ). Moreover, we determine that the rs6114027 risk allele is related to decreased TGM6 transcripts in PBMCs from pulmonary TB patients and severer pulmonary TB disease. Furthermore, we find that tgm6 -deficient mice are more susceptible to Mtb infection. Our results provide new insights into the genetic etiology of TB.

Abstract Dendrobium huoshanense is used to treat various diseases in traditional Chinese medicine. Recent studies have identified active components. However, the lack of genomic data limits research on the biosynthesis and application of these therapeutic ingredients. To address this issue, we generated the first chromosome-level genome assembly and annotation of D. huoshanense. We integrated PacBio sequencing data, Illumina paired-end sequencing data, and Hi-C sequencing data to assemble a 1.285 Gb genome, with contig and scaffold N50 lengths of 598 kb and 71.79 Mb, respectively. We annotated 21,070 protein-coding genes and 0.96 Gb transposable elements, constituting 74.92% of the whole assembly. In addition, we identified 252 genes responsible for polysaccharide biosynthesis by Kyoto Encyclopedia of Genes and Genomes functional annotation. Our data provide a basis for further functional studies, particularly those focused on genes related to glycan biosynthesis and metabolism, and have implications for both conservation and medicine.

Attention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous psychiatric disorder that can have three phenotypical presentations: inattentive (I-ADHD), hyperactive-impulsive (HI-ADHD), and combined (C-ADHD). Environmental factors correlated with the gut microbiota community have been implicated in the development of ADHD. However, whether different ADHD symptomatic presentations are associated with distinct microbiota compositions and whether patients could benefit from the correction of aberrant bacterial colonization are still largely unclear. We carried out metagenomic shotgun analysis with 207 human fecal samples to characterize the gut microbial profiles of patients with ADHD grouped according to their phenotypical presentation. Then, we transplanted the candidate low-abundance bacteria identified in patient subgroups into ADHD rats and evaluated ADHD-associated behaviors and neuronal activation in these rats. Patients with C-ADHD had a different gut microbial composition from that of healthy controls (HCs) (p = .02), but not from that of I-ADHD patients. Eight species became progressively attenuated or enriched when comparing the compositions of HCs to those of I-ADHD and C-ADHD; in particular, the abundance of Bacteroides ovatus was depleted in patients with C-ADHD. In turn, Bacteroides ovatus supplementation ameliorated spatial working memory deficits and reversed θ electroencephalogram rhythm alterations in ADHD rats. In addition, Bacteroides ovatus induced enhanced neuronal activation in the hippocampal CA1 subregion. These findings indicate that gut microbial characteristics that are unique to patients with C-ADHD may be masked when considering a more heterogeneous group of patients. We link the gut microbiota to brain function in an ADHD animal model, suggesting the relevance of testing a potential bacteria-based intervention for some aspects of ADHD.

Human MutationVolume 38, Issue 11 p. 1500-1510 RESEARCH ARTICLE Rare coding variants in MAPK7 predispose to adolescent idiopathic scoliosis Correction(s) for this article Rare coding variants in MAPK7 predispose to adolescent idiopathic scoliosis Volume 42Issue 2Human Mutation pages: 218-218 First Published online: December 25, 2020 Wenjie Gao, Wenjie Gao Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Research Centre for Translational Medicine, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Department of Spine Surgery, Xi'an Honghui Hospital, Xi'an Jiaotong University, Xi'an, China Wenjie Gao, Chong Chen, and Taifeng Zhou contributed equally to this work.Search for more papers by this authorChong Chen, Chong Chen Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China Wenjie Gao, Chong Chen, and Taifeng Zhou contributed equally to this work.Search for more papers by this authorTaifeng Zhou, Taifeng Zhou Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Wenjie Gao, Chong Chen, and Taifeng Zhou contributed equally to this work.Search for more papers by this authorShulan Yang, Shulan Yang Research Centre for Translational Medicine, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorBo Gao, Bo Gao Department of Spine Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorHang Zhou, Hang Zhou Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorChengjie Lian, Chengjie Lian Department of Spine Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorZizhao Wu, Zizhao Wu Department of Spine Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorXianjian Qiu, Xianjian Qiu Department of Spine Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorXiaoming Yang, Xiaoming Yang Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorEsam Alattar, Esam Alattar Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorWentao Liu, Wentao Liu Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorDeying Su, Deying Su Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorSilong Sun, Silong Sun BGI-Shenzhen, Shenzhen, ChinaSearch for more papers by this authorYulan Chen, Yulan Chen BGI-Shenzhen, Shenzhen, ChinaSearch for more papers by this authorKenneth M. C. Cheung, Kenneth M. C. Cheung Department of Orthopaedics and Traumatology, Faculty of Medicine, University of Hong Kong, Hong Kong, ChinaSearch for more papers by this authorYouqiang Song, Youqiang Song Department of Biochemistry, Faculty of Medicine, University of Hong Kong, Hong Kong, ChinaSearch for more papers by this authorKeith K. D. Luk, Keith K. D. Luk Department of Orthopaedics and Traumatology, Faculty of Medicine, University of Hong Kong, Hong Kong, ChinaSearch for more papers by this authorDanny Chan, Danny Chan Department of Biochemistry, Faculty of Medicine, University of Hong Kong, Hong Kong, ChinaSearch for more papers by this authorPak Chung Sham, Pak Chung Sham Department of Psychiatry, Faculty of Medicine, University of Hong Kong, Hong Kong, ChinaSearch for more papers by this authorChao Xing, Chao Xing Department of Clinical Sciences, University of Texas Southwestern Medical Centre, Dallas, Texas McDermott Centre for Human Growth & Development, University of Texas Southwestern Medical Centre, Dallas, TexasSearch for more papers by this authorChiea Chuen Khor, Chiea Chuen Khor Division of Human Genetics, Genome Institute of Singapore, Singapore, SingaporeSearch for more papers by this authorGabriel Liu, Gabriel Liu Department of Orthopaedic Surgery, University Spine Centre, National University Hospital, Singapore, SingaporeSearch for more papers by this authorJunlin Yang, Junlin Yang Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorYubin Deng, Yubin Deng Research Centre for Translational Medicine, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorDingjun Hao, Dingjun Hao Department of Spine Surgery, Xi'an Honghui Hospital, Xi'an Jiaotong University, Xi'an, ChinaSearch for more papers by this authorDongsheng Huang, Dongsheng Huang Department of Spine Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorQuan-Zhen Li, Quan-Zhen Li Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Centre, Dallas, Texas Microarray Core & Genomics Facility, University of Texas Southwestern Medical Centre, Dallas, TexasSearch for more papers by this authorCaixia Xu, Corresponding Author Caixia Xu xucx3@mail.sysu.edu.cn Research Centre for Translational Medicine, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Correspondence Peiqiang Su, Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Yuexiu District, Guangzhou 510080, China. Email: supq@mail.sysu.edu.cn Caixia Xu, Research Centre for Translational Medicine, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Yuexiu District, Guangzhou 510080, China. Email: xucx3@mail.sysu.edu.cnSearch for more papers by this authorPeiqiang Su, Corresponding Author Peiqiang Su supq@mail.sysu.edu.cn Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Correspondence Peiqiang Su, Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Yuexiu District, Guangzhou 510080, China. Email: supq@mail.sysu.edu.cn Caixia Xu, Research Centre for Translational Medicine, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Yuexiu District, Guangzhou 510080, China. Email: xucx3@mail.sysu.edu.cnSearch for more papers by this author Wenjie Gao, Wenjie Gao Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Research Centre for Translational Medicine, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Department of Spine Surgery, Xi'an Honghui Hospital, Xi'an Jiaotong University, Xi'an, China Wenjie Gao, Chong Chen, and Taifeng Zhou contributed equally to this work.Search for more papers by this authorChong Chen, Chong Chen Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Department of Orthopaedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China Wenjie Gao, Chong Chen, and Taifeng Zhou contributed equally to this work.Search for more papers by this authorTaifeng Zhou, Taifeng Zhou Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Wenjie Gao, Chong Chen, and Taifeng Zhou contributed equally to this work.Search for more papers by this authorShulan Yang, Shulan Yang Research Centre for Translational Medicine, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorBo Gao, Bo Gao Department of Spine Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorHang Zhou, Hang Zhou Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorChengjie Lian, Chengjie Lian Department of Spine Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorZizhao Wu, Zizhao Wu Department of Spine Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorXianjian Qiu, Xianjian Qiu Department of Spine Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorXiaoming Yang, Xiaoming Yang Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorEsam Alattar, Esam Alattar Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorWentao Liu, Wentao Liu Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorDeying Su, Deying Su Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorSilong Sun, Silong Sun BGI-Shenzhen, Shenzhen, ChinaSearch for more papers by this authorYulan Chen, Yulan Chen BGI-Shenzhen, Shenzhen, ChinaSearch for more papers by this authorKenneth M. C. Cheung, Kenneth M. C. Cheung Department of Orthopaedics and Traumatology, Faculty of Medicine, University of Hong Kong, Hong Kong, ChinaSearch for more papers by this authorYouqiang Song, Youqiang Song Department of Biochemistry, Faculty of Medicine, University of Hong Kong, Hong Kong, ChinaSearch for more papers by this authorKeith K. D. Luk, Keith K. D. Luk Department of Orthopaedics and Traumatology, Faculty of Medicine, University of Hong Kong, Hong Kong, ChinaSearch for more papers by this authorDanny Chan, Danny Chan Department of Biochemistry, Faculty of Medicine, University of Hong Kong, Hong Kong, ChinaSearch for more papers by this authorPak Chung Sham, Pak Chung Sham Department of Psychiatry, Faculty of Medicine, University of Hong Kong, Hong Kong, ChinaSearch for more papers by this authorChao Xing, Chao Xing Department of Clinical Sciences, University of Texas Southwestern Medical Centre, Dallas, Texas McDermott Centre for Human Growth & Development, University of Texas Southwestern Medical Centre, Dallas, TexasSearch for more papers by this authorChiea Chuen Khor, Chiea Chuen Khor Division of Human Genetics, Genome Institute of Singapore, Singapore, SingaporeSearch for more papers by this authorGabriel Liu, Gabriel Liu Department of Orthopaedic Surgery, University Spine Centre, National University Hospital, Singapore, SingaporeSearch for more papers by this authorJunlin Yang, Junlin Yang Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorYubin Deng, Yubin Deng Research Centre for Translational Medicine, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorDingjun Hao, Dingjun Hao Department of Spine Surgery, Xi'an Honghui Hospital, Xi'an Jiaotong University, Xi'an, ChinaSearch for more papers by this authorDongsheng Huang, Dongsheng Huang Department of Spine Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaSearch for more papers by this authorQuan-Zhen Li, Quan-Zhen Li Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Centre, Dallas, Texas Microarray Core & Genomics Facility, University of Texas Southwestern Medical Centre, Dallas, TexasSearch for more papers by this authorCaixia Xu, Corresponding Author Caixia Xu xucx3@mail.sysu.edu.cn Research Centre for Translational Medicine, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Correspondence Peiqiang Su, Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Yuexiu District, Guangzhou 510080, China. Email: supq@mail.sysu.edu.cn Caixia Xu, Research Centre for Translational Medicine, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Yuexiu District, Guangzhou 510080, China. Email: xucx3@mail.sysu.edu.cnSearch for more papers by this authorPeiqiang Su, Corresponding Author Peiqiang Su supq@mail.sysu.edu.cn Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Guangdong Provincial Key Laboratory of Orthopedics and Traumatology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China Correspondence Peiqiang Su, Department of Orthopaedic Surgery, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Yuexiu District, Guangzhou 510080, China. Email: supq@mail.sysu.edu.cn Caixia Xu, Research Centre for Translational Medicine, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Yuexiu District, Guangzhou 510080, China. Email: xucx3@mail.sysu.edu.cnSearch for more papers by this author First published: 17 July 2017 https://doi.org/10.1002/humu.23296Citations: 24 Caixia Xu, Research Centre for Translational Medicine, First Affiliated Hospital, Sun Yat-Sen University, No. 58 Zhongshan 2nd Road, Yuexiu District, Guangzhou 510080, China. Email: xucx3@mail.sysu.edu.cn Contract grant sponsors: National Natural Science Foundation of China (Nos. 81371908, 81472039, 81572091, 81601898); the China Postdoctoral Science Foundation (No. 2017M613177); the Program for New Century Excellent Talents in University (NCET-12-0564); Fundamental Research Funds for the Central Universities; Young Teachers Fund of the Sun Yat-Sen University (13YKPY23). Communicated by Stephen Robertson Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Adolescent idiopathic scoliosis (AIS) is a complex genetic disorder characterized by three-dimensional spinal curvatures, affecting 2%–3% of school age children, yet the causes underlying AIS are not well understood. Here, we first conducted a whole-exome sequencing and linkage analysis on a three-generation Chinese family with autosomal-dominant (AD) AIS, and then performed targeted sequencing in a discovery cohort comprising 20 AD AIS families and 86 simplex patients, and finally identified three disease-associated missense variants (c.886G> A, c.1943C> T, and c.1760C> T) in the MAPK7 gene (encoding mitogen-activated protein kinase 7). Genotyping of the three rare variants in a Chinese replication cohort comprising 1,038 simplex patients and 1,841 controls showed that their combined allele frequency was significantly over-represented in patients as compared with controls (2.0% [41/2,076] vs. 0.7% [27/3,682]; odds ratio = 2.7; P = 2.8 × 10−5). In vitro, we demonstrated that the three MAPK7 mutants disrupted nuclear translocation in cellular models, which is necessary for the normal function of MAPK7. In vivo, we also conducted CRISPR/Cas9-mediated deletion of mapk7 in zebrafish recapitulating the characteristic phenotype of idiopathic scoliosis. Taken together, our findings suggest that rare coding variants in MAPK7 predispose to AIS, providing clues to understanding the mechanisms of AIS. Citing Literature Supporting Information Filename Description humu23296-sup-0001-tableS1-S3.docx22.5 KB Supplemental Table S1. Summary of the 20 potentially deleterious missense variants Supplemental Table S2. Characteristics of the discovery cohort used for targeted sequencing of the MAPK7 gene Supplemental Table S3. Characteristics of the replication cohort used for genotyping the three MAPK7 missense variants Supplemental Table S4. Result of the case-control association study for the MAPK7 c.886G> A variant in replication cohort Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume38, Issue11November 2017Pages 1500-1510 RelatedInformation

Acne is a common chronic skin disease with a multifactorial aetiology and pathogenesis. Recently, circular RNAs (circRNAs) have been identified as a key factor in regulating gene expression through circRNA-miRNA-mRNA networks in many biological processes and human diseases. However, the circRNAs expression in patients with acne is still unknown.To investigate circRNA expression profile in severe acne.The expression profile of circRNAs in three paired lesional skin and adjacent non-lesional skin in severe acne was detected by high-throughput RNA sequencing technology and bioinformatics analysis. The candidate circRNAs were validated by PCR, Sanger sequencing and qRT-PCR in the separate group (n = 4). The circRNA-miRNA-mRNA interaction networks were predicted.A total of 538 circRNAs including 271 up- and 267 downregulated circRNAs were differentially expressed in lesional skin compared with adjacent non-lesional skin in severe acne. Gene Ontology and KEGG pathway enrichment analyses revealed that the aberrantly expressed circRNAs were primarily involved in inflammatory, metabolism and immune responses. Five candidate circRNAs (circRNA_0084927, circRNA_0001073, circRNA_0005941, circRNA_0086376 and circRNA_0018168) were validated to have significant decrease in severe acne by PCR, Sanger sequencing and qRT-PCR, in agreement with the results from RNA-Seq data analysis. The five identified circRNAs were predicted to interact with 213 miRNAs and regulated target gene expression.This study firstly showed that circRNAs were differentially expressed in severe acne and suggested that circRNAs could be used as a potential biomarker for the drug targets of acne.

Genetic studies based on single-nucleotide polymorphisms have provided valuable insights into the genetic architecture of complex diseases. However, a large fraction of heritability for most of these diseases remains unexplained, and the impact of small insertions and deletions (InDels) has been neglected. We performed a comprehensive screen on the exome sequence data of 1,326 genes using the SOAP-PopIndel method for InDels in 32,043 Chinese Han individuals and identified 29 unreported InDels within 25 susceptibility genes associated with psoriasis. Specifically, we identified 12 common, 9 low-frequency, and 8 rare InDels that explained approximately 1.29% of the heritability of psoriasis. Further analyses identified KIAA0319, RELN, NCAPG, ABO, AADACL2, LMAN1, FLG, HERC5, CCDC66, LEKR1, AFF3, ABCG2, ANXA7, SYTL2,GIPR, METTL1, and FYCO1 as unreported genes for psoriasis. In addition, identified InDels were associated with the following reported genes: IFIH1, ERAP1, ERAP2, LNPEP, UBLCP1, and STAT3; unreported independent associations for exonic InDels were found within GJB2 and ZNF816A. Our study enriched the genetic basis and pathogenesis of psoriasis and highlighted the non-negligible impact of InDels on complex human diseases. Genetic studies based on single-nucleotide polymorphisms have provided valuable insights into the genetic architecture of complex diseases. However, a large fraction of heritability for most of these diseases remains unexplained, and the impact of small insertions and deletions (InDels) has been neglected. We performed a comprehensive screen on the exome sequence data of 1,326 genes using the SOAP-PopIndel method for InDels in 32,043 Chinese Han individuals and identified 29 unreported InDels within 25 susceptibility genes associated with psoriasis. Specifically, we identified 12 common, 9 low-frequency, and 8 rare InDels that explained approximately 1.29% of the heritability of psoriasis. Further analyses identified KIAA0319, RELN, NCAPG, ABO, AADACL2, LMAN1, FLG, HERC5, CCDC66, LEKR1, AFF3, ABCG2, ANXA7, SYTL2,GIPR, METTL1, and FYCO1 as unreported genes for psoriasis. In addition, identified InDels were associated with the following reported genes: IFIH1, ERAP1, ERAP2, LNPEP, UBLCP1, and STAT3; unreported independent associations for exonic InDels were found within GJB2 and ZNF816A. Our study enriched the genetic basis and pathogenesis of psoriasis and highlighted the non-negligible impact of InDels on complex human diseases.

Morus alba L. (mulberry) twig is known to have an inhibitory effect on pathogens in traditional Chinese medicine. In the present study, the dermophytic fungus, Trichophyton rubrum , was used to evaluate the inhibitory effect of total M. alba twig extract and extracts obtained using solvents with different polarities by the method of 96‐well MTT colorimetry. The main active substance was isolated and identified by tracking its activity. In addition, the inhibitory effects of active extracts and a single active substance were investigated in combination with miconazole nitrate. Our data indicated that ethyl acetate extracts of mulberry twig (TEE) exhibited a desired inhibitory activity on T. rubrum with the minimum inhibitory concentration (MIC) of 1.000 mg/mL. With activity tracking, the main substance showing antimicrobial activity was oxyresveratrol (OXY), which was isolated from TEE. Its MIC for inhibiting the growth of T. rubrum was 0.500 mg/mL. The combined use of miconazole nitrate and OXY showed a synergistic inhibitory effect, as shown by a significant decrease in the MIC of both components. Based on the OXY content in TEE, the contribution rate of OXY to the inhibitory effect of TEE on T. rubrum was 80.52%, so it was determined to be the main antimicrobial substance in M. alba twig. Copyright © 2017 John Wiley & Sons, Ltd.

Rheumatoid arthritis (RA) is a systemic, chronic and inflammatory disease with unknown etiology [1]. Characteristic features of RA are chronic synovitis and a fluctuating clinical course, eventuall...

Trichothecene (TCN) contamination in food and feed is a serious challenge due to the negative health and economic impacts. Here, we confirmed that the glutathione S-transferase (GST) Fhb7-GST could broadly catalyze type A, type B and type D TCNs into glutathione epoxide adducts (TCN-13-GSHs). To evaluate the toxicity of TCN-13-GSH adducts, we performed cell proliferation assays in vitro, which demonstrated decreased cytotoxicity of the adducts. Moreover, in vivo assays (repeated-dose treatment in mice) confirmed that TCN-13-GSH adducts were dramatically less toxic than the corresponding TCNs. To establish whether TCN-13-GSH was metabolized back to free toxin during digestion, single-dose metabolic tests were performed in rats; DON-13-GSH was not hydrolyzed in vivo, but rather was quickly metabolized to another low-toxicity compound, DON-13-N-acetylcysteine. These results demonstrate the promise of Fhb7-GST as a candidate of detoxification enzyme potentially applied in TCN-contaminated agricultural samples, minimizing the detrimental effects of the mycotoxin.

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Abstract Background Symmetrical acral keratoderma ( SAK ) is a rare skin disorder and its pathogenesis and inheritability are unknown. Objectives To investigate the inheritance and pathogenesis of SAK . Methods Four SAK cases occurred in a four‐generation Chinese family. Exome sequencing identified SNP s with potential SAK ‐related mutations, and a potentially responsible gene transcription factor 4 ( TCF 4) was identified. TCF 4 was then sequenced in all 11 family members, and pedigree analysis was performed. Histopathology and immunohistochemistry evaluated TCF 4 expression in skin lesions. The gene mutation was investigated in human keratinocytes for keratin‐related protein expression. Results A novel heterozygous missense mutation, c.85C>A (p.Pro29Thr) was found in TCF 4. The mutation showed autosomal dominant inheritance and perfectly cosegregated with the SAK phenotype in all family members. In skin lesions, TCF 4 was present in the cytoplasm and membranes of the basal layer, the stratum spinosum and the stratum granulosum of the epidermis. The mutant TCF 4 induced overexpression of differentiation markers including KRT 1, KRT 14, loricrin and involucrin. Conclusions A SAK ‐related gene mutation in TCF 4 may function through transcriptional regulation of keratin.

Premature ovarian insufficiency (POI) is a group of heterogeneous disorders characterized by decreased ovarian reserve and increased follicle stimulating hormone (FSH) levels. It is rarely associated with short stature. FIGLA mutations with POI are identified with regard to heterozygosity; till date, only one affected family has been identified with homozygous mutations in FIGLA but without functional evaluation. Here, we described two POI patients from a consanguineous family from China. An 18-year-old girl and her sister presented with primary amenorrhea and increased FSH and luteinizing hormone levels, but the sister also presented with short stature and bone age delay. Whole-genome sequencing analysis identified a recurrent homozygous mutation in the FIGLA gene, c.2 T > C (p.Met1Thr), in this family member with POI; this variant was segregated within the pedigree. This change was absent in 382 control subjects, and we did not detect any mutations in 39 other idiopathic POI patients. in vitro functional analysis indicates that the p.Met1Thr mutation does not affect the transcription of the FIGLA gene, but blocks the synthesis of the full-length FIGLA protein. Our results support the notion that bi-allelic recessive loss-of-function effects of FIGLA contribute to POI patients with short stature and expand the FIGLA-related phenotypic spectrum.

Sugarcane mosaic virus (SCMV) frequently causes dramatic losses in maize production as the main pathogen of maize dwarf mosaic disease. It is important to understand the translational responses in maize to SCMV infection since viruses have to recruit host translation apparatus to express their proteins. However, due to technical limitations, research on virus translation lags far behind that on transcription. Here, we studied the relationship between systemic symptom expression and virus accumulation and found that both SCMV RNA and proteins accumulated rapidly during the systemic infection process in which varying degrees of chlorosis to mosaic symptoms developed on non-inoculated leaves. In addition, we applied ribosome profiling, which couples polysomal mRNA isolation with high-throughput sequencing, on the symptomatic leaves infected with SCMV to unravel the translational responses of maize to viral infection on a genome-wide scale. The results showed that only the genomic positive-stranded RNA of SCMV was involved in translation, and SCMV only occupied a small amount of translational resources of host plant at the early stage of infection. Further analyses on a global gene expression and gene ontology (GO) enrichment revealed that photosynthesis and metabolism were dramatically repressed at both transcriptional and translational levels. Altogether, our results laid a foundation for dissecting the molecular mechanism of plant translational responses to viral infection.

Structural variations (SVs; defined as DNA variants ≥ 50 base pairs) have been associated with various complex human diseases. However, research to screen the whole genome for SVs predisposing to psoriasis is lacking.To investigate the association of SVs and psoriasis.Using imputation, we performed a genome-wide screen of SVs on five independent cohorts with 45 386 participants from the Han Chinese population. Fine-mapping analysis, genetic interaction analysis and RNA expression analysis were conducted to explore the mechanism of SVs.In total, we obtained 4535 SVs and identified two novel deletions [esv3608550, odds ratio (OR) 2·73 (P < 2·00 × 10-308 ); esv3608542, OR 0·47 (P = 7·40 × 10-28 )] at 6q21·33 (major histocompatibility complex), one novel Alu element insertion [esv3607339; OR 1·22 (P = 1·18 × 10-35 )] at 5q33·3 (IL12B) and confirmed one previously reported deletion [esv3587563; OR 1·30 (P = 9·52 × 10-60 )] at 1q21·2 (late cornified envelope) for psoriasis. Fine-mapping analysis including single-nucleotide polymorphisms (SNPs) and small insertions/deletions revealed that esv3608550 and esv3608542 were independently associated with psoriasis, and a novel independent SNP [rs9378188; OR, 1·65 (P = 3·46 × 10-38 )] was identified at 6q21·33. By genetic interaction analysis and RNA expression analysis, we speculate that the association of two deletions at 6q21·33 with psoriasis might relate to their influence on the expression of HLA-C.We have constructed the most comprehensive SV map for psoriasis thus far and enriched the genetic architecture and pathogenesis of psoriasis, and highlight the non-negligible impact of SVs on complex diseases.

Recent studies confirmed that the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) can regulate the proliferation and migration of tumour cells.1-4 Lung adenocarcinoma (LUAD) is the subtype with the largest proportion of lung cancer.5, 6 Huang et al. confirmed that GABA content in LUAD tissues was obviously higher than normal tissues by collecting clinical tissues.7 By analysing GABA expression in different LUAD patients, we established a GABA-driven LUAD classification and developed a GABA-driven prognostic signature. We demonstrated that GABA can be used as a biomarker for prognostic assessment and individualised treatment of LUAD. We first established a GABA-driven LUAD classification using conventional genetic databases and clustering algorithms. By performing an overall search of GABA-related pathways from the Molecular Signatures Database (MSigDB),8 we acquired 221 GABA-related genes from 15 gene sets, including Gene Ontology (GO), Human Phenotype Ontology (HPO), WikiPathways, Biocarta, Reactome and many other diverse biological functions and sources. After difference analysis of these genes in tumour and normal tissue by ‘limma’ package, 108 GABA core difference genes were obtained according to the absolute value of logFC > .5 (Table S1). Based on 108 GABA core differential genes, consensus clustering was performed in The Cancer Genome Atlas (TCGA)-LUAD queue (n = 555) by using the ‘ConsensusClusterPlus’ package. K value of 4 was selected by the delta area plot, then we classified LUAD patients into four subtypes (Figure 1A and B). We further explored the expression of GABA core genes in four subtypes (Figure S1). The key genes for GABA include the synthetic rate-limiting enzymes glutamic acid decarboxylase1 (GAD1) and GAD2 and the receptors GABAA and GABAB. Kaplan–Meier analysis of four subtypes showed that cluster 1 had the best prognosis (Figure 1C) (p < .0001). And cluster 2 patients showed a significantly worse prognosis compared with non-cluster 2 patients (Figure S2A-D) (p < .0001). Differential analysis was conducted in the TCGA cohort using the ‘limma’ package, and 500 characteristic genes for each subtype were obtained, with a total of 2000 (Table S2). Based on the characteristic genes of four subtypes, the samples were classified in three Gene Expression Omnibus (GEO) queues (GSE31210, GSE41271, GSE72094) using Nearest Template Prediction (NTP) algorithm.9 We then confirmed the accuracy and stability of our TCGA-LUAD classification by performing a survival analysis on the three GEO cohorts (Figure 1D-F) and comparing the similarity between the training set TCGA and the three GEO validation sets using the SubMap algorithm (Figure 1G-I). We selected the gene that contributed most to the prognosis of cluster 2, EZH2, and detected its expression in LUAD tissues. The results of immunohistochemistry (IHC) showed that EZH2 expression was increased in LUAD tissues of patients with poor prognosis (Figure 1J), which was consistent with our analysis results and further proved the accuracy of our LUAD classification based on the core differential genes. In order to study the potential biological functions of different subtypes, 9570 gene set pathways were collected from the MSigDB database, including 50 cancer hallmark gene sets, 186 Kyoto Encyclopedia of Genes and Genomes (KEGG) gene sets, 196 Pathway Interaction Database (PID) gene sets, 289 Biocarta gene sets, 1499 Reactome gene sets, and 7350 GO biological process gene sets. Function enrichment analysis was then conducted by using the ‘clusterProfiler’ R package. The results showed that cluster 1 was mainly enriched in pathways such as ‘immune response’, ‘T cells’ and ‘leukocyte’ (Figure S3A), which related to immunotherapy. The functions of the remaining subtypes are mainly concentrated in pathways related to cell proliferation, differentiation or energy metabolism (Figure S3B-D). Considering the importance of immunotherapy in LUAD, we evaluated the immune landscape of each subtype. First, the degree of infiltration of some tumour immune cells in TCGA-LUAD queue was assessed by the single-sample gene set enrichment analysis (ssGSEA) algorithm. As shown in the thermal and box diagrams (Figure 2A), the immune cell infiltration of cluster 1 was obvious, covering CD8+T cells and B cells. Next, we evaluated the expression of each immune checkpoint in four subtypes (Figure 2B). It can be clearly observed that the expression of various immune checkpoints in cluster 1 were obviously higher than that in other subtypes, such as cytotoxic T lymphocyte antigen 4 (CTLA4). To further understand the immunotherapy status of various subtypes, tumour inflammation signature (TIS), antigen presentation score (APS), tumour immune dysfunction and exclusion (TIDE) methods were applied to evaluate the effectiveness of different subtypes to immunotherapy. As expected, cluster 1 showed higher scores in the three indicators (Figure 2C-F) (TIS p = 4.9e-06; APS p = 2.4e-06; TIDE p = 6e-06), indicating that patients in cluster 1 could gain greater efficacy in immunotherapy. We used the SubMap algorithm to verify the similarity of expression between TCGA and three immunotherapy queues (GSE78220 (n = 28), GSE91061 (n = 109) and IMvigor210 (n = 348)). The results showed that cluster 1 predicted better immune response in the three queues (Figure S4A-C). We also screened specific drugs for each subtype and evaluated the sensitivity of each subtype to star drugs. As shown in Figure 3A, AS-703026 obtained from PRISM database can be considered as a specific drug for cluster 1. The specific drugs from the Cancer Therapeutics Response Portal (CTRP) and PRISM databases of cluster 2 are shown in Figure 3B, and the specific drugs of cluster 3 are shown in Figure 3C and Table S3. Then we screened out the area under the curve (AUC) of each subtype against several star drugs; the results are shown in Figure 3D-H. For example, Cluster 1 was more sensitive to osimertinib and sorafenib. We further constructed a GABA-driven LUAD prognostic signature (GDLPS) based on the above 108 GABA differential genes. Our GDLPS divided LUAD into high- and low-risk group. High-risk group predicted worse survival outcomes (Figure 4A) (p < .0001). Then the GDLPS was verified in three GEO cohorts (GSE31210, GSE41271 and GSE72094), and the results were same as the above results (Figure S5A-C) (all p < .002). We further explored the immune landscape of patients in two groups. Our results displayed that the immune cells infiltration and the immune checkpoints expression of the low-risk group were higher (Figure 4B and C). The TIS and APS results (Figure 4D and E) showed that the immunotherapy benefits of low-risk group were higher (p = .0059, p = 7.2e-10). Meanwhile, the immunotherapeutic potential of patients was evaluated in three GEO validation queues (Figure S5D-F), which verified the above calculation results (GSE35640, p = .028; GSE91061, p = .0027; GSE100797, p = .045). Finally, we combined some traditional clinical indicators such as age and stage to build a nomogram (Figure 4F). The sum of the scores obtained from the three indicators is the total score of the patients, which is used to predict the survival probability. The receiver operating characteristic (ROC) curve and calibration plot showed that our nomograph has high accuracy and stability (Figure S5G-H). In conclusion, based on the differential expression of GABA in LUAD patients, we classified LUAD patients and comprehensively considered the clinical significance of the classification. We found that differential expression of GABA predicts different prognosis of LUAD. Our study indicated that the different expression of GABA is closely related to immune cell infiltration, immune checkpoint expression and sensitivity to chemotherapy drugs in LUAD patients. We also developed a GABA-driven prognosis signature for LUAD. Overall, our research indicated that GABA may be an excellent biomarker for evaluating the classification, treatment and prognostic evaluation of patients with LUAD. The authors declare no potential conflicts of interest. The Collaborative Innovation Major Project of Zhengzhou (Grant No. 20XTZX08017), the National Natural Science Foundation of China (Grant No. 82002433), Science and Technology Project of Henan Provincial Department of Education (Grant No. 21A320036), Young and Middle-aged Health Science and Technology Innovation Talents in 2020(Grant No. YXKC2020049), Henan Province Medical Science and Technology Research Project Joint Construction Project (Grant No. LHGJ20190003, LHGJ20190055). All datasets generated for this study are included in the article/Supplementary Material. Figure S1. The expression of GABA core genes in each subtype. GABA-related genes were significantly overexpressed in cluster 1. However, the expression of these genes was generally lower in cluster 3. Figure S2. Comparison of OS between cluster 2 and non-cluster 2 (A) Comparison of OS between cluster 2 and non-cluster 2 in TCGA. (B-D) OS of cluster 2 and non-cluster 2 in the three GSE cohorts. Figure S3. Functional enrichment of each subtype. (A-D) Enrichment score of four clusters. Figure S4. SubMap analysis of each cluster in three verification cohorts. Figure S5. (A-C) OS of two risk groups in three GEO verification queues. (D-F) Immune response of two groups of patients in three validation queues. (G, H) The ROC curve and calibration plot of nomograph. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Spleen tyrosine kinase (SYK) is a non-receptor tyrosine kinase. The dysregulation of SYK is closely related to the occurrence and development of allergic diseases, autoimmune diseases and cancer. SYK has become an attractive target for drug discovery due to its important biological functions. This article reviews the biological function of SYK, the relationship between SYK and disease, and therapies targeting SYK. In addition, inspired by new technologies such as proteolysis targeting chimeras (PROTACs) and phosphatase recruiting chimeras (PHORCs), we propose the development of new therapeutic approaches for targeting SYK, such as SYK PROTACs and SYK PHORCs, which may overcome deficiencies of existing methods.

Nonalcoholic fatty liver disease (NAFLD) has been reported to have effects on kidney diseases; however, a link between NAFLD and urinary calculi remains to be confirmed. This study was conducted on a male population based on our previous Fangchenggang Area Male Health and Examination Survey in Guangxi, China in order to estimate the frequency of urinary calculi and assess the association between NAFLD and urinary calculi while controlling for possible confounders.This was a population-based cross-sectional study conducted in the Fangchenggang region in Guangxi, China. The diagnoses of NAFLD and urinary calculi were made by ultrasonography. Clinical and laboratory findings were analyzed to investigate whether NAFLD was a risk factor for urinary calculi.A total of 3719 men were enrolled (age range, 17 to 88 years). Slightly more than a quarter (26.5%) of the participants were diagnosed with NAFLD. The percentage of urinary calculi in all participants was 6.9%, and the percentage of NAFLD patients with urinary calculi (8.4%) was significantly higher than that among patients without NAFLD (6.4%, P < .05). Advanced age; high body mass index; elevated levels of blood glucose, cholesterol, triglycerides, and low-density lipoprotein cholesterol; low education; lower or higher physical activity; and NAFLD were independent risk factors for urinary calculi (P < .05).Our results showed that NAFLD was associated with a higher incidence of urinary calculi in this cohort and NAFLD might represent a risk factor for urinary calculi.

Abstract Tomato ( S olanum lycopersicum L.) is one of the most important vegetable crops in the world. However, the tomato production is severely affected by many diseases. The use of host resistance is believed to be the most effective approach to control the pathogens. In this study, a total of 1003 resistance‐like genes were identified from the tomato genome using individual full‐length search and conserved domain verification approach. Of the predicted resistance genes, serine/threonine protein kinase was the largest class with 384 genes followed by 212 genes encoding receptor‐like kinase, 107 genes encoding receptor‐like proteins, 68 genes encoding coiled‐coil–nucleotide‐binding site ( NBS )–leucine‐rich repeat ( LRR ) and 19 genes encoding Toll interleukin‐1 receptor domain‐ NBS ‐ LRR . Physical map positions established for all predicted genes using the tomato WGS chromosomes SL 2.40 information indicated that most resistance‐like genes clustered on certain chromosomal regions. Comparisons of the sequences from the same resistance‐like genes in S . pimpinellifolium and S . lycopersicum showed that 93.5% genes contained single nucleotide polymorphisms and 19.7% genes contained insertion/deletion. The data obtained here will facilitate isolation and characterization of new resistance genes as well as marker‐assisted selection for disease resistance breeding in tomato.

To explore the correlation between platelet endothelial aggregation receptor-1 (PEAR1) genetic polymorphism and pulmonary thromboembolism (PTE). Variant loci of the PEAR1 gene were screened in a PTE pedigree, followed by verification using Sanger sequencing. These polymorphic loci were validated in 101 PTE patients and 132 matched normal patients using MassARRAY single nucleotide polymorphism (SNP) genotyping methods. The frequency differences between the allele and genotypes were compared using the Hardy–Weinberg equilibrium test and Chi-square test. The correlation between the PEAR1 gene SNP and PTE was analyzed by comparing the between-group variance differences using the χ2 test. Three SNPs were identified in the PTE pedigree. There was a heterozygous transition of T>C in rs1952294, and a transition of C>T in rs778026543 in 2 members in the pedigree; however, the rs778026543 was not identified in the 101 PTE patients and 132 healthy controls. The genotype and allele frequencies of rs822442 did not differ significantly between PTE patients and healthy controls (P > 0.05). The variance difference at rs778026543 between pedigree members and healthy controls was significant (P < 0.001), supporting its potential heredity. The PEAR1 polymorphism, rs778026543, but not rs1952294 and rs822442, may be a susceptibility SNP for PTE.

Tobacco use is one of the leading causes of preventable disease worldwide. Genetic studies have elucidated numerous smoking-associated risk loci in American and European populations. However, genetic determinants for cigarette smoking in Chinese populations are under investigated. In this study, a whole-genome sequencing (WGS)-based genome-wide association study (GWAS) was performed in a Chinese Han population comprising 620 smokers and 564 nonsmokers. 13 single-nucleotide polymorphisms (SNPs) of the Raftlin lipid linker 1 (RFTN1) gene achieved genome-wide significance levels (P &lt; 5 x 10-8) for smoking initiation. The rs139753473 from RFTN1 and six other suggestively significant loci from CUB and Sushi Multiple Domains 1 (CSMD1) gene were also associated with cigarettes per day (CPD) in an independent Chinese sample consisting of 1329 subjects (805 smokers and 524 nonsmokers). When treating males separately, associations between smoking initiation and PCAT5/ANKRD30A, two genes involved in cancer development, were identified and replicated. Within RFTN1, two haplotypes (i.e., C-A-C-G and A-G-T-C) formed by rs796812630-rs796584733-rs796349027-rs879511366 and three haplotypes (i.e., T-T-C-C-C, T-T-A-T-T and C-A-A-T-T) formed by rs879401109-rs879453873-rs75180423-rs541378415-rs796757175 were strongly associated with smoking initiation. In addition, we also revealed two haplotypes (i.e., C-A-G-G and T-C-T-T derived from rs4875371-rs4875372-rs17070935-rs11991366) in CSMD1 gene showing significant association with smoking initiation. Further bioinformatics functional assessment suggests that RFTN1 might participate in smoking behavior through modulating immune responses or interactions with the glucocorticoid receptor alpha and the androgen receptor. Together, our results may help understand the mechanisms underlying smoking behavior in the Chinese Han population.

Abstract Background The speciation and fast global domestication of bread wheat have made a great impact on three subgenomes of bread wheat. DNA base composition is an essential genome feature, which follows the individual-strand base equality rule and [AT]-increase pattern at the genome, chromosome, and polymorphic site levels among thousands of species. Systematic analyses on base compositions of bread wheat and its wild progenitors could facilitate further understanding of the evolutionary pattern of genome/subgenome-wide base composition of allopolyploid species and its potential causes. Results Genome/subgenome-wide base-composition patterns were investigated by using the data of polymorphic site in 93 accessions from worldwide populations of bread wheat, its diploid and tetraploid progenitors, and their corresponding reference genome sequences. Individual-strand base equality rule and [AT]-increase pattern remain in recently formed hexaploid species bread wheat at the genome, subgenome, chromosome, and polymorphic site levels. However, D subgenome showed the fastest [AT]-increase across polymorphic site from Aegilops tauschii to bread wheat than that on A and B subgenomes from wild emmer to bread wheat. The fastest [AT]-increase could be detected almost all chromosome windows on D subgenome, suggesting different mechanisms between D and other two subgenomes. Interestingly, the [AT]-increase is mainly contributed by intergenic regions at non-selective sweeps, especially the fastest [AT]-increase of D subgenome. Further transition frequency and sequence context analysis indicated that three subgenomes shared same mutation type, but D subgenome owns the highest mutation rate on high-frequency mutation type. The highest mutation rate on D subgenome was further confirmed by using a bread-wheat-private SNP set. The exploration of loci/genes related to the [AT] value of D subgenome suggests the fastest [AT]-increase of D subgenome could be involved in DNA repair systems distributed on three subgenomes of bread wheat. Conclusions The highest mutation rate is detected on D subgenome of bread wheat during domestication after allopolyploidization, leading to the fastest [AT]-increase pattern of D subgenome. The phenomenon may come from the joint action of multiple repair systems inherited from its wild progenitors.

This study was designed to determine the differential profiles of long non-coding RNAs (lncRNAs) between rheumatoid arthritis (RA) and gouty arthritis (GA), which may lead to the discovery of specific biomarkers for RA diagnosis and treatment in the future.The profiles of lncRNAs were determined by Agilent microarray. Bioinformatics analyses, including Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, of the large dataset obtained from microarray experiments were performed.A total of 765 lncRNAs and 2,808 mRNAs were significantly and differentially expressed in RA samples as compared to GA samples. Moreover, of 2,808 differentially expressed mRNAs, 178 upregulated mRNAs and 21 downregulated mRNAs were identified to be strongly correlated with lncRNAs examined in this study. Bioinformatics analyses revealed the tumor-like phenotype of synovial cells in RA and the involvement of immune system process in GA. In addition, this study demonstrated the significantly different molecular origins of two Chinese Medicine syndrome patterns of RA patients -- blood stasis and non-blood stasis.Our study showed for the first time the differentially expressed lncRNA profiles in synovial tissues between RA and GA and between two clinical phenotypes of RA patients differentiated by Chinese Medicine. This study helps achieving personalized medicine in RA. Larger-scale studies are required to validate the data presented.

Acne is a common chronic inflammatory skin disease, and the inflammation immune response runs through all stages of acne lesions. In this study, we use a combination of multiplex-PCR and high-throughput sequencing technologies to analyze T cell receptor β chain CDR3 (complementarity-determining region 3) in peripheral blood isolated from severe acne patients. Once compared with healthy controls, we propose to identify acne-relevant CDR3 peptides. Our results reveal that the diversity of T cell receptor β chain (TRB) CDR3 sequences in the peripheral blood of the severe acne vulgaris (SA) group differed from that of the control group. In addition, we find 10 TRB CDR3 sequences, amino acid sequences and V-J combinations with significantly different expressions between the SA group and the non-acne (NA) group (P < 0.0001). These findings may contribute to a better understanding of the role of immunity in the pathogenesis of acne and may serve as biomarkers for evaluating risk or prognosis of severe acne disease in future.

Abstract Background Hydrogen sulfide (H 2 S) is the most important compound causing oral malodor, and its concentration is thought to be closely correlated with oral microorganism activity. Therefore, clarifying the correlation between oral microbes and metabolites is important. Methods This study tested with 16S rRNA gene amplicon and shotgun metagenomic sequencing of oral microorganisms and oral malodor tests. Results There were different of the microbial taxa between the low and high H 2 S groups. And in the high H 2 S group, most of the enriched taxa were genera which abundance was correlated with H 2 S concentration. Fusobacterium periodonticum and Prevotella nanceiensis were significantly different in coverage breadth and depth and in LPS biosynthesis contributions between the two groups. The contribution of F . periodonticum to sulfur metabolism was significantly different between the two groups, and the relative F . periodonticum abundance was higher in the high H 2 S group. Conclusions The H 2 S content is significantly associated with the oral cavity microorganism composition and abundance. Most microorganisms enriched in people with high H 2 S levels are associated with oral diseases such as caries and periodontal diseases.

Journal of the European Academy of Dermatology and VenereologyVolume 31, Issue 11 p. e510-e512 Letter to the Editor A novel non-frameshift deletion in MVK gene responsible for disseminated superficial actinic porokeratosis in one Chinese family C.-X. Li, C.-X. Li Department of Dermatology, Dongguan Sixth People's Hospital, Dongguan, Guangdong, ChinaAuthors Chang-Xing Li, Si-Long Sun and Jing-Yao Liang contributed equally to this work.Search for more papers by this authorS.-L. Sun, S.-L. Sun Department of Dermatology, Dongguan Sixth People's Hospital, Dongguan, Guangdong, ChinaAuthors Chang-Xing Li, Si-Long Sun and Jing-Yao Liang contributed equally to this work.Search for more papers by this authorJ.-Y. Liang, J.-Y. Liang Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, Guangdong, ChinaAuthors Chang-Xing Li, Si-Long Sun and Jing-Yao Liang contributed equally to this work.Search for more papers by this authorY.-Q. Yuan, Y.-Q. Yuan Department of Dermatology, Dongguan Sixth People's Hospital, Dongguan, Guangdong, ChinaSearch for more papers by this authorS.-Q. Zhang, S.-Q. Zhang Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, Guangdong, ChinaSearch for more papers by this authorP.-J. Chen, P.-J. Chen Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaSearch for more papers by this authorK. Zeng, Corresponding Author K. Zeng npfkzk@163.com Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaCorrespondence: X.-B. Zhang and K. Zeng. E-mails: zxibao@126.com and npfkzk@163.comSearch for more papers by this authorX.-F. Xie, X.-F. Xie Department of Dermatology, Dongguan Sixth People's Hospital, Dongguan, Guangdong, ChinaSearch for more papers by this authorX.-B. Zhang, Corresponding Author X.-B. Zhang zxibao@126.com Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, Guangdong, ChinaCorrespondence: X.-B. Zhang and K. Zeng. E-mails: zxibao@126.com and npfkzk@163.comSearch for more papers by this author C.-X. Li, C.-X. Li Department of Dermatology, Dongguan Sixth People's Hospital, Dongguan, Guangdong, ChinaAuthors Chang-Xing Li, Si-Long Sun and Jing-Yao Liang contributed equally to this work.Search for more papers by this authorS.-L. Sun, S.-L. Sun Department of Dermatology, Dongguan Sixth People's Hospital, Dongguan, Guangdong, ChinaAuthors Chang-Xing Li, Si-Long Sun and Jing-Yao Liang contributed equally to this work.Search for more papers by this authorJ.-Y. Liang, J.-Y. Liang Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, Guangdong, ChinaAuthors Chang-Xing Li, Si-Long Sun and Jing-Yao Liang contributed equally to this work.Search for more papers by this authorY.-Q. Yuan, Y.-Q. Yuan Department of Dermatology, Dongguan Sixth People's Hospital, Dongguan, Guangdong, ChinaSearch for more papers by this authorS.-Q. Zhang, S.-Q. Zhang Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, Guangdong, ChinaSearch for more papers by this authorP.-J. Chen, P.-J. Chen Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaSearch for more papers by this authorK. Zeng, Corresponding Author K. Zeng npfkzk@163.com Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, ChinaCorrespondence: X.-B. Zhang and K. Zeng. E-mails: zxibao@126.com and npfkzk@163.comSearch for more papers by this authorX.-F. Xie, X.-F. Xie Department of Dermatology, Dongguan Sixth People's Hospital, Dongguan, Guangdong, ChinaSearch for more papers by this authorX.-B. Zhang, Corresponding Author X.-B. Zhang zxibao@126.com Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, Guangdong, ChinaCorrespondence: X.-B. Zhang and K. Zeng. E-mails: zxibao@126.com and npfkzk@163.comSearch for more papers by this author First published: 23 May 2017 https://doi.org/10.1111/jdv.14360Citations: 3 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume31, Issue11November 2017Pages e510-e512 RelatedInformation

ABSTRACT Emerging evidence has indicated an association between the gut microbiome and arthritis diseases including gout. This metagenomic study aims to investigate the possible role of gut microbiota in the development of gout. The results exhibit gout patients have higher abundance of Prevotella, Fusobacterium spp. and Bacteroides spp., whereas healthy controls have higher abundance of Enterobacteriaceae spp., butyrate-producing species, including Roseburia spp., Butyrivibrio spp. and Coprococcus spp. and anti-inflammatory Faecalibacterium prausnitzii . Functional analysis shows gut microbiome of gout patients have higher potential for fructose, mannose metabolism and lipid A biosynthesis, but lower potential for urate degradation and SCFAs production. Enterobacteriaceae spp. may contribute to urate degradation and provide immunostimulatory effect in healthy controls. A disease classifier based on gut microbiota shows positive performance in the discovery and validation cohorts (93.03% and 89.13% accuracy, respectively). The effect of uric-acid-lowering and anti-inflammatory drugs on the gut microbiome is mild. Integrative analyses of four additional diseases (obesity, type 2 diabetes, ankylosing spondylitis and rheumatoid arthritis) indicates gout seems to be more similar to autoimmune diseases than metabolic diseases. This work demonstrates an altered gut microbiota might influence the development of gout and provides new insights into the diagnosis and treatment of the disease.

Prolamins, unique to Gramineae (grasses), play a key role in the human diet. Thinopyrum elongatum (syn. Agropyron elongatum or Lophopyrum elongatum), a grass of the Triticeae family with a diploid E genome (2n = 2x = 14), is genetically well-characterized, but little is known about its prolamin genes and the relationships with homologous loci in the Triticeae species.In this study, a total of 19 α-gliadin, 9 γ-gliadin, 19 ω-gliadin, 2 high-molecular-weight glutenin subunit (HMW-GS), and 5 low-molecular-weight glutenin subunit (LMW-GS) genes were identified in the Th. elongatum genome. Micro-synteny and phylogenetic analysis revealed dynamic changes of prolamin gene regions and genetic affinities among Th. elongatum, Triticum aestivum, T. urartu and Aegilops tauschii. The Th. elongatum genome, like the B subgenome of T. aestivum, only contained celiac disease epitope DQ8-glia-α1/DQ8.5-glia-α1, which provided a theoretical basis for the low gluten toxicity wheat breeding. The transcriptome data of Th. elongatum exhibited differential expression in quantity and pattern in the same subfamily or different subfamilies. Dough rheological properties of T. aestivum-Th. elongatum disomic substitution (DS) line 1E(1D) showed higher peak height values than that of their parents, and DS6E(6D) exhibited fewer α-gliadins, which indicates the potential usage for wheat quality breeding.Overall, this study provided a comprehensive overview of the prolamin gene family in Th. elongatum, and suggested a promising use of this species in the generation of improved wheat breeds intended for the human diet.

Due to their benefits in interior thermal comfort, energy saving, and noise reduction, radiant cooling systems have received wide attention. Radiant cooling systems can be viewed as a part of buildings’ maintenance structure and a component of cooling systems, depending on their construction. This article reviews studies on heat exchange in rooms utilizing radiant cooling systems, including research on conduction in radiant system structures, system cooling loads, cooling capacity, heat transfer coefficients of cooling surfaces, buildings’ thermal performance, and radiant system control strategy, with the goal of maximizing the benefits of energy conservation. Few studies have examined how radiant cooling systems interact with the indoor environment; instead, earlier research has focused on the thermal performance of radiant cooling systems themselves. Although several investigations have noted variations between the operating dynamics of radiant systems and conventional air conditioning systems, the cause has not yet been identified and quantified. According to heat transfer theory, the authors suggest that additional research on the performance of radiant systems should consider the thermal properties of inactive surfaces and that buildings’ thermal inertia should be used to coordinate radiant system operation.

Abstract Background Epidermolytic palmoplantar keratoderma (EPPK) is a rare skin disorder and its pathogenesis and inheritability are unknown. Objective To investigate the inheritance and pathogenesis of EPPK. Methods Two EPPK cases occurred in a three‐generation Chinese family. Patient–parents trio EPPK was carried out and the identified candidate variants were confirmed by Sanger sequencing. Results A heterozygous missense pathogenic variant, c.488G &gt; A (p.Arg163Gln), in the keratin ( KRT ) 9 gene was detected in the proband and his son via targeted exome sequencing, and then validated by Sanger sequencing. This pathogenic variant cosegregated with the EPPK in extended family members, and was predicted to be pathogenic by SIFT, PolyPhen2, PROVEAN, and Mutation Taster. This heterozygous variation was not evident in 100 healthy controls. Conclusion This report describes a KRT9 c.488G &gt; A (p.Arg163Gln) variant causing a diffuse phenotype of Chinese EPPK. The current results broaden the spectrum of KRT9 pathogenic variants responsible for EPPK and have important implications for molecular diagnosis, treatment, and genetic counseling for this family.

Plant epidermis serves important functions in shoot growth, plant defense and lipid metabolism, though mechanisms of related transcriptional regulation are largely unknown. Here, we identified cis-elements specific to shoot epidermis expression by dissecting the promoter of Triticum aestivum lipid transfer protein 1 (TaLTP1). A preliminary promoter deletion analysis revealed that a truncated fragment within 400 bp upstream from the translation start site was sufficient to confer conserved epidermis-specific expression in transgenic Brachypodium distachyon and Arabidopsis thaliana. Further, deletion or mutation of a GC(N4)GGCC motif at position -380 bp caused a loss of expression in pavement cells. With an electrophoretic mobility shift assay (EMSA) and transgenic reporter assay, we found that a light-responsive CcATC motif at position -268 bp was also involved in regulating pavement cell-specific expression that is evolutionary conserved. Moreover, expression specific to leaf trichome cells was found to be independently regulated by a CCaacAt motif at position -303 bp.

To the Editor: Neisseria gonorrhoeae (NG) with decreased susceptibility to ceftriaxone (CRO) and cefixime, the last option for first-line anti-microbial monotherapy, was spread globally. Until now, more than ten clinical treatment failures with CRO have been reported with minimum inhibitory concentration (MIC) range as 0.5 to 2.0 mg/L.[1] CRO, thereafter, is no longer recommended as monotherapy for gonorrhea. Instead, dual therapy that combines CRO with azithromycin is currently exerted in many countries including China. However, the first treatment failure to dual therapy (500 mg CRO plus 1 g azithromycin) was identified in 2014 in London.[1] The reasons for NG to gain the resistance to anti-microbial agents are either through spontaneous mutation and/or horizontal genetic transfer. Here, we applied whole-genome sequencing (WGS) to compare the mutation accumulation between NG isolates with susceptibility to CRO (CRO-S, MIC < 0.125 mg/L) and that with decreased susceptibility to CRO (CRO-DS, MIC ≥ 0.25 mg/L). NG isolates were collected from patients at the sexually transmitted infection clinics in Guangzhou, China, 2009 to 2013. Anti-microbial susceptibility was determined using the agar dilution method as previously described. Twenty-two CRO-DS NG isolates and 22 CRO-S NG isolates were included, which the selected isolates between the two groups were, respectively, matched as closely as possible by comparing their MICs for ciprofloxacin, spectinomycin, and azithromycin [Supplementary Table 1, https://links.lww.com/CM9/A238]. WGS was performed using Illumina HiSeq 4000 platform (Illumina, San Diego, CA, USA). The high-quality reads were aligned onto the publically available reference genome (NG NCCP11945, NC_011035) with Burrows-Wheeler Aligner version 0.5.9-r16, and then single-nucleotide variants are identified using Sequence Alignment Map tools (version 0.1.19-44428cd). The gene mutations attributed to CRO-DS such as mtrR promoter 23 to 35 A deletion, mtrR Gly45, penA Ala501, penA GLy542 and penA Pro551, porB1b Gly120, and porB1b Ala121 were identified from the WGS data. A neighbor-joining phylogenetic tree of single-nucleotide variants was generated by MEGAN7. After filtering low-quality bases and adapter sequences, the abundance of clean WGS reads shows no difference between CRO-S and CRO-DS NG (P > 0.05) [Figure 1A]. The point mutations in CRO-S NG strain as shown in Figure 1B are significantly more than that in CRO-DS NG isolates, illustrating by total (6206.46 ± 776.50 vs. 5420.73 ± 770.68, P < 0.01), homozygous (5694.32 ± 766.86 vs. 4968.59 ± 738.41, P < 0.01), and heterozygous mutation (512.14 ± 61.27 vs. 452.14 ± 69.85, P < 0.01), respectively. Moreover, a significant negative correlation was found between CRO MICs (range 0.004–0.500 mg/L) and the total number of point mutations (r = −0.4737, P = 0.0012), homozygous point mutations (r = −0.4631, P = 0.0015), or heterozygous point mutations (r = −0.3348, P = 0.0263) [Figure 1C]. The point mutation types such as A > G, G > A, C > T, and T > C have high frequency in homozygous mutations as well as in heterozygous mutations; moreover, such types are significantly higher in CRO-S NG when compared with CRO-DS NG [Figure 1D]. The difference of point mutations between CRO-S and CRO-DS was also analyzed using circos plots [Figure 1E], which showed similar findings that CRO-S NG possessed more mutations than CRO-DS NG. In contrast, the point mutations within mtrR promoter 23 to 35 A deletion, at loci of penA (Ala501, GLy542, or Pro551) and porB1b (Gly120 or Ala121) with the exception of mtrR Gly45, were slightly lower in CRO-S NG than that in CRO-DS NG, although the difference was not statistically significant [Figure 1F and Supplementary Figure 1, https://links.lww.com/CM9/A239].Figure 1: Differences of point mutations between CRO-S NG (n = 22) and CRO-DS NG (n = 22). (A) The amount of clean whole genome sequencing data is not different in CRO-S and CRO-DS NG isolates group. (B) The number of point mutations (total, homozygous, and heterozygous) in CRO-S NG and CRO-DS NG. (C) The point mutations (total, homozygous, and heterozygous) are negatively correlated with CRO MICs, respectively. (D) The overall mutation types are shared or different between CRO-S and CRO-DS NG isolates. (E) The circos diagram summarizes the point mutations in NG genome. The tracks from outer to inner rings represent NG genome (in Mb), the point mutations in CRO-S NG, the point mutations in CRO-S NG minus that in CRO-DS NG (green represents more mutations in CRO-S NG, whereas red represents more mutations in CRO-DS NG), the point mutations in CRO-DS NG, A > G plot (green represents in CRO-S NG, red represents in CRO-S NG), G > A plot, C > T plot, and T > C plot. (F) Phylogeny of NG based on single nucleotide variants, with the tracks from outer to inner rings representing amino acid mutations at mtrR promoter 23–35 A deletion, mtrR Gly45, penA Ala501, penA GLy542, penA Pro551, porB1b Gly120, and porB1b Ala121. ∗P < 0.05 and ∗∗P < 0.01, as CRO-S NG compared to CRO-DS NG. CRO: Ceftriaxone; MIC: Minimum inhibitory concentration; NG: Neisseria gonorrhoeae.Interestingly, this study provides evidence that CRO-S NG has markedly more point mutations (homozygous and/or heterozygous) compared with CRO-DS NG. CRO-S NG evolving under certain selection may be required to acquire more mutations for conferring resistance, whereas CRO-DS NG may only need relatively lower mutations because it has acquired some degree of resistance evolution to cope with such selection; however, further studies are needed to clarify this hypothesis. Indeed in present study, several mutations such as mtrR promoter 23 to 35 A deletion, penA (Ala501, GLy542, or Pro551), and porB1b (Gly120 or Ala121), correlated well with CRO-DS, were more frequently observed in CRO-DS NG, although these mutations were also presented in CRO-S NG. A previous study has strongly suggested a positive relationship between hypermutable (mutator) bacteria and acquisition of antibiotic resistance.[2] Wistrand-Yuen et al[3] recently reported that the bacteria evolved high-level resistance in response to lethal selection are different from those in sub-MIC selection; only few strong-effect resistance mutations are observed during lethal selections and sub-MIC selection generates many small-effect resistance mutations, but combination of such small-effect mutations can cause high-level resistance as well. Therefore, due to its hyper-mutation and the potential occurrence of resistance mutations, molecular surveillance of CRO-S NG should be enhanced as well as CRO-DS NG in the future. Funding This study was supported by grants from the Natural Science Foundation of Guangdong (No. 2018A0303130011), the Medical and Health Technology Projects of Guangzhou (No. 20171A011284), and the Medical Science and Technology Research Foundation of Guangdong Province (No. A2017239). Conflicts of interest None.

Abstract BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous psychiatric disorder that can be divided into inattentive (I-ADHD), hyperactive-impulsive (HI-ADHD), and combined (C-ADHD) subtypes. Different early life events and environmental factors correlated with the gut microbiota community have been implicated in the development of ADHD. However, whether different ADHD symptomatic presentations are associated with distinct microbiota composition and function still unknown. Therefore, we carried out metagenomic analysis from 207 subjects to characterize the gut microbial profiles in ADHD and subgroup patients.ResultsThe current study revealed that the gut microbiota composition (beta diversity) can be effectively distinguished between C-ADHD patients and HCs, but not I-ADHD patients and HCs, nor general ADHD patients and HCs. Features include underrepresentation of 8 species belonging to the genus Bacteroides and enrichment of 5 species of Bifidobacterium and Prevotella in general ADHD patients (all p &lt; 0.05). Eight of the above species became progressively reduced ( ovatus , thetaiotaomicron , intestinalis , cellulosilyticus , and fluxus belonging to the genus Bacteroides ) or enriched ( Prevotella_copri , Prevotella_buccae and Bifidobacterium_breve ) from healthy controls (HCs) to I-ADHD and C-ADHD patients. Predicted metabolic functions from these distinguished gut microbial markers described a certain compensatory host metabolism in ADHD and subgroup patients. Particularly, pyridoxal 5'-phosphate (a dominant vitamin B6 active type) biosynthesis pathways were significantly reduced in C-ADHD patients, because serum vitamin B6 deficiency in ADHD patients was found previously. Of note, we identified diverse virulence factor and antibiotic resistance from the gut microbiota of ADHD patients. The abundance of antibiotic resistance ontology ANT(9)-Ia positively correlated with the abundance of Prevotella_amnii , which was enriched in ADHD patients. Moreover, species-based bacterial markers were used to construct classifiers and achieved a higher AUC of 0.87 in C-ADHD vs. HC than that in ADHD vs. HC (AUC = 0.84).ConclusionsThese findings uncover alterations in microbial composition in subgroup patients and provide potential biomarkers for diagnosis different symptomatic presentations for ADHD. Trial registration: ClinicalTrials.gov, NCT03447223. Registered 27 February 2018, https://clinicaltrials.gov/ct2/show/NCT03447223?term=03447223&amp;draw=2&amp;rank=1

Neurofibromatosis type1 (NF1) is an autosomal dominant disorder caused by mutations in the NF1gene. Although congenital pseudarthrosis of the tibia (CPT) has frequently been associated with NF1, the underlying molecular mechanism of CPT in these NF1 patients is yet ill-understood. The aim of the present study was to detect NF1 mutations from genomic DNA and to harbor variants associated with CPT in NF1 patients. Whole-exome sequencing was first carried out with samples from two patients with CPT in one NF1 family, and a novel mutation c.2324A&amp;gt;G (p.E775G) in NF1 gene was identified. Additionally, a missense variant c.455C&amp;gt;T (p.P152L) in BCOR gene completely co-segregated with the CPT phenotype within this family. Subsequently, NF1 and NF2 genes in four other unrelated patients with both NF1 and CPT were screened using targeted sequencing. Four mutations in NF1 gene, including two known mutations (c.2288T&amp;gt;C/p.L763P, c.574 C&amp;gt;T/p.R192*) and two novel mutations (c.768delT/p.F256Lfs*25, c.2229_2230delTG/ p.V744Qfs*23) were detected. Further study confirmed that CPT was present in NF1 families, and NF1 mutations were closely associated with these complex phenotypes. Moreover, the data from the current study indicated that male gender might be a susceptibility factor for CPT in NF1. Therefore, we speculated that BCOR variants might be related to CPT phenotype among male NF1 patients.

Even frequently used in wheat breeding, we still have an insufficient understanding of the biology of the products via distant hybridization. In this study, a transcriptomic analysis was performed for six Triticum aestivum - Thinopyrum elongatum substitution lines in comparison with the host plants. All the six disomic substitution lines showed much stronger “transcriptomic-shock” occurred on alien genomes with 57.43–69.22% genes changed expression level but less on the recipient genome (2.19–8.97%). Genome-wide suppression of alien genes along chromosomes was observed with a high proportion of downregulated genes (39.69–48.21%). Oppositely, the wheat recipient showed genome-wide compensation with more upregulated genes, occurring on all chromosomes but not limited to the homeologous groups. Moreover, strong co-upregulation of the orthologs between wheat and Thinopyrum sub-genomes was enriched in photosynthesis with predicted chloroplastic localization, which indicates that the compensation happened not only on wheat host genomes but also on alien genomes.

Table S2. Data production, quality control, assembly result and gene prediction resulted from fecal metagenomic sequencing analysis. Table S3. Taxonomic profiles of fecal microbiota in NMS and control groups at phylum level. Table S4. Taxonomic profiles of fecal microbiota in NMS and control groups at genus level. Table S5. Taxonomic profiles of fecal microbiota in NMS and control groups at species level. Table S6. Correlation between species and saturated long-chain fatty acids determined by fecal metagenomic and metabolomic analyses. Table S7. Identified KOs involved in fatty acid synthesis and degradation. Table S8. Data production and quality control of fecal samples from 16s rRNA amplicon sequencing analysis. Table S9. Taxonomic changes at genus level between colonized GF rats and donors. (XLSX 73Â kb)

Additional file of A sequence-based genetic linkage map as a reference for Brassica rapa pseudochromosome assembly

Additional file 1:Details of the 507 sequence-based markers on the RCZ16_DH map, and information relating to anchored scaffolds using the RCZ16_DH map and the other three publicly available genetic linkage maps. (XLS 154 KB)

Additional file 2: Table S1. The comparison of [AT] values across ploymorphic sites among bread wheat and its wild progenitors. Table S2. Expression of candidate genes within qATD-3A and qATD-7D.

Abstract Background: Prolamins, unique to Gramineae (grasses), play a key role in the human diet. Thinopyrum elongatum (also known as tall wheatgrass, rush wheatgrass, or Eurasian quackgrass) of Elytrigia is genetically well-characterized, but little is known about its prolamin genes and the relationships with homologous loci in the Triticum genus . Results: In this study, a total of 19 α-gliadin, 9 γ-gliadin, 19 ω-gliadin, 2 high-molecular-weight glutenin subunit (HMW-GS), and 5 low-molecular-weight glutenin subunit (LMW-GS) genes in the Th. elongatum genome were annotated. The transcriptome data of Th. elongatum exhibited differential expression in quantity and pattern in the same subfamily or different subfamilies. In addition, microsynteny and phylogenetic analysis revealed dynamic changes of prolamin gene region and genetic affinities among Th. elongatum , T. aestivum , T. urartu , and Aegilops tauschii . The E genome, like the B genome, only contained DQ8-glia-α1/DQ8.5-glia-α1, which provided a theoretical basis for the study of celiac disease (CD). Dough rheological properties of T. aestivum - Th. elongatum disomic substitution (DS) lines 1E(1A), 1E(1D), and 3E(3A) showed much higher peak height values than that of their parent. Conclusions: Overall, this study provides a comprehensive overview of the prolamin gene superfamily in Th. elongatum , and suggests a promising use of this species in the generation of improved wheat breeds intended for the human diet.

Additional file of A sequence-based genetic linkage map as a reference for Brassica rapa pseudochromosome assembly

Additional file 1: Table S1. Prolamin genes in Th. elongatum genome. Table S2. Error correction of prolamin gene annotations in T. aestivum, Ae. tauschii and T. urartu. Table S3. Coding sequences for the prolamin genes in the four studied species. Table S4. Molecular characteristics of prolamin genes. Table S5. The distribution of CD epitopes in the genomes of T. aestivum, T. urartu, Ae. tauchii and Th. elongatum. Table S6. Transcriptome data of Th. elongatum at different development stages.